NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922) | NCT03107988 | Trialant
NCT03107988
Sponsor
New Approaches to Neuroblastoma Therapy Consortium
Status
Completed
Last Update Posted
Sep 15, 2025Actual
Enrollment
65Actual
Phase
Phase 1
Conditions
Neuroblastoma
Interventions
Lorlatinib
Cyclophosphamide
Topotecan
Filgrastim/pegfilgrastim
Countries
United States
Canada
France
United Kingdom
Protocol Section
Identification Module
NCT ID
NCT03107988
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
NANT2015-02
Secondary IDs
Not provided
Brief Title
NANT 2015-02: A Phase 1 Study of Lorlatinib (PF-06463922)
Official Title
Phase 1 Study of Lorlatinib (PF-06463922), an Oral Small Molecule Inhibitor of ALK/ROS1, for Patients With ALK-Driven Relapsed or Refractory Neuroblastoma
Acronym
Not provided
Organization
New Approaches to Neuroblastoma Therapy ConsortiumOTHER
Status Module
Record Verification Date
Sep 2025
Overall Recruitment Status or Expanded Access Status
Completed
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Not provided
Expanded Access Info
No
Start Date
Sep 5, 2017Actual
Primary Completion Date
Aug 22, 2024Actual
Completion Date
Jan 31, 2025Actual
First Submitted Date
Mar 21, 2017
First Submission Date that Met QC Criteria
Apr 4, 2017
First Posted Date
Apr 11, 2017Actual
Results Waived
Not provided
Results First Submitted Date
Jul 10, 2025
Results First Submitted that Met QC Criteria
Sep 11, 2025
Results First Posted Date
Sep 15, 2025Actual
Certification/Extension (aka Delayed Results) First Submitted Date
Not provided
Certification/Extension First Submitted that Passed QC Review
Not provided
Certification/Extension First Posted Date
Not provided
Last Update Submitted Date
Sep 11, 2025
Last Update Posted Date
Sep 15, 2025Actual
Sponsor/Collaborators Module
Responsible Party, by Official Title
Sponsor
Lead Sponsor
New Approaches to Neuroblastoma Therapy ConsortiumOTHER
Collaborators
Name
Class
Pfizer
INDUSTRY
University of Southern California
OTHER
Solving Kids' Cancer US/EU
UNKNOWN
Children's Neuroblastoma Cancer Foundation
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Yes
Is FDA Regulated Device
No
Is Unapproved Device
Not provided
Pediatric Postmarket Surveillance of a Device Product
Not provided
Product Exported from US
Not provided
FDAAA801 Violation
Not provided
Description Module
Brief Summary
Lorlatinib is a novel inhibitor across ALK variants, including those resistant to crizotinib. In this first pediatric phase 1 trial of lorlatinib, the drug will be utilized as a single agent and in combination with chemotherapy in patients with relapsed/refractory neuroblastoma. The dose escalation phase of this study (Cohort A1) uses a traditional Phase I 3+3 design. Once a recommended phase 2 pediatric dose is identified, an expansion cohort of 6 patients (Cohort B1), within which ALKi naïve patients will be prioritized, will be initiated. Parallel cohorts will be initiated in adults or patients with large BSA (Cohort A2) and in combination with chemotherapy upon establishing RP2D (Cohort B2).
Detailed Description
Lorlatinib is a novel inhibitor across ALK variants, including those resistant to crizotinib. An adult phase 1 study established an RP2D of 100mg QD for lorlatinib. In this first pediatric phase 1 trial of lorlatinib, the drug will be utilized as a single agent and in combination with chemotherapy in patients with relapsed/refractory neuroblastoma. The dose escalation phase of this study (Cohort A1) uses a traditional Phase I 3+3 design. Once a recommended phase 2 pediatric dose is identified, an expansion cohort of 6 patients (Cohort B1), within which ALKi naïve patients will be prioritized, will be initiated. Parallel cohorts will be initiated in adults or patients with large BSA (Cohort A2) and in combination with chemotherapy upon establishing RP2D (Cohort B2).
Lorlatinib will be administered orally via tablets or via oral dispersion if patient is unable to swallow tablets whole
All patients will participate in mandatory pharmacokinetic testing.
Conditions Module
Conditions
Neuroblastoma
Keywords
Not provided
Design Module
Study Type
Interventional
Number of References to an Expanded Access Study
Not provided
Expanded Access Types
Not provided
Patient Registry
Not provided
Target Follow-Up Duration
Not provided
Phases
Phase 1
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
65Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Cohort A1 DL1
Experimental
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 45 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Drug: Lorlatinib
Cohort A2 DL 3A
Experimental
Lorlatinib will be given at 100 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Drug: Lorlatinib
Cohort B2 DL4B
Experimental
Lorlatinib will be given orally once daily continuously for 28 days at 95mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Drug: Lorlatinib
Drug: Cyclophosphamide
Drug: Topotecan
Drug: Filgrastim/pegfilgrastim
Cohort A1 DL2
Experimental
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 60 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Drug: Lorlatinib
Cohort A1 DL3
Experimental
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Lorlatinib
Drug
Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cohort A1 DL1
Cohort A1 DL2
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
MTD/RP2D Determination A1
Proportion of patients with course 1 DLT and/or course 2 neuropsychological DLT in cohort A1
All toxicities from enrollment until completion of course 2 (Day 56)
MTD/RP2D Determination A2
Proportion of patients with course 1 DLT and/or course 2 neuropsychological DLT in cohort A2
All toxicities from enrollment until completion of course 2 (Day 56)
MTD/RP2D Determination B2
Proportion of patients with course 1 DLT in cohort B2
All toxicities from enrollment until completion of course 1 (Day 28)
Describe Non-Hematological Toxicities (A1 and B1)
Proportion of patients with any grade 3 or greater non-hematological toxicities on any course in A1 and B1
All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
Describe Hematological Toxicities (A1 and B1)
Proportion of patients with any grade 3 or greater hematological toxicities on any course in A1 and B1
All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
Describe Non-Hematological Toxicities (A2)
Proportion of patients with any grade 3 or greater non-hematological toxicities in A2
All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
Describe Hematological Toxicities (A2)
Secondary Outcomes
Measure
Description
Time Frame
Pharmacokinetics A1 and B1-Steady State AUC
Steady State AUC for lorlatinib in patients in cohort A1 and B1
Day 1 through Day 15 (0, 1, 2, 24, 360, 361, 362, 364, 366 hours post-initial dose)
Pharmacokinetics A2-Steady State AUC
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
Inclusion Criteria:
1) Patients are required to have an activating ALK aberration in their tumor detected by certified assay (i.e. CLIA in the US.) prior to registration. The report from this test is required to be submitted for eligibility. Patients with at least one of the following genetic features in their tumor will be considered to have an activating ALK aberration:
1. An ALK activating mutation; 2. ALK amplification (> 10 signals of the ALK gene); 3. Presence of any ALK fusion protein that arises from a chromosomal translocation 2) Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
3) Patients must have a history of high-risk neuroblastoma according to COG risk classification at the time of study registration. Patients who were initially considered low or intermediate-risk, but then reclassified as high-risk are also eligible.
4) All patients must have at least one of the following
a) Recurrent/progressive disease: after the diagnosis of high risk neuroblastoma at any time prior to enrollment regardless of response to frontline therapy b) No prior history of recurrent/progressive disease since the diagnosis of high risk neuroblastoma b1) Refractory disease- a best overall response of no response/stable disease since diagnosis of high risk neuroblastoma and at least 4 cycles of induction therapy. No prior history of recurrent/progressive disease since the diagnosis of high risk neuroblastoma.
b2) Persistent disease- a best overall response of no partial response since diagnosis of high risk neuroblastoma and at least 4 cycles of induction therapy. No prior history of recurrent/progressive disease since the diagnosis of high risk neuroblastoma.
5) Patients must have at least ONE of the following (lesions may have received prior radiation therapy as long as they meet the other criteria listed below):
For recurrent/progressive or refractory disease, at least one MIBG avid bone site.
For persistent disease, if a patient has 3 or more MIBG avid lesions, then no biopsy is required. If a patients has only 1 or 2 MIBG avid bone lesion sites then biopsy confirmation of neuroblastoma or ganglioneuroblastoma in at least one MIBG avid site present at the time of enrollment is required to be obtained at any time point prior to enrollment.
For MIBG non-avid tumors, patients must have at least one FDG avid site and a biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma at any time prior to enrollment from at least one FDG-avid site.
6) Any amount of neuroblastoma tumor cells in the bone marrow done at the time of study enrollment based on routine morphology with or without immunocytochemistry in at least one sample from bilateral aspirates and biopsies.
7) At least one soft tissue lesion that meets criteria for a TARGET lesion as defined by:
SIZE: Lesion can be accurately measured in at least one dimension with a longest diameter ≥ 10 mm, or for lymph nodes ≥ 15 mm on short axis. Lesions meeting size criteria will be considered measurable.
In addition to size, a lesion needs to meet one of the following criteria except for patients with parenchymal CNS lesions which only need to meet size criteria:
b1) MIBG avid. For patients with recurrent/progressive or refractory disease, no biopsy is required. For patients with persistent disease only: If a patient has only 1 or 2 MIBG avid lesions sites, then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one MIBG avid site present at time of enrollment is required to be obtained. If a patient has 3 or more MIBG avid lesions, then no biopsy is required.
b2) MIBG non avid tumors: Patients must have at least one FDG avid site and biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one FDG-PET avid site present at the time of enrollment.
8) At least one non-target soft tissue lesion that is not measurable, but had a biopsy positive for neuroblastoma and/or ganglioneuroblastoma or is MIBG avid at any time prior to enrollment.
9) Patients must have a life expectancy of at least 12 weeks and a Lansky (≤16 years) or Karnofsky (>16 years) score of at least 50.
10) Prior Therapy
Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study registration.
Patients must not have received the therapies indicated below after disease evaluation or within the specified time period prior to registration on this study as follows:
1. Myelosuppressive chemotherapy: must not have received within 2 weeks prior to registration.
2. Biologic anti-neoplastics- agents not known to be associated with reduced platelet or ANC counts (including retinoids): must not have received within 7 days prior to registration.
3. Monoclonal antibodies: must have received last dose at least 7 days or 3 half-lives whichever is longer, but no longer than 30 days (with recovery of any associated toxicities), prior to protocol therapy.
4. Cellular Therapy (e.g. modified T cells, NK cells, dentritic cells etc.): must not have received within 3 weeks and resolution of all toxicities.
5. Radiation: must not have received small port radiation within 7 days prior to registration.
6. Hematopoietic Stem Cell Transplant: 7. IVIG 11) All patients must have adequate organ function defined as:
- Hematological Function:
1. Absolute Phagocyte count (APC= neutrophils and monocytes): ≥ 1000/µL
2. Absolute Neutrophil count: ≥750/µL
3. Absolute Lymphocyte count ≥ 500/µL
4. Platelet count: ≥ 50,000/µL (A1, A2, and B1); ≥ 75,000/µL (B2), transfusion independent (no platelet transfusions within 1 week)
5. Hemoglobin ≥ 10 g/dL (may transfuse)
6. Patients with known bone marrow metastatic disease will be eligible for study as long as they meet hematologic function criteria above.
- Renal Function: Age-adjusted serum creatinine ≤ to 1.5 x normal for age/gender OR creatinine clearance or GFR greater than or equal to 60 cc/min/1.73m2
- Liver Function: Total bilirubin ≤ 1.5 x normal for age, AND SGPT (ALT) 135 and SGOT (AST) ≤ 3 x upper limit of normal. Sinusoidal obstruction syndrome (SOS) if present, must be stable or improving clinically
- Cardiac Function: Normal ejection fraction documented by either echocardiogram or radionuclide MUGA evaluation OR Normal fractional shortening documented by echocardiogram
- Pulmonary Function: No dyspnea at rest, no oxygen requirement.
Neuropsychological Function: Patients must exhibit ≤ grade 1 as defined by CTCAE V4 of nervous system disorders and psychiatric disorders 12) Reproductive Status: All post-menarchal females must have a negative beta-HCG. Males and females of reproductive age and childbearing potential must use effective contraception for the duration of their participation.
13) Patients with other ongoing serious medical issues must be approved by the study chair prior to registration.
14) Prior ALK inhibitor treatment- patients must not have been previously treated with lorlatinib. Prior therapy with other ALK inhibitors is allowed.
15) Concomitant Therapy Restrictions:
Patients may not receive any other anti-cancer agents or radiotherapy while on protocol therapy.
Patient must not be receiving chronic systemic corticosteroids at doses greater than physiologic dosing (inhaled corticosteroids acceptable)
CYP34A inhibitors
CYP34A inducers
CYP34A substrates
Exclusion Criteria:
- Pregnancy, breast feeding, or unwillingness to use effective contraception during the study.
Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
Patients with disease of any major organ system that would compromise their ability to withstand therapy.
Patients who have received prior allogeneic stem cell transplant
Patients who are on hemodialysis.
Patients with an active or uncontrolled infection.
Known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C.
Patient with known history of acute or chronic severe psychiatric disorders
Patient with current history of suicidal ideation and history of suicide attempt in their lifetime
Patient declines participation in NANT 2004-05, the NANT Biology Study
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
1 Year
Maximum Age
99 Years
Standard Ages
ChildAdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Yael Mosse, MD
Children's Hospital of Philadelphia
Study Chair
Locations
Facility
Status
City
State
ZIP
Country
Contacts
Children's Hospital Los Angeles
Los Angeles
California
90027-0700
United States
UCSF Helen Diller Family Comprehensive Cancer Center
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 45 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Periods
Title
Milestones
Reasons Not Completed
Overall Study
Type
Comment
Milestone Data
STARTED
Baseline Characteristics Module
Baseline Analysis Population Description
Outcome Measures Module
Outcome Measures
Adverse Events Module
Frequency Threshold
5
More Info Module
Limitations and Caveats
Not provided
Annotation Section
No data available
No data is available for this block.
Document Section
Large Document Module
Document Has No Statistical Analysis Plan (SAP)
Not provided
Uploaded Document Information
Type
Includes Protocol
Includes SAP
Includes ICF
Document Label
Document Date
Document Uploaded Date
Document File Name
Prot_SAP_ICF
Yes
Yes
Yes
Study Protocol, Statistical Analysis Plan, and Informed Consent Form
May 6, 2022
Derived Section
Miscellaneous Info Module
Version Holder
Jul 10, 2026
Removed Countries
Not provided
Submission Tracking
No data available
No data is available for this block.
Condition Browse Module
MeSH Terms
Intervention Browse Module
MeSH Terms
UNKNOWN
The Band of Parents
UNKNOWN
The Evan Foundation
OTHER
Wade's Army
UNKNOWN
Ronan Thompson Foundation
UNKNOWN
The Catherine Elizabeth Blair Memorial Foundation
UNKNOWN
Cookies for Kids' Cancer
OTHER
Non-Randomized
Intervention Model
Parallel Assignment
Intervention Model Description
Not provided
Primary Purpose
Treatment
Observational Model
Not provided
Time Perspective
Not provided
Masking Info
Masking
None (Open Label)
Masking Description
Not provided
Who Masked
Not provided
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 75 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Drug: Lorlatinib
Cohort A1 DL4
Experimental
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 95 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Drug: Lorlatinib
Cohort A1 DL5
Experimental
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Drug: Lorlatinib
Cohort A2 DL4A
Experimental
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Drug: Lorlatinib
Cohort B2 DL5B
Experimental
Lorlatinib will be given orally once daily continuously for 28 days at 115mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Drug: Lorlatinib
Drug: Cyclophosphamide
Drug: Topotecan
Drug: Filgrastim/pegfilgrastim
Cohort B2 DL3A
Experimental
Lorlatinib will be given orally once daily continuously for 28 days at 100mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Drug: Lorlatinib
Drug: Cyclophosphamide
Drug: Topotecan
Drug: Filgrastim/pegfilgrastim
Cohort B2 DL4A
Experimental
Lorlatinib will be given orally once daily continuously for 28 days at 150mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Drug: Lorlatinib
Drug: Cyclophosphamide
Drug: Topotecan
Drug: Filgrastim/pegfilgrastim
Cohort B1 DL5
Experimental
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Drug: Lorlatinib
Cohort A2 DL4A Expansion
Experimental
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Drug: Lorlatinib
Cohort A1 DL3
Cohort A1 DL4
Cohort A1 DL5
Cohort A2 DL 3A
Cohort A2 DL4A
Cohort A2 DL4A Expansion
Cohort B1 DL5
Cohort B2 DL3A
Cohort B2 DL4A
Cohort B2 DL4B
Cohort B2 DL5B
PF06463922
Cyclophosphamide
Drug
Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Cohort B2 DL3A
Cohort B2 DL4A
Cohort B2 DL4B
Cohort B2 DL5B
Cytoxan
Topotecan
Drug
Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Cohort B2 DL3A
Cohort B2 DL4A
Cohort B2 DL4B
Cohort B2 DL5B
SKF-104864,Hycamtin®
Filgrastim/pegfilgrastim
Drug
Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
Cohort B2 DL3A
Cohort B2 DL4A
Cohort B2 DL4B
Cohort B2 DL5B
Proportion of patients with any grade 3 or greater hematological toxicities in A2
All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
Describe Non-Hematological Toxicities (B2)
Proportion of patients with any grade 3 or greater non-hematological toxicities in B2
All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
Describe Hematological Toxicities (B2)
Proportion of patients with any grade 3 or greater hematological toxicities in B2
All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
Steady State AUC for lorlatinib in patients in cohort A2
Day 1 through Day 15 (0, 1, 2, 24, 360, 361, 362, 364, 366 hours post-initial dose)
Pharmacokinetics B2-Steady State AUC
Steady State AUC for lorlatinib in patients in cohort B2
Day 1 through Day 15 (0, 1, 2, 24, 360, 361, 362, 364, 366 hours post-initial dose)
Overall Response A1 and B1
Proportion of patients evaluable for response with a best overall response of CR/CR-MD/PR for patients in cohort A1 and B1
From Day 1 of protocol therapy through 30 days following end of protocol therapy, an average of 10 months
Overall Response A2
Proportion of patients evaluable for response with a best overall response of CR/CR-MD/PR for patients in cohort A2
From Day 1 of protocol therapy through 30 days following end of protocol therapy, an average of 10 months
Overall Response B2
Proportion of patients evaluable for response with a best overall response of CR/CR-MD/PR for patients in cohort B2
From Day 1 of protocol therapy through 30 days following end of protocol therapy, an average of 10 months
Pharmacokinetics A1 and B1-Cmax
Cmax for lorlatinib in patients in cohort A1 and B1
Day 15
Pharmacokinetics A2-Cmax
Cmax for lorlatinib in patients in cohort A2
Day 15
Pharmacokinetics B2-Cmax
Cmax for lorlatinib in patients in cohort B2
Day 15
San Francisco
California
94143
United States
Children Hospital of Colorado
Aurora
Colorado
80045
United States
Children's Healthcare of Atlanta
Atlanta
Georgia
30322
United States
University of Chicago, Comer Children's Hospital
Chicago
Illinois
60637
United States
Childrens Hospital Boston, Dana-Farber Cancer Institute.
Boston
Massachusetts
02115
United States
C.S Mott Children's Hospital
Ann Arbor
Michigan
48109
United States
Children's Hospital of Philadelphia
Philadelphia
Pennsylvania
19104-4318
United States
Cook Children's Healthcare System
Fort Worth
Texas
76104
United States
Children's Hospital and Regional Medical Center - Seattle
Seattle
Washington
98105
United States
Hospital for Sick Children
Toronto
Ontario
M5G 1X8
Canada
Institut Curie
Paris
Cedex
05
France
Royal Marsden Hospital
Sutton
Surrey
SM25NG
United Kingdom
Derived
Baranowska-Kortylewicz J, Kortylewicz ZP, McIntyre EM, Sharp JG, Coulter DW. Multifarious Functions of Butyrylcholinesterase in Neuroblastoma: Impact of BCHE Deletion on the Neuroblastoma Growth In Vitro and In Vivo. J Pediatr Hematol Oncol. 2022 Aug 1;44(6):293-304. doi: 10.1097/MPH.0000000000002285. Epub 2021 Sep 6.
FG001
Cohort A1 DL2
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 60 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
FG002
Cohort A1 DL3
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 75 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
FG003
Cohort A1 DL4
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 95 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
FG004
Cohort A1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
FG005
Cohort A2 DL 3A
Lorlatinib will be given at 100 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
FG006
Cohort A2 DL4A
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
FG007
Cohort A2 DL4A Expansion
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
FG008
Cohort B1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
FG009
Cohort B2 DL4B
Lorlatinib will be given orally once daily continuously for 28 days at 95mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
FG010
Cohort B2 DL5B
Lorlatinib will be given orally once daily continuously for 28 days at 115mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
FG011
Cohort B2 DL3A
Lorlatinib will be given orally once daily continuously for 28 days at 100mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
FG012
Cohort B2 DL4A
Lorlatinib will be given orally once daily continuously for 28 days at 150mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
FG0003 subjects
FG0013 subjects
FG0023 subjects
FG00310 subjects
FG0046 subjects
FG0056 subjects
FG0066 subjects
FG0074 subjects
FG0086 subjects
FG0093 subjects
FG01013 subjects
FG0111 subjects
FG0121 subjects
COMPLETED
FG0002 subjects
FG0011 subjects
FG0021 subjects
FG0034 subjects
FG0045 subjects
FG0054 subjects
FG0066 subjects
FG0073 subjects
FG0085 subjects
FG0092 subjects
FG0109 subjects
FG0111 subjects
FG0121 subjects
NOT COMPLETED
FG0001 subjects
FG0012 subjects
FG0022 subjects
FG0036 subjects
FG0041 subjects
FG0052 subjects
FG0060 subjects
FG0071 subjects
FG0081 subjects
FG0091 subjects
FG0104 subjects
FG0110 subjects
FG0120 subjects
Type
Comment
Reasons
Adverse Event
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0031 subjects
FG0040 subjects
FG0051 subjects
FG0060 subjects
FG0071 subjects
FG0080 subjects
FG0090 subjects
FG0100 subjects
FG0110 subjects
FG0120 subjects
Disease Progression or Relapse
FG0001 subjects
FG0012 subjects
FG0022 subjects
FG0035 subjects
FG004
Ineligible
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
65 patients are included in the initial participant flow as 65 patients were enrolled on this protocol. However, 1 patient was determined to be ineligible prior to start of protocol therapy. The 64 patients included in the baseline analysis population represent all eligible enrolled patients on this protocol.
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Cohort A1 DL1
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 45 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
BG001
Cohort A1 DL2
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 60 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
BG002
Cohort A1 DL3
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 75 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
BG003
Cohort A1 DL4
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 95 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
BG004
Cohort A1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
BG005
Cohort A2 DL 3A
Lorlatinib will be given at 100 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
BG006
Cohort A2 DL4A
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
BG007
Cohort A2 DL4A Expansion
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
BG008
Cohort B1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
BG009
Cohort B2 DL4B
Lorlatinib will be given orally once daily continuously for 28 days at 95mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
BG010
Cohort B2 DL5B
Lorlatinib will be given orally once daily continuously for 28 days at 115mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
BG011
Cohort B2 DL3A
Lorlatinib will be given orally once daily continuously for 28 days at 100mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
BG012
Cohort B2 DL4A
Lorlatinib will be given orally once daily continuously for 28 days at 150mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
BG013
Total
Total of all reporting groups
Denominators
Units
Counts
Participants
BG0003
BG0013
BG0023
BG00310
BG0046
BG0056
BG0066
BG0074
BG0085
BG0093
BG01013
BG0111
BG0121
BG01364
Baseline Measures
Title
Description
Population Description
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Denominator Units Selected
Denominators
Classes
Age, Categorical
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0003
BG0013
BG0023
BG003
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0002
BG0012
BG002
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG002
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG002
Type
Title
Description
Population Description
Reporting Status
Anticipated Posting Date
Parameter Type
Dispersion Type
Unit of Measure
Calculate Percentage
Time Frame
Units Analyzed
Denominator Units Selected
Arm/Group Information
Denominators
Classes
Analyses
Primary
MTD/RP2D Determination A1
Proportion of patients with course 1 DLT and/or course 2 neuropsychological DLT in cohort A1
Posted
Count of Participants
Participants
All toxicities from enrollment until completion of course 2 (Day 56)
ID
Title
Description
OG000
Cohort A1 DL1
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 45 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG001
Cohort A1 DL2
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 60 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG002
Cohort A1 DL3
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 75 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG003
Cohort A1 DL4
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 95 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG004
Cohort A1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG003
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG003
Primary
MTD/RP2D Determination A2
Proportion of patients with course 1 DLT and/or course 2 neuropsychological DLT in cohort A2
Posted
Count of Participants
Participants
All toxicities from enrollment until completion of course 2 (Day 56)
ID
Title
Description
OG000
Cohort A2 DL 3A
Lorlatinib will be given at 100 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG001
Cohort A2 DL4A
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG002
Cohort A2 DL4A Expansion
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Primary
MTD/RP2D Determination B2
Proportion of patients with course 1 DLT in cohort B2
Posted
Count of Participants
Participants
All toxicities from enrollment until completion of course 1 (Day 28)
ID
Title
Description
OG000
Cohort B2 DL4B
Lorlatinib will be given orally once daily continuously for 28 days at 95mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG001
Cohort B2 DL5B
Lorlatinib will be given orally once daily continuously for 28 days at 115mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
Primary
Describe Non-Hematological Toxicities (A1 and B1)
Proportion of patients with any grade 3 or greater non-hematological toxicities on any course in A1 and B1
Posted
Count of Participants
Participants
All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
ID
Title
Description
OG000
Cohort A1 DL1
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 45 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG001
Cohort A1 DL2
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 60 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG002
Cohort A1 DL3
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 75 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Primary
Describe Hematological Toxicities (A1 and B1)
Proportion of patients with any grade 3 or greater hematological toxicities on any course in A1 and B1
Posted
Count of Participants
Participants
All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
ID
Title
Description
OG000
Cohort A1 DL1
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 45 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG001
Cohort A1 DL2
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 60 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG002
Cohort A1 DL3
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 75 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Primary
Describe Non-Hematological Toxicities (A2)
Proportion of patients with any grade 3 or greater non-hematological toxicities in A2
Posted
Count of Participants
Participants
All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
ID
Title
Description
OG000
Cohort A2 DL 3A
Lorlatinib will be given at 100 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG001
Cohort A2 DL4A
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG002
Cohort A2 DL4A Expansion
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Primary
Describe Hematological Toxicities (A2)
Proportion of patients with any grade 3 or greater hematological toxicities in A2
Posted
Count of Participants
Participants
All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
ID
Title
Description
OG000
Cohort A2 DL 3A
Lorlatinib will be given at 100 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG001
Cohort A2 DL4A
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG002
Cohort A2 DL4A Expansion
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Primary
Describe Non-Hematological Toxicities (B2)
Proportion of patients with any grade 3 or greater non-hematological toxicities in B2
Posted
Count of Participants
Participants
All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
ID
Title
Description
OG000
Cohort B2 DL4B
Lorlatinib will be given orally once daily continuously for 28 days at 95mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG001
Cohort B2 DL5B
Primary
Describe Hematological Toxicities (B2)
Proportion of patients with any grade 3 or greater hematological toxicities in B2
Posted
Count of Participants
Participants
All toxicities from enrollment through 30 days following end of protocol therapy, an average of 10 months
ID
Title
Description
OG000
Cohort B2 DL4B
Lorlatinib will be given orally once daily continuously for 28 days at 95mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG001
Cohort B2 DL5B
Secondary
Pharmacokinetics A1 and B1-Steady State AUC
Steady State AUC for lorlatinib in patients in cohort A1 and B1
No AUCtau is included for patients in Cohort B1DL5 as they do not have the sufficient samples at the necessary time points to calculate a terminal half-life so any estimation would not be reliable.
Posted
Median
Full Range
hours*ng/mL
Day 1 through Day 15 (0, 1, 2, 24, 360, 361, 362, 364, 366 hours post-initial dose)
ID
Title
Description
OG000
Cohort A1 DL1
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 45 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG001
Cohort A1 DL2
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 60 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG002
Cohort A1 DL3
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 75 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Secondary
Pharmacokinetics A2-Steady State AUC
Steady State AUC for lorlatinib in patients in cohort A2
Posted
Median
Full Range
hours*ng/mL
Day 1 through Day 15 (0, 1, 2, 24, 360, 361, 362, 364, 366 hours post-initial dose)
ID
Title
Description
OG000
Cohort A2 DL 3A
Lorlatinib will be given at 100 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG001
Cohort A2 DL4A
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG002
Cohort A2 DL4A Expansion
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Secondary
Pharmacokinetics B2-Steady State AUC
Steady State AUC for lorlatinib in patients in cohort B2
No AUCtau is included for patients in Cohort B2 DL4B or Cohort B2 DL3A as they do not have the sufficient samples at the necessary time points to calculate a terminal half-life so any estimation would not be reliable.
Posted
Median
Full Range
hours*ng/mL
Day 1 through Day 15 (0, 1, 2, 24, 360, 361, 362, 364, 366 hours post-initial dose)
ID
Title
Description
OG000
Cohort B2 DL4B
Lorlatinib will be given orally once daily continuously for 28 days at 95mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
Secondary
Overall Response A1 and B1
Proportion of patients evaluable for response with a best overall response of CR/CR-MD/PR for patients in cohort A1 and B1
Posted
Count of Participants
Participants
From Day 1 of protocol therapy through 30 days following end of protocol therapy, an average of 10 months
ID
Title
Description
OG000
Cohort A1 DL1
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 45 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG001
Cohort A1 DL2
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 60 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG002
Cohort A1 DL3
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 75 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Secondary
Overall Response A2
Proportion of patients evaluable for response with a best overall response of CR/CR-MD/PR for patients in cohort A2
Posted
Count of Participants
Participants
From Day 1 of protocol therapy through 30 days following end of protocol therapy, an average of 10 months
ID
Title
Description
OG000
Cohort A2 DL 3A
Lorlatinib will be given at 100 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG001
Cohort A2 DL4A
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG002
Cohort A2 DL4A Expansion
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Secondary
Overall Response B2
Proportion of patients evaluable for response with a best overall response of CR/CR-MD/PR for patients in cohort B2
Posted
Count of Participants
Participants
From Day 1 of protocol therapy through 30 days following end of protocol therapy, an average of 10 months
ID
Title
Description
OG000
Cohort B2 DL4B
Lorlatinib will be given orally once daily continuously for 28 days at 95mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG001
Cohort B2 DL5B
Secondary
Pharmacokinetics A1 and B1-Cmax
Cmax for lorlatinib in patients in cohort A1 and B1
Posted
Median
Full Range
ng/mL
Day 15
ID
Title
Description
OG000
Cohort A1 DL1
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 45 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG001
Cohort A1 DL2
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 60 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG002
Cohort A1 DL3
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 75 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Secondary
Pharmacokinetics A2-Cmax
Cmax for lorlatinib in patients in cohort A2
Posted
Median
Full Range
ng/mL
Day 15
ID
Title
Description
OG000
Cohort A2 DL 3A
Lorlatinib will be given at 100 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG001
Cohort A2 DL4A
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG002
Cohort A2 DL4A Expansion
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Secondary
Pharmacokinetics B2-Cmax
Cmax for lorlatinib in patients in cohort B2
Posted
Median
Full Range
ng/mL
Day 15
ID
Title
Description
OG000
Cohort B2 DL4B
Lorlatinib will be given orally once daily continuously for 28 days at 95mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG001
Cohort B2 DL5B
Lorlatinib will be given orally once daily continuously for 28 days at 115mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
Time Frame
Timeframe from enrollment through 30 days following end of protocol therapy, an average of 10 months
Description
Not provided
All-Cause Mortality Comment
Not provided
Arm/Groups
ID
Title
Description
Deaths (Affected)
Deaths (At Risk)
Serious Events (Affected)
Serious Events (At Risk)
Other Events (Affected)
Other Events (At Risk)
EG000
Cohort A1 DL1
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 45 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
2
3
1
3
3
3
EG001
Cohort A1 DL2
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 60 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
3
3
1
3
3
3
EG002
Cohort A1 DL3
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 75 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
2
3
0
3
3
3
EG003
Cohort A1 DL4
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 95 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
9
10
3
10
9
10
EG004
Cohort A1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
3
6
2
6
6
6
EG005
Cohort A2 DL 3A
Lorlatinib will be given at 100 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
4
6
4
6
6
6
EG006
Cohort A2 DL4A
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
2
6
3
6
6
6
EG007
Cohort A2 DL4A Expansion
Lorlatinib will be given at 150 mg orally once daily continuously for 28 days. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
0
4
1
4
4
4
EG008
Cohort B1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
3
5
3
5
5
5
EG009
Cohort B2 DL4B
Lorlatinib will be given orally once daily continuously for 28 days at 95mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
2
3
3
3
3
3
EG010
Cohort B2 DL5B
Lorlatinib will be given orally once daily continuously for 28 days at 115mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
7
13
10
13
12
13
EG011
Cohort B2 DL3A
Lorlatinib will be given orally once daily continuously for 28 days at 100mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
0
1
1
1
1
1
EG012
Cohort B2 DL4A
Lorlatinib will be given orally once daily continuously for 28 days at 150mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
0
1
1
1
1
1
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anemia
Blood and lymphatic system disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG0031 affected10 at risk
EG0040 affected6 at risk
EG0050 affected6 at risk
EG0060 affected6 at risk
EG0070 affected4 at risk
EG0080 affected5 at risk
EG0090 affected3 at risk
EG0100 affected13 at risk
EG0111 affected1 at risk
EG0120 affected1 at risk
Febrile neutropenia
Blood and lymphatic system disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Blurred vision
Eye disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Diarrhea
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Duodenal obstruction
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Fever
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Flu like symptoms
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Multi-organ failure
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
TRANSFUSION-ASSOCIATED CIRCULATORY OVERLOAD
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
BILIARY OBSTRUCTION
Hepatobiliary disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
COVID 19
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Catheter related infection
Infections and infestations
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Flu like symptoms
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Lung infection
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Skin infection
Infections and infestations
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Cholesterol high
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Creatinine increased
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Platelet count decreased
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hyperglycemia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hyperkalemia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
PAPILLARY THYROID CARCINOMA
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Treatment related secondary malignancy
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Tumor pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Depressed level of consciousness
Nervous system disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Mania
Psychiatric disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Psychosis
Psychiatric disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Epistaxis
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hypoxia
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Pneumonitis
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Respiratory failure
Respiratory, thoracic and mediastinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Skin ulceration
Skin and subcutaneous tissue disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hypertension
Vascular disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Thromboembolic event
Vascular disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Anemia
Blood and lymphatic system disorders
Systematic Assessment
EG0001 affected3 at risk
EG0013 affected3 at risk
EG0021 affected3 at risk
EG0037 affected10 at risk
EG0043 affected6 at risk
EG0054 affected6 at risk
EG0064 affected6 at risk
EG0072 affected4 at risk
EG0083 affected5 at risk
EG0093 affected3 at risk
EG01012 affected13 at risk
EG0111 affected1 at risk
EG0121 affected1 at risk
Leukocytosis
Blood and lymphatic system disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Atrioventricular block first degree
Cardiac disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Palpitations
Cardiac disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Sinus bradycardia
Cardiac disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Sinus tachycardia
Cardiac disorders
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Ear pain
Ear and labyrinth disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hearing impaired
Ear and labyrinth disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected3 at risk
EG003
Tinnitus
Ear and labyrinth disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hypothyroidism
Endocrine disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
ABNORMAL EYE MOVEMENTS
Eye disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Blurred vision
Eye disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Conjunctivitis
Eye disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dry eye
Eye disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Eye pain
Eye disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Eyelid function disorder
Eye disorders
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Keratitis
Eye disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Photophobia
Eye disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
SUBCONJUNCTIVAL HEMORRHAGE
Eye disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
ANAL FISSURE
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Abdominal distension
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Abdominal pain
Gastrointestinal disorders
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Bloating
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Cheilitis
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Constipation
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dental caries
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Diarrhea
Gastrointestinal disorders
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected3 at risk
EG0022 affected3 at risk
EG003
Dry mouth
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dysphagia
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Enterocolitis
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Fecal incontinence
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Flatulence
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Gastroesophageal reflux disease
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Mucositis oral
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Nausea
Gastrointestinal disorders
Systematic Assessment
EG0002 affected3 at risk
EG0010 affected3 at risk
EG0021 affected3 at risk
EG003
Oral dysesthesia
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Oral hemorrhage
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Oral pain
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Pancreatitis
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Salivary duct inflammation
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Stomach pain
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Vomiting
Gastrointestinal disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected3 at risk
EG003
Chills
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Edema face
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Edema limbs
General disorders
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Fatigue
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Fever
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0012 affected3 at risk
EG0021 affected3 at risk
EG003
Flu like symptoms
General disorders
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Gait disturbance
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Infusion related reaction
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Irritability
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Localized edema
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Malaise
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Non-cardiac chest pain
General disorders
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Pain
General disorders
Systematic Assessment
EG0002 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Allergic reaction
Immune system disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected3 at risk
EG003
ASTROVIRUS
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Bladder infection
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
COVID 19
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Catheter related infection
Infections and infestations
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Cervicitis infection
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Flu like symptoms
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Lip infection
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Lung infection
Infections and infestations
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Nail infection
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Otitis externa
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Otitis media
Infections and infestations
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Papulopustular rash
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Paronychia
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Pharyngitis
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Sinusitis
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Skin infection
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Tooth infection
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Upper respiratory infection
Infections and infestations
Systematic Assessment
EG0001 affected3 at risk
EG0012 affected3 at risk
EG0021 affected3 at risk
EG003
Urinary tract infection
Infections and infestations
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Vaginal infection
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Vulval infection
Infections and infestations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Bruising
Injury, poisoning and procedural complications
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Fall
Injury, poisoning and procedural complications
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Postoperative hemorrhage
Injury, poisoning and procedural complications
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Activated partial thromboplastin time prolonged
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Alanine aminotransferase increased
Investigations
Systematic Assessment
EG0002 affected3 at risk
EG0013 affected3 at risk
EG0022 affected3 at risk
EG003
Alkaline phosphatase increased
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected3 at risk
EG003
Aspartate aminotransferase increased
Investigations
Systematic Assessment
EG0002 affected3 at risk
EG0013 affected3 at risk
EG0022 affected3 at risk
EG003
Blood bilirubin increased
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Cholesterol high
Investigations
Systematic Assessment
EG0003 affected3 at risk
EG0013 affected3 at risk
EG0023 affected3 at risk
EG003
Creatinine increased
Investigations
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
ELEVATED CRP
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
ELEVATED SED RATE
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Ejection fraction decreased
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Electrocardiogram QT corrected interval prolonged
Investigations
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
GGT increased
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
HYPERPHOSPHATEMIA
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hemoglobin increased
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
INCREASED UREA
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
LDH INCREASE
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Lipase increased
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Lymphocyte count decreased
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0021 affected3 at risk
EG003
Lymphocyte count increased
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
NAIL CHANGES
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
NEUTROPHIL COUNT INCREASED
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Neutrophil count decreased
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Pancreatic enzymes decreased
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Platelet count decreased
Investigations
Systematic Assessment
EG0001 affected3 at risk
EG0012 affected3 at risk
EG0022 affected3 at risk
EG003
Weight gain
Investigations
Systematic Assessment
EG0003 affected3 at risk
EG0013 affected3 at risk
EG0023 affected3 at risk
EG003
Weight loss
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
White blood cell decreased
Investigations
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0021 affected3 at risk
EG003
Anorexia
Metabolism and nutrition disorders
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Dehydration
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Glucose intolerance
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hypercalcemia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hyperglycemia
Metabolism and nutrition disorders
Systematic Assessment
EG0001 affected3 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Hyperkalemia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hypermagnesemia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected3 at risk
EG003
Hypernatremia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hypertriglyceridemia
Metabolism and nutrition disorders
Systematic Assessment
EG0003 affected3 at risk
EG0013 affected3 at risk
EG0023 affected3 at risk
EG003
Hyperuricemia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hypoalbuminemia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hypocalcemia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hypoglycemia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Hypokalemia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected3 at risk
EG003
Hypomagnesemia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected3 at risk
EG003
Hyponatremia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0021 affected3 at risk
EG003
Hypophosphatemia
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
INCREASED APPETITE
Metabolism and nutrition disorders
Systematic Assessment
EG0002 affected3 at risk
EG0012 affected3 at risk
EG0022 affected3 at risk
EG003
Iron overload
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
LDL DIRECT INCREASED
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Obesity
Metabolism and nutrition disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Arthralgia
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Back pain
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Bone pain
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0001 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Buttock pain
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
CRAMPS
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Chest wall pain
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Generalized muscle weakness
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Myalgia
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
PATELLAR SUBFIXATION
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Pain in extremity
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 affected3 at risk
EG0011 affected3 at risk
EG0020 affected3 at risk
EG003
Scoliosis
Musculoskeletal and connective tissue disorders
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
PAPILLARY THYROID CARCINOMA
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Treatment related secondary malignancy
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Systematic Assessment
EG0000 affected3 at risk
EG0010 affected3 at risk
EG0020 affected3 at risk
EG003
Tumor pain
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lorlatinib will be given orally once daily continuously for 28 days at 100mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG003
Cohort B2 DL4A
Lorlatinib will be given orally once daily continuously for 28 days at 150mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
Units
Counts
Participants
OG0003
OG00112
OG0021
OG0031
Title
Denominators
Categories
Title
Measurements
OG0000
OG0011
OG0020
OG0030
OG003
Cohort A1 DL4
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 95 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG004
Cohort A1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG005
Cohort B1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG00310
OG0046
OG0055
Title
Denominators
Categories
Title
Measurements
OG0003
OG0012
OG0021
OG0035
OG0046
OG0054
OG003
Cohort A1 DL4
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 95 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG004
Cohort A1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG005
Cohort B1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG00310
OG0046
OG0055
Title
Denominators
Categories
Title
Measurements
OG0000
OG0010
OG0020
OG0035
OG0042
OG0051
Units
Counts
Participants
OG0006
OG0016
OG0024
Title
Denominators
Categories
Title
Measurements
OG0006
OG0014
OG0022
Units
Counts
Participants
OG0006
OG0016
OG0024
Title
Denominators
Categories
Title
Measurements
OG0003
OG0011
OG0020
Lorlatinib will be given orally once daily continuously for 28 days at 115mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG002
Cohort B2 DL3A
Lorlatinib will be given orally once daily continuously for 28 days at 100mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG003
Cohort B2 DL4A
Lorlatinib will be given orally once daily continuously for 28 days at 150mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
Units
Counts
Participants
OG0003
OG00113
OG0021
OG0031
Title
Denominators
Categories
Title
Measurements
OG0003
OG00112
OG0021
OG0031
Lorlatinib will be given orally once daily continuously for 28 days at 115mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG002
Cohort B2 DL3A
Lorlatinib will be given orally once daily continuously for 28 days at 100mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG003
Cohort B2 DL4A
Lorlatinib will be given orally once daily continuously for 28 days at 150mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
Units
Counts
Participants
OG0003
OG00113
OG0021
OG0031
Title
Denominators
Categories
Title
Measurements
OG0003
OG00112
OG0021
OG0031
OG003
Cohort A1 DL4
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 95 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG004
Cohort A1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG005
Cohort B1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Units
Counts
Participants
OG0002
OG0011
OG0021
OG0036
OG0043
OG0051
Title
Denominators
Categories
Title
Measurements
OG0001872(1074.93 to 2669.08)
OG0012663.49(2663.49 to 2663.49)
OG0022084.81(2084.81 to 2084.81)
OG0037431.06(3021.81 to 8906.31)
OG0045655.05(4724.92 to 10910.87)
OG005NA(NA to NA)No AUCtau is included for patients in Cohort B1DL5 as they do not have the sufficient samples at the necessary time points to calculate a terminal half-life so any estimation would not be reliable.
Units
Counts
Participants
OG0002
OG0013
OG0023
Title
Denominators
Categories
Title
Measurements
OG0009217.85(7267.6 to 11168.1)
OG0014492.92(3993.55 to 5139)
OG0025383.5(4629.88 to 5747.95)
OG001
Cohort B2 DL5B
Lorlatinib will be given orally once daily continuously for 28 days at 115mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG002
Cohort B2 DL3A
Lorlatinib will be given orally once daily continuously for 28 days at 100mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG003
Cohort B2 DL4A
Lorlatinib will be given orally once daily continuously for 28 days at 150mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
Units
Counts
Participants
OG0002
OG0017
OG0021
OG0031
Title
Denominators
Categories
Title
Measurements
OG000NA(NA to NA)No AUCtau is included for patients in Cohort B2 DL4B as they do not have the sufficient samples at the necessary time points to calculate a terminal half-life so any estimation would not be reliable.
OG0016310.38(4695.62 to 14106.75)
OG002NA(NA to NA)No AUCtau is included for patients in Cohort B2 DL3A as they do not have the sufficient samples at the necessary time points to calculate a terminal half-life so any estimation would not be reliable.
OG0037594.16(7594.16 to 7594.16)
OG003
Cohort A1 DL4
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 95 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG004
Cohort A1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG005
Cohort B1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG0039
OG0046
OG0055
Title
Denominators
Categories
Title
Measurements
OG0001
OG0010
OG0020
OG0030
OG0042
OG0052
Units
Counts
Participants
OG0006
OG0016
OG0024
Title
Denominators
Categories
Title
Measurements
OG0002
OG0013
OG0022
Lorlatinib will be given orally once daily continuously for 28 days at 115mg/m2/dose. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG002
Cohort B2 DL3A
Lorlatinib will be given orally once daily continuously for 28 days at 100mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG003
Cohort B2 DL4A
Lorlatinib will be given orally once daily continuously for 28 days at 150mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
Units
Counts
Participants
OG0003
OG00112
OG0021
OG0031
Title
Denominators
Categories
Title
Measurements
OG0001
OG0015
OG0021
OG0031
OG003
Cohort A1 DL4
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 95 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG004
Cohort A1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
OG005
Cohort B1 DL5
Lorlatinib will be given orally once daily continuously for 28 days. The dose level of lorlatinib will be 115 mg/m2/dose. Patients must be under 18 years of age at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Units
Counts
Participants
OG0003
OG0013
OG0023
OG0039
OG0046
OG0051
Title
Denominators
Categories
Title
Measurements
OG000287(243 to 639)
OG001558(343 to 623)
OG002659(609 to 670)
OG0031100(590 to 1880)
OG0041280(708 to 2090)
OG0051800(1800 to 1800)
Units
Counts
Participants
OG0005
OG0016
OG0024
Title
Denominators
Categories
Title
Measurements
OG000569(341 to 1830)
OG001710(502 to 912)
OG002878.5(602 to 1100)
OG002
Cohort B2 DL3A
Lorlatinib will be given orally once daily continuously for 28 days at 100mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.
OG003
Cohort B2 DL4A
Lorlatinib will be given orally once daily continuously for 28 days at 150mg/day. Lorlatinib should be administered at least one hour prior to conventional chemotherapy (Cyclophosphamide and Topotecan) on days 1-5 of each cycle. Patients must be 18 years of age or older at time of enrollment.
Lorlatinib: Lorlatinib will be given orally once daily continuously in 28-day cycles. Lorlatinib will be provided as 5 mg or 25 mg tablets.
Cyclophosphamide: Cyclophosphamide 250mg/m2/day will be administered as a 30 minute IV infusion on days 1-5 of each cycle
Topotecan: Topotecan 0.75mg/m2/day will be administered as a 30 minute IV infusion immediately following cyclophosphamide on days 1-5 of each cycle
Filgrastim/pegfilgrastim: Filgrastim is to be given with each course beginning 24-48 hours following completion of cyclophosphamide and topotecan and continued through post-nadir count recovery with an ANC > 2000/mm^3 at 5mcg/kg/day. Filgrastim must be discontinued at least 24 hours prior to the start of the next course of therapy.
Pegfilgrastim (100mcg/kg; 6mg maximum dose) may be substituted and is given one time at 24-48 hours from completion of cyclophosphamide and topotecan.