Cell Therapy for Metastatic Melanoma Using CD8 Enriched T... | NCT01236573 | Trialant
NCT01236573
Sponsor
National Institutes of Health Clinical Center (CC)
Status
Terminated
Last Update Posted
Nov 26, 2015Estimated
Enrollment
34Actual
Phase
Phase 1Phase 2
Conditions
Skin Cancer
Metastatic Melanoma
Interventions
Fludarabine
Cyclophosphamide
IL-12 transduced TIL
Countries
United States
Protocol Section
Identification Module
NCT ID
Results Section
Participant Flow Module
Pre-assignment Details
Annotation Section
No data available
No data is available for this block.
Document Section
No data available
No data is available for this block.
Derived Section
Miscellaneous Info Module
Version Holder
NCT01236573
Obsolete or Duplicate NCT IDs
Not provided
Organization Study
110011
Secondary IDs
ID
Type
Description
Link
11-C-0011
Brief Title
Cell Therapy for Metastatic Melanoma Using CD8 Enriched Tumor Infiltrating Lymphocytes
Official Title
Phase I/II Study of Metastatic Melanoma Using Lymphodepleting Conditioning Followed by Infusion of Tumor Infiltrating Lymphocytes Genetically Engineered to Express IL-12
Acronym
Not provided
Organization
National Institutes of Health Clinical Center (CC)NIH
Status Module
Record Verification Date
Oct 2015
Overall Recruitment Status or Expanded Access Status
Terminated
Last Known Status
Not provided
Delayed Posting
Not provided
Why Stopped
Unexpected toxicities, likely due to TIL/IL-12 & low % of durable responses.
Expanded Access Info
No
Start Date
Oct 2010
Primary Completion Date
Mar 2015Actual
Completion Date
Mar 2015Actual
First Submitted Date
Nov 5, 2010
First Submission Date that Met QC Criteria
Nov 5, 2010
First Posted Date
Nov 8, 2010Estimated
Results Waived
Not provided
Results First Submitted Date
Aug 20, 2015
Results First Submitted that Met QC Criteria
Sep 24, 2015
Results First Posted Date
Oct 26, 2015Estimated
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
Oct 26, 2015
Last Update Posted Date
Nov 26, 2015Estimated
Sponsor/Collaborators Module
Responsible Party, by Official Title
Steven Rosenberg, M.D., Principal Investigator, National Institutes of Health Clinical Center (CC)Principal Investigator
Lead Sponsor
National Institutes of Health Clinical Center (CC)NIH
Collaborators
Name
Class
National Cancer Institute (NCI)
NIH
Oversight Module
Has Data Monitoring Committee (DMC)
Yes
Is FDA Regulated Drug
Not provided
Is FDA Regulated Device
Not provided
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
Background:
- One experimental treatment for certain types of cancer is cell therapy, which involves collecting lymphocytes (white blood cells) from a tumor, growing them in the laboratory in large numbers, and then modifying the cells with a gene (interleukin-12 (IL-12)) that stimulates the immune system to attack and destroy the cancer cells. Because this treatment is experimental, researchers are interested in determining the side effects and overall effectiveness of cell therapy using white blood cells modified with IL-12 as a treatment for aggressive cancer.
Objectives:
- To determine the safety and effectiveness of cell therapy using IL-12 modified tumor white blood cells to treat metastatic melanoma.
Eligibility:
- Individuals greater than or equal to 18 years of age and less than or equal to age 66 who have been diagnosed with metastatic melanoma.
Design:
Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies.
Cells for treatment will be collected during tumor biopsy or surgery.
Prior to the start of cell therapy, participants will have imaging procedures, heart and lung function tests, and blood and urine tests, as well as leukapheresis to collect additional white blood cells.
For 5 days before the cell infusion, participants will be admitted for inpatient chemotherapy with cyclophosphamide and fludarabine to suppress the immune system in preparation for the cell therapy.
Participants will receive the modified white blood cells as an infusion 1 to 4 days after the last dose of chemotherapy. The day after the infusion, participants will receive filgrastim to stimulate blood cell growth.
Participants will remain as inpatients for at least 5 to 10 days to recover from the treatment, and will be followed regularly after the treatment to study side effects and general effectiveness.
Participants who initially respond to treatment but have a relapse may have one additional treatment using the same procedure.
Detailed Description
Background:
Interleukin-12 (IL-12) is an important immunostimulatory cytokine. We have constructed a retroviral vector that contains an inducible single chain IL-12 driven by an nuclear factor of activated T-cells (NFAT) responsive promoter which can be used to mediate transfer of this gene into anti-tumor lymphocytes. This construct enables the secretion of IL-12 following stimulation of the T cell receptor.
Transduction of the IL-12 gene into mouse anti-tumor lymphocytes results in a profound increase in the ability of these lymphocytes to mediate tumor regression following administration to tumor bearing mice. These cells have a profound advantage in inducing anti-tumor responses because very few cells are needed and there is no requirement for the concomitant administration of interleukin-2 (IL-2) as is the case for conventional cell transfer immunotherapies.
Based on these murine studies we have now constructed a similar retrovirus that contains an inducible human single chain IL-12 driven by an NFAT responsive promoter. This retrovirus can be used to transduce tumor infiltrating lymphocytes (TIL) suitable for the therapy of patients with metastatic melanoma.
Objectives:
Primary objectives:
To evaluate the safety of the administration of IL-12 engineered TIL in patients receiving a non-myeloablative conditioning regimen.
Determine if the administration of IL-12 engineered TIL to patients following a non-myeloablative but lymphoid depleting preparative regimen will result in clinical tumor regression in patients with metastatic cancer.
Secondary objective:
-Determine the in vivo survival of IL-12 gene-engineered cells.
Eligibility:
Patients who are 18 years of age or older must have:
metastatic melanoma;
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
Design:
TIL will be resected from metastatic deposits and grown in IL-2 using standard techniques.
Prior to approval of amendment A, after about 2 weeks TIL will undergo cluster of differentiation 8 (CD8) enrichment on a Miltenyi column and then undergo a rapid expansion by exposure to Muromoanb-CD3) OKT-3 an IL-2 in the presence irradiated feeder cells. Four to five days later, transduction is initiated by addition of retroviral vector supernatant containing the IL-12 gene.
With approval of amendment A, TIL will not undergo CD8 enrichment. Starting with cohort 5, after initial growth, TIL undergo a rapid expansion by exposure to OKT-3 and IL-2 in the presence irradiated feeder cells. Four to five days later, transduction is initiated by addition of retroviral vector supernatant containing the IL-12 gene.
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL. Cohorts of 3 patients each will receive increasing cell doses.
Patients will undergo complete evaluation of tumor with physical examination, computed tomography (CT) of the chest, abdomen and pelvis and clinical laboratory evaluation four to six weeks after treatment. If the patient has stable disease (SD) or tumor shrinkage, repeat complete evaluations will be performed every 1-3 months. After the first year, patients continuing to respond will continue to be followed with this evaluation every 3-4 months until off study criteria are met.
The study will be conducted using a Phase I/II optimal design. The protocol will proceed in a phase 1 dose escalation design.
Prior to approval of amendment A, the protocol enrolled 1 patient in each of the first 3 dose cohorts. Cohort 4 proceeded in a phase 1 dose escalation design, with of n=3. Should a single patient experience a dose limiting toxicity due to the cell transfer at a particular dose level, additional patients would be treated at that dose to confirm that no greater than 1/6 patients have a dose-limiting toxicity (DLT) prior to proceeding to the next higher level. If a level with 2 or more DLTs in 3-6 patients has been identified, three additional patients will be accrued at the next- lowest dose, for a total of 6, in order to further characterize the safety of the maximum tolerated dose.
With approval of amendment A, no additional patients will be enrolled in cohort 4, and the protocol will enroll 1 patient in cohort 5 with a dose of 1 X 10^7 bulk young TIL cells. Cohorts 6-12 will proceeded in a phase 1 dose escalation design, with an n=3. Should a single patient experience a dose limiting toxicity due to the cell transfer at a particular dose level, additional patients would be treated at that dose to confirm that no greater than 1/6 patients have a DLT prior to proceeding to the next higher level. If a level with 2 or more DLTs in 3-6 patients has been identified, three additional patients will be accrued at the next-lowest dose, for a total of 6, in order to further characterize the safety of the maximum tolerated dose prior to starting the pahse II portion. If a dose limiting toxicity occurs in the cohort 4, that cohort will be expanded to 6 patients. If 2 DLTs are encountered in this cohort, the study will be terminated.
Once the maximum tolerated dose (MTD) has been determined, the study then would proceed to the phase II portion using a phase II optimal design where initially 21 evaluable patients will be enrolled. If 0 or 1 of the 21 patients experiences a clinical response, then no further patients will be enrolled but if 2 or more of the first 21 evaluable patients enrolled have a clinical response, then accrual will continue until a total of 41 evaluable patients have been enrolled.
The objective will be to determine if the combination of lymphocyte depleting chemotherapy, and IL-12 gene engineered lymphocytes is associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% partial response (PR) + complete response (CR) rate (p1=0.20).
Conditions Module
Conditions
Skin Cancer
Metastatic Melanoma
Keywords
Gene Therapy
Immunotherapy
Adoptive Cell Therapy
Metastatic Melanoma
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 1Phase 2
Interventional Study Design
Allocation
Biospecimen
No data available
No data is available for this block.
Enrollment
34Actual
Arms/Interventions Module
Arm Groups
Label
Type
Description
Intervention Names
Group 1 - CD8 + TIL expressing IL-12 1x10^6
Experimental
Phase 1. Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of interleukin-12 (IL-12) gene-transduced tumor infiltrating lymphocytes (TIL).
Drug: Fludarabine
Drug: Cyclophosphamide
Biological: IL-12 transduced TIL
Group 2 - CD8 + TIL expressing IL-12 3x10^6
Experimental
Phase 1. Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Drug: Fludarabine
Drug: Cyclophosphamide
Biological: IL-12 transduced TIL
Group 3 - CD8 + TIL expressing IL-12 1x10^7
Experimental
Phase 1. Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Drug: Fludarabine
Drug: Cyclophosphamide
Biological: IL-12 transduced TIL
Group 4- CD8+TIL expressing IL-12 3x10^7
Experimental
Phase 1. Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Interventions
Name
Type
Description
Arm Group Labels
Other Names
Fludarabine
Drug
Fludarabine 25 mg/m^2/day intravenous piggyback (IVPB) daily over 30 minutes for 5 days.
Group 1 - CD8 + TIL expressing IL-12 1x10^6
Group 10- Bulk TIL expressing IL12 3x10^9
Outcomes Module
Primary Outcomes
Measure
Description
Time Frame
Maximum Tolerated Dose (MTD)
The MTD was determined by evaluating dose limiting toxicities (DLT) of participants that received increasing doses of intravenous infusion of IL-12 gene transduced tumor infiltrating lymphocytes (TIL) (i.e., 1x10^6, 3x10^6, 3x10^7, 1x10^7, 3x10^7, 1x10^8, 3x10^8, 1x10^9, and 3x10^9) in cohorts 1-10. Maximum tolerated cell dose is the highest dose at which \
4 years
Response (Complete Response (CR) + Partial Response (PR)) to Therapy
Response was determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline um LD. Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more lesions.
4 years
Secondary Outcomes
Measure
Description
Time Frame
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
49 months and 20 days
Other Outcomes
Not provided
Eligibility Module
Eligibility Criteria
INCLUSION CRITERIA:
Metastatic melanoma with evaluable disease.
Greater than or equal to 18 years of age and less than or equal to age 66.
Willing to sign a durable power of attorney
Able to understand and sign the Informed Consent Document
Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1
Life expectancy of greater than three months
Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for up to four months after the cells are no longer detected in the blood.
Serology:
Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by reverse transcription polymerase chain reaction (RT-PCR) and be hepatitis C virus ribonucleic acid (HCV RNA) negative.
Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
Hematology:
Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim.
White blood cell (WBC) (> 3000/mm^3).
Platelet count greater than 100,000/mm^3.
Hemoglobin greater than 8.0 g/dl.
Chemistry:
Serum alanine transaminase (ALT)/aspartate transaminase (AST) less or equal to 2.5 times the upper limit of normal.
Serum creatinine less than or equal to 1.6 mg/dl.
Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilberts Syndrome who must have a total bilirubin less than 3.0 mg/dl.
More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
EXCLUSION CRITERIA:
Previous treatment with interleukin-12 (IL-12).
Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.
Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities).
Concurrent systemic steroid therapy.
History of severe immediate hypersensitivity reaction to any of the agents used in this study.
In patients > 60 years old and/or history of coronary revasularization or ischemic symptoms, documented left ventricular ejection fraction (LVEF) of less than or equal to 45%.
Accepts Healthy Volunteers
No
Sex
All
Sex/Gender Based
Not provided
Sex/Gender Description
Not provided
Minimum Age
18 Years
Maximum Age
66 Years
Standard Ages
AdultOlder Adult
Study Population
Not provided
Sampling Method
Not provided
Contacts/Locations Module
Central Contacts
Not provided
Overall Officials
Name
Affiliation
Role
Steven A Rosenberg, M.D.
National Cancer Institute (NCI)
Principal Investigator
Locations
Facility
Status
City
State
ZIP
Country
Contacts
National Institutes of Health Clinical Center, 9000 Rockville Pike
Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ. Cancer statistics, 2007. CA Cancer J Clin. 2007 Jan-Feb;57(1):43-66. doi: 10.3322/canjclin.57.1.43.
Atkins MB, Lotze MT, Dutcher JP, Fisher RI, Weiss G, Margolin K, Abrams J, Sznol M, Parkinson D, Hawkins M, Paradise C, Kunkel L, Rosenberg SA. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999 Jul;17(7):2105-16. doi: 10.1200/JCO.1999.17.7.2105.
See Also Links
Not provided
Available IPD Information
Not provided
IPD Sharing Statement Module
No data available
No data is available for this block.
Not provided
Recruitment Details
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
FG000
Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
FG001
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
FG002
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
FG003
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
FG004
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
FG005
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
FG006
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
FG007
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
FG008
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
FG009
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
FG010
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
Periods
Title
Milestones
Reasons Not Completed
Phase 1-Dose Escalation-Cohorts 1-4
Type
Comment
Milestone Data
STARTED
FG0001 subjects
FG0011 subjects
FG0026 subjects
FG0031 subjects
FG004
COMPLETED
FG0001 subjects
FG0011 subjects
FG0026 subjects
FG0031 subjects
FG004
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG004
Phase 1-Dose Escalation-Cohorts 5-10
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Phase 2- MTD/Anti-IL-12 Cells-Cohort 11
Type
Comment
Milestone Data
STARTED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG003
Baseline Characteristics Module
Baseline Analysis Population Description
Not provided
Type of Units Analyzed
Not provided
Arm/Group Information
ID
Title
Description
BG000
Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
Denominators
Units
Counts
Participants
BG000
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
Outcome Measures Module
Outcome Measures
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
Maximum Tolerated Dose (MTD)
The MTD was determined by evaluating dose limiting toxicities (DLT) of participants that received increasing doses of intravenous infusion of IL-12 gene transduced tumor infiltrating lymphocytes (TIL) (i.e., 1x10^6, 3x10^6, 3x10^7, 1x10^7, 3x10^7, 1x10^8, 3x10^8, 1x10^9, and 3x10^9) in cohorts 1-10. Maximum tolerated cell dose is the highest dose at which \
Posted
Number
Cells
4 years
ID
Title
Description
OG000
All Phase I Participants
All phase I participants who received at least one dose intravenously of CD8 + TIL expressing IL-12 in Groups 1-4, and Bulk TIL expressing IL-12 in Groups 5-10 (i.e., CD8 + TIL expressing IL-12 1x10^6, CD8 + TIL expressing IL-12 3x10^6, CD8 + TIL expressing IL-12 3x10^7, CD8 + TIL expressing IL-12 3x10^7, Bulk TIL expressing IL-12 1x10^7, Bulk TIL expressing IL-12 3x10^7, Bulk TIL expressing IL-12 1x10^8, Bulk TIL expressing IL-12 3x10^8, Bulk TIL expressing IL-12 1x10^9, and Bulk TIL expressing IL-12 3x10^9) respectively.
Adverse Events Module
Frequency Threshold
0
Time Frame
Not provided
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
Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
Serious Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
Platelets
Blood and lymphatic system disorders
CTCAE (3.0)
Systematic Assessment
Other Adverse Events
Term
Organ System
Source Vocabulary
Assessment Type
Notes
Statistical Information
PTT (Partial Thromboplastin TIme)
Blood and lymphatic system disorders
CTCAE (3.0)
Systematic Assessment
More Info Module
Limitations and Caveats
Due to the unexpected toxicities, likely attributable to the tumor infiltrating lymphocytes (TIL) transduced with IL-12, and low percentage of durable responses, we decided to close this study.
Certain Agreements
Are all PI(s) employees of the sponsor?
No
Point of Contact
Title
Organization
Phone
Extension
Email
Dr. Steven Rosenberg
National Cancer Institute
301-496-4164
sar@mail.nih.gov
Jul 10, 2026
Removed Countries
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Submission Tracking
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Condition Browse Module
MeSH Terms
ID
Term
D012878
Skin Neoplasms
D008545
Melanoma
Ancestor Terms
ID
Term
D009371
Neoplasms by Site
D009369
Neoplasms
D012871
Skin Diseases
D017437
Skin and Connective Tissue Diseases
Browse Leaves
Not provided
Browse Branches
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Intervention Browse Module
MeSH Terms
ID
Term
C024352
fludarabine
D003520
Cyclophosphamide
Ancestor Terms
ID
Term
D010752
Phosphoramide Mustards
D009588
Nitrogen Mustard Compounds
D009150
Mustard Compounds
D006846
Hydrocarbons, Halogenated
Browse Leaves
Not provided
Browse Branches
Not provided
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
Drug: Fludarabine
Drug: Cyclophosphamide
Biological: IL-12 transduced TIL
Group 5 - Bulk TIL expressing IL-12 1x10^7
Experimental
Phase 1. Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Drug: Fludarabine
Drug: Cyclophosphamide
Biological: IL-12 transduced TIL
Group 6 - Bulk TIL expressing IL-12 3x10^7
Experimental
Phase 1. Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Drug: Fludarabine
Drug: Cyclophosphamide
Biological: IL-12 transduced TIL
Group 7- Bulk TIL expressing IL-12 1x10^8
Experimental
Phase 1. Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Drug: Fludarabine
Drug: Cyclophosphamide
Biological: IL-12 transduced TIL
Group 8 - Bulk TIL expressing IL-12 3x10^8
Experimental
Phase 1. Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Drug: Fludarabine
Drug: Cyclophosphamide
Biological: IL-12 transduced TIL
Group 9 - Bulk TIL expressing IL-12 1x10^9
Experimental
Phase 1. Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Drug: Fludarabine
Drug: Cyclophosphamide
Biological: IL-12 transduced TIL
Group 10- Bulk TIL expressing IL12 3x10^9
Experimental
Phase 1. Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Drug: Fludarabine
Drug: Cyclophosphamide
Biological: IL-12 transduced TIL
Group 11 - Bulk TIL expressing MTD 1x10^9 (Phase 2)
Experimental
Maximum tolerated dose (MTD). Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Drug: Fludarabine
Drug: Cyclophosphamide
Biological: IL-12 transduced TIL
Group 11 - Bulk TIL expressing MTD 1x10^9 (Phase 2)
Group 2 - CD8 + TIL expressing IL-12 3x10^6
Group 3 - CD8 + TIL expressing IL-12 1x10^7
Group 4- CD8+TIL expressing IL-12 3x10^7
Group 5 - Bulk TIL expressing IL-12 1x10^7
Group 6 - Bulk TIL expressing IL-12 3x10^7
Group 7- Bulk TIL expressing IL-12 1x10^8
Group 8 - Bulk TIL expressing IL-12 3x10^8
Group 9 - Bulk TIL expressing IL-12 1x10^9
Cyclophosphamide
Drug
Cyclophosphamide 60 mg/kg/day X 2 days intravenous (IV) in 250 ml dextrose 5% in water (D5W) over 1 hr.
Group 1 - CD8 + TIL expressing IL-12 1x10^6
Group 10- Bulk TIL expressing IL12 3x10^9
Group 11 - Bulk TIL expressing MTD 1x10^9 (Phase 2)
Group 2 - CD8 + TIL expressing IL-12 3x10^6
Group 3 - CD8 + TIL expressing IL-12 1x10^7
Group 4- CD8+TIL expressing IL-12 3x10^7
Group 5 - Bulk TIL expressing IL-12 1x10^7
Group 6 - Bulk TIL expressing IL-12 3x10^7
Group 7- Bulk TIL expressing IL-12 1x10^8
Group 8 - Bulk TIL expressing IL-12 3x10^8
Group 9 - Bulk TIL expressing IL-12 1x10^9
IL-12 transduced TIL
Biological
On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
Group 1 - CD8 + TIL expressing IL-12 1x10^6
Group 10- Bulk TIL expressing IL12 3x10^9
Group 11 - Bulk TIL expressing MTD 1x10^9 (Phase 2)
Kerkar SP, Goldszmid RS, Muranski P, Chinnasamy D, Yu Z, Reger RN, Leonardi AJ, Morgan RA, Wang E, Marincola FM, Trinchieri G, Rosenberg SA, Restifo NP. IL-12 triggers a programmatic change in dysfunctional myeloid-derived cells within mouse tumors. J Clin Invest. 2011 Dec;121(12):4746-57. doi: 10.1172/JCI58814. Epub 2011 Nov 7.
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COMPLETED
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NOT COMPLETED
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Type
Comment
Reasons
Death during treatment
FG0000 subjects
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FG0040 subjects
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FG0061 subjects
FG0070 subjects
FG0081 subjects
FG0091 subjects
FG0100 subjects
Not treated
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FG0030 subjects
FG004
0 subjects
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FG0050 subjects
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FG0070 subjects
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FG0090 subjects
FG0106 subjects
COMPLETED
FG0000 subjects
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FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
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FG0090 subjects
FG0105 subjects
NOT COMPLETED
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0101 subjects
Type
Comment
Reasons
Did not receive cells
FG0000 subjects
FG0010 subjects
FG0020 subjects
FG0030 subjects
FG0040 subjects
FG0050 subjects
FG0060 subjects
FG0070 subjects
FG0080 subjects
FG0090 subjects
FG0101 subjects
BG001
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
BG002
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
BG003
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
BG004
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
BG005
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
BG006
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
BG007
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
BG008
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
BG009
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
BG010
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
BG011
Total
Total of all reporting groups
1
BG0011
BG0026
BG0031
BG0041
BG0054
BG0063
BG0073
BG0084
BG0094
BG0106
BG01134
Participants
Title
Denominators
Categories
Title
Measurements
<=18 years
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
BG0080
BG0090
BG0100
BG0110
Between 18 and 65 years
BG0001
BG0011
BG0026
BG0031
BG004
>=65 years
BG0000
BG0010
BG0020
BG0030
BG004
Age, Continuous
Mean
Standard Deviation
years
Title
Denominators
Categories
Title
Measurements
BG00056.0± 0
BG00150.0± 0
BG00239.0± 11.5
BG00348.0± 0
BG00460.0± 0
BG00557.3± 10.9
BG00649.0± 14.5
BG00756.0± 9.6
BG00853.5± 16.2
BG00955.8± 12.2
BG01049.3± 16.5
BG01150.7± 13.0
Sex: Female, Male
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Female
BG0001
BG0010
BG0021
BG0030
BG0040
BG0051
BG0062
BG0071
BG0081
BG0092
BG0100
BG0119
Male
BG0000
BG0011
BG0025
BG0031
BG004
Ethnicity (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
Hispanic or Latino
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0071
BG0080
BG0091
BG0100
BG0112
Not Hispanic or Latino
BG0001
BG0011
BG0026
BG0031
BG004
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
BG004
Race (NIH/OMB)
Count of Participants
Participants
Title
Denominators
Categories
Title
Measurements
American Indian or Alaska Native
BG0000
BG0010
BG0020
BG0030
BG0040
BG0050
BG0060
BG0070
BG0080
BG0090
BG0100
BG0110
Asian
BG0000
BG0010
BG0020
BG0030
BG004
Native Hawaiian or Other Pacific Islander
BG0000
BG0010
BG0020
BG0030
BG004
Black or African American
BG0000
BG0010
BG0020
BG0030
BG004
White
BG0001
BG0011
BG0026
BG0031
BG004
More than one race
BG0000
BG0010
BG0020
BG0030
BG004
Unknown or Not Reported
BG0000
BG0010
BG0020
BG0030
BG004
Region of Enrollment
Number
participants
Title
Denominators
Categories
United States
Title
Measurements
BG0001
BG0011
BG0026
BG0031
BG0041
BG0054
BG0063
BG0073
BG0084
BG0094
BG0106
BG01134
Units
Counts
Participants
OG00028
Title
Denominators
Categories
Title
Measurements
OG0001,000,000,000
Secondary
Number of Participants With Adverse Events
Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse event module.
Posted
Number
participants
49 months and 20 days
ID
Title
Description
OG000
Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG001
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG002
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG003
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG004
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG005
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG006
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG007
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG008
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG009
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG010
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
Units
Counts
Participants
OG0001
OG0011
OG0026
OG003
Title
Denominators
Categories
Title
Measurements
OG0001
OG0011
OG0026
OG003
Primary
Response (Complete Response (CR) + Partial Response (PR)) to Therapy
Response was determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.0. Complete response (CR) is disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline um LD. Progressive disease (PD) is at least a 20% increase in the sum of LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more lesions.
Posted
Number
participants
4 years
ID
Title
Description
OG000
Group 1 - CD8 + TIL Expressing IL-12 1x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG001
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG002
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG003
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG004
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG005
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG006
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG007
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG008
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG009
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
OG010
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
Units
Counts
Participants
OG0001
OG0011
OG0026
OG003
Title
Denominators
Categories
Complete Response (CR)
Title
Measurements
OG0000
OG0010
OG0020
OG003
0
1
1
1
EG001
Group 2 - CD8 + TIL Expressing IL-12 3x10^6 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
0
1
1
1
EG002
Group 3 - CD8 + TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
2
6
6
6
EG003
Group 4 - CD8 + TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
0
1
1
1
EG004
Group 5 - Bulk TIL Expressing IL-12 1x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
0
1
1
1
EG005
Group 6 - Bulk TIL Expressing IL-12 3x10^7 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
0
4
4
4
EG006
Group 7- Bulk TIL Expressing IL-12 1x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
1
3
3
3
EG007
Group 8 - Bulk TIL Expressing IL-12 3x10^8 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
1
3
3
3
EG008
Group 9 - Bulk TIL Expressing IL-12 1x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
1
4
4
4
EG009
Group 10 - Bulk TIL Expressing IL12 3x10^9 (Phase 1)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
1
4
4
4
EG010
Group 11 - Bulk TIL Expressing MTD 1x10^9 (Phase 2)
Patients will receive a nonmyeloablative but lymphocyte depleting preparative regimen consisting of cyclophosphamide and fludarabine followed by intravenous infusion of IL-12 gene-transduced TIL.
Fludarabine: Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Cyclophosphamide: Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W over 1 hr.
IL-12 transduced TIL: On day 0 (one to four days after the last dose of fludarabine), cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.
2
6
6
6
EG0000 events0 affected1 at risk
EG0010 events0 affected1 at risk
EG0021 events1 affected6 at risk
EG0030 events0 affected1 at risk
EG0040 events0 affected1 at risk
EG0050 events0 affected4 at risk
EG0061 events1 affected3 at risk
EG0070 events0 affected3 at risk
EG0080 events0 affected4 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected6 at risk
Fever (in the absence of neutropenia, where neutropenia is defined as ANC <1.0x10e9/L)
General disorders
CTCAE (3.0)
Systematic Assessment
EG0000 events0 affected1 at risk
EG0010 events0 affected1 at risk
EG0021 events1 affected6 at risk
EG0030 events0 affected1 at risk
EG0040 events0 affected1 at risk
EG0050 events0 affected4 at risk
EG0060 events0 affected3 at risk
EG0070 events0 affected3 at risk
EG0080 events0 affected4 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected6 at risk
Hemoglobin
Blood and lymphatic system disorders
CTCAE (3.0)
Systematic Assessment
EG0000 events0 affected1 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected1 at risk
EG0040 events0 affected1 at risk
EG0050 events0 affected4 at risk
EG0061 events1 affected3 at risk
EG0070 events0 affected3 at risk
EG0080 events0 affected4 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected6 at risk
Thrombosis/thrombus/embolism
Vascular disorders
CTCAE (3.0)
Systematic Assessment
EG0000 events0 affected1 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected1 at risk
EG0040 events0 affected1 at risk
EG0050 events0 affected4 at risk
EG0060 events0 affected3 at risk
EG0071 events1 affected3 at risk
EG0080 events0 affected4 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected6 at risk
Bilirubin (Hyperbilirubinemia)
Metabolism and nutrition disorders
CTCAE (3.0)
Systematic Assessment
EG0000 events0 affected1 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected1 at risk
EG0040 events0 affected1 at risk
EG0050 events0 affected4 at risk
EG0060 events0 affected3 at risk
EG0070 events0 affected3 at risk
EG0081 events1 affected4 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected6 at risk
Creatinine
Metabolism and nutrition disorders
CTCAE (3.0)
Systematic Assessment
EG0000 events0 affected1 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected1 at risk
EG0040 events0 affected1 at risk
EG0050 events0 affected4 at risk
EG0060 events0 affected3 at risk
EG0070 events0 affected3 at risk
EG0081 events1 affected4 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected6 at risk
Hypoxia
Respiratory, thoracic and mediastinal disorders
CTCAE (3.0)
Systematic Assessment
EG0000 events0 affected1 at risk
EG0010 events0 affected1 at risk
EG0020 events0 affected6 at risk
EG0030 events0 affected1 at risk
EG0040 events0 affected1 at risk
EG0050 events0 affected4 at risk
EG0060 events0 affected3 at risk
EG0070 events0 affected3 at risk
EG0081 events1 affected4 at risk
EG0090 events0 affected4 at risk
EG0100 events0 affected6 at risk
Thrombotic microangiopathy
Vascular disorders
CTCAE (3.0)
Systematic Assessment
(e.g., thrombotic thrombocytopenic purpura (TTP) or hemolytic uremic syndrome (HUS)