Vincristine Sulfate Liposome Injection (Marqibo®) in Comb... | NCT02879643

Name	Class
Spectrum Pharmaceuticals, Inc	INDUSTRY

Label	Type	Description	Intervention Names
Cohort A: Marqibo and UK ALL R3 backbone	Experimental	Marqibo®: given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. Mitoxantrone: given by intravenous (IV) infusion on days 1 and 2. PEG-asparaginase: given as an injection into the muscle on says 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8.	Drug: Marqibo
Cohort B: Marqibo and lower intensity UK ALL R3 backbone	Experimental	Marqibo®: given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. PEG-asparaginase: given as an injection into the muscle on days 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8.	Drug: Marqibo
Cohort C: Marqibo and maintenance regimen	Experimental	Marqibo®: given by intravenous (IV) infusion on day 1 Dexamethasone orally twice daily on days 1-5 Methotrexate: given orally on days 1 and 8 Mercaptopurine: given orally daily on days 1-13	Drug: Marqibo

Name	Type	Description	Arm Group Labels	Other Names
Marqibo	Drug	The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.

Measure	Description	Time Frame
Number of Participants With Dose Limiting Toxicities as a Measure of Safety and Tolerability	Number of Participants with Dose Limiting Toxicities as a Measure of Safety and Tolerability at different dose levels of Marqibo. Dose Level 1 = 1.5 mg/m^2. Dose Level 2 = 2.0 mg/m^2. Cohort A and B accrued at both Dose Levels. Cohort C accrued only at Dose Level 2.	9 weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria

Age

-Patients must be ≥ 1 and ≤ 21 years of age at the time of enrollment.

Diagnosis

Cohort A: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL) or mixed phenotypic acute leukemia with ≥ 5% blasts in the bone marrow (M2 or M3), with or without extramedullary disease) or a diagnosis of lymphoblastic lymphoma.
Cohorts B & C: Patients must have a diagnosis of acute lymphoblastic leukemia (ALL), lymphoblastic lymphoma, or mixed phenotypic acute leukemia with any level of detectable disease (minimal residual disease level acceptable) with or without extramedullary disease

Performance Level -Karnofsky > 50% for patients > 16 years of age and Lansky > 50% for patients ≤ 16 years of age.

Prior Therapy

Patients must have recovered from the acute toxic effects (≤ Grade 2 or baseline) of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study, unless otherwise specified. Subjects with disease related cytopenias will be eligible.
Patients must have relapsed or refractory disease after attaining at least a first remission. They may be in first to third relapse..
Patients with Philadelphia chromosome t(9;22) positive disease must have received at least two prior tyrosine kinase inhibitors.
Patients who have experienced their relapse after a Hematopoietic stem cell transplantation (HSCT) are eligible, provided they have no evidence of graft-versus-host disease (GVHD) and are at least 100 days post-transplant at the time of enrollment.
Prior anthracycline lifetime cumulative exposure: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy.
1. Cohort A: Patients must have less than 320 mg/m2 (or 400 mg/m2 if prior cardioprotection) lifetime exposure of anthracycline chemotherapy (See Appendix 2 for anthracycline calculation worksheet).
2. Cohorts B & C: There is no limit on prior anthracycline exposure.
Hematopoietic growth factors: It must have been at least seven days since the completion of therapy with granulocyte colony-stimulating factor (GCSF) or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta®).
Biologic anti-neoplastic agents: At least seven days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond seven days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair or vice chair.
Monoclonal antibodies: At least three half-lives (or 30 days-whichever is longer) of the antibody must have elapsed after the last dose of monoclonal antibody. (e.g., Rituximab = 66 days, Epratuzumab = 69 days)
Immunotherapy: At least 30 days after the completion of any type of immunotherapy, e.g. tumor vaccines, chimeric antigen receptor T-cells.
Recent prior chemotherapy: At least 10 days after standard vincristine and the completion of any type of chemotherapy induction regimen. At least 3 weeks after radiation therapy. At least 30 days after the completion of any investigational neoplastic agent is also required. An investigational agent is defined as any drug that is not approved and licensed for sale by the FDA for institutions in the United States, by Health Canada for institutions in Canada and by The Therapeutic Goods Administration for institutions in Australia.

Exceptions:

There is no time restriction in regard to prior intrathecal chemotherapy provided there is complete recovery from any acute toxic effects of such; it is allowable to enroll a patient that has received IT Cytarabine (ARA-C), IT Methotrexate (MTX) or triple IT therapy within 14 days of enrollment as part of their evaluation to diagnose disease relapse. The IT therapy given within 14 days of initiation of protocol specified chemotherapy, may substitute for the day 1 IT in cohorts A and B
Subjects with rapidly progressive disease may receive hydroxyurea until they begin study therapy;
Patients who relapse while on maintenance-type ALL therapy or are receiving maintenance therapy for disease stabilization will not require a wash-out period before entry into this study. However, there must be at least 10 days after any dose of standard vincristine.

Renal and Hepatic Function

Renal function: Patient's serum creatinine must be ≤ 1.5 x institutional upper limit of normal (ULN) according to age. If the serum creatinine is greater than 1.5 times normal, the patient must have a calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70milliliter/min/1.73m2. Alternatively, a 24-hour creatinine clearance may also be used.
Hepatic function: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be < 5 x institutional upper limit of norm ULN. Total bilirubin must be ≤ 1.5 x ULN (except in the case of subjects with documented Gilbert's disease ≤ 5 × ULN).

Cardiac Function

-Patients must have a shortening fraction ≥ 27% or an ejection fraction ≥ 55% by echocardiogram, cardiac MRI or multigated acquisition scan (MUGA).

Reproductive Function

Female patients must not be pregnant and those of childbearing potential must have a negative urine or serum pregnancy test confirmed within one week prior to enrollment.
Female patients with infants must agree not to breastfeed their infants while on this study.
Male and female patients of childbearing potential must agree to use an effective method of contraception during the study.

Exclusion Criteria

Patients will be excluded if they have isolated testicular disease.

Patients will be excluded if they have previously received Marqibo®.

Patients will be excluded if they have a known allergy to any of the drugs used in the study, with the exception that patients with an allergy to PEG-asparaginase who can receive Erwinia asparaginase are eligible. Patients unable to receive any formulation of asparaginase may only enroll on cohort C

Patients will be excluded if they have active, uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment.

Patients who require azole antifungal agents will be excluded. Azoles must be discontinued at least one week prior to the start of Marqibo®.

Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, another investigational agent or immunotherapy during the study period.

Patients with pre-existing, persistent grade 2 or greater sensory or motor neuropathy from any cause will be excluded.

Patients will be excluded if they have, significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or adherence with the protocol treatment or procedures or interfere with consent, study participation, follow up, or interpretation of study results.Patients with Down syndrome will not be eligible for enrollment on Cohort A

Patients with a known history of human immunodeficiency virus (HIV) will will be excluded due to the increased risk of complications such as severe infection and unknown interaction of Marqibo® with antiretroviral drugs.

Active hepatitis B or C infection as defined by seropositive for hepatitis B (hepatitis B surface antigen (HBsAg)) or hepatitis C and elevated liver transaminases (defined as above the ULN per the institution normal ranges).

Facility	Status	City	State	ZIP	Country	Contacts
Childrens Hospital Los Angeles		Los Angeles	California	90027	United States
Children's Hospital Orange County

PubMed Identifier	Type	Citation	Retractions
39937083	Derived	Shah NN, Schafer ES, Chi YY, Malvar J, Heym KM, Place AE, Burns M, Chang BH, Slone T, Verma A, Gossai N, Shaw PH, Burke MJ, Hermiston M, Schore RJ, Cooper T, Pauly M, Rushing T, Jarosinski P, Florendo E, Yates B, Widemann BC, Peer CJ, Figg WD, Silverman LB, Bhojwani D, Wayne AS. Vincristine Sulfate Liposome Injection With Combination Chemotherapy for Children, Adolescents, and Young Adults With Relapsed Acute Lymphoblastic Leukemia: A Therapeutic Advances in Childhood Leukemia and Lymphoma Consortium Trial. Pediatr Blood Cancer. 2025 May;72(5):e31584. doi: 10.1002/pbc.31584. Epub 2025 Feb 12.

ID	Title	Description
FG000	Cohort A Dose Level 1: Marqibo and UK ALL R3 Backbone	Marqibo® (1.5 mg/m^2): given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. Mitoxantrone: given by intravenous (IV) infusion on days 1 and 2. PEG-asparaginase: given as an injection into the muscle on says 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8. Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.

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	Dec 8, 2021

Arm/Group Information

ID	Title	Description
BG000	Cohort A Dose Level 1: Marqibo and UK ALL R3 Backbone	Marqibo® (1.5 mg/m^2): given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. Mitoxantrone: given by intravenous (IV) infusion on days 1 and 2. PEG-asparaginase: given as an injection into the muscle on says 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8. Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.
BG001	Cohort A Dose Level 2: Marqibo and UK ALL R3 Backbone	Marqibo® (2.0 mg/m^2): given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. Mitoxantrone: given by intravenous (IV) infusion on days 1 and 2. PEG-asparaginase: given as an injection into the muscle on says 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8. Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.
BG002	Cohort B Dose Level 1: Marqibo and Lower Intensity UK ALL R3 Backbone	Marqibo® (1.5 mg/m^2): given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. PEG-asparaginase: given as an injection into the muscle on days 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8. Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.
BG003	Cohort B Dose Level 2: Marqibo and Lower Intensity UK ALL R3 Backbone	Marqibo® (2.0 mg/m^2): given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. PEG-asparaginase: given as an injection into the muscle on days 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8. Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.
BG004	Cohort C Dose Level 2: Marqibo and Maintenance Regimen	Marqibo® (2.0 mg/m^2): given by intravenous (IV) infusion on day 1 Dexamethasone orally twice daily on days 1-5 Methotrexate: given orally on days 1 and 8 Mercaptopurine: given orally daily on days 1-13 Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.
BG005	Total	Total of all reporting groups

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

Number of Participants With Dose Limiting Toxicities as a Measure of Safety and Tolerability

Number of Participants with Dose Limiting Toxicities as a Measure of Safety and Tolerability at different dose levels of Marqibo. Dose Level 1 = 1.5 mg/m^2. Dose Level 2 = 2.0 mg/m^2. Cohort A and B accrued at both Dose Levels. Cohort C accrued only at Dose Level 2.

Posted

Count of Participants

Participants

9 weeks

ID	Title	Description
OG000	Cohort A Dose Level 1: Marqibo and UK ALL R3 Backbone	Marqibo®(1.5 mg/m^2): given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. Mitoxantrone: given by intravenous (IV) infusion on days 1 and 2. PEG-asparaginase: given as an injection into the muscle on says 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8. Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.
OG001	Cohort A Dose Level 2: Marqibo and UK ALL R3 Backbone	Marqibo®(2.0 mg/m^2): given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. Mitoxantrone: given by intravenous (IV) infusion on days 1 and 2. PEG-asparaginase: given as an injection into the muscle on says 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8. Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.
OG002	Cohort B Dose Level 1: Marqibo and Lower Intensity UK ALL R3 Backbone	Marqibo®(1.5 mg/m^2): given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. PEG-asparaginase: given as an injection into the muscle on days 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8. Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.
OG003	Cohort B Dose Level 2: Marqibo and Lower Intensity UK ALL R3 Backbone	Marqibo®(2.0 mg/m^2): given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. PEG-asparaginase: given as an injection into the muscle on days 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8. Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.
OG004	Cohort C Dose Level 2: Marqibo and Maintenance Regimen	Marqibo®(2.0 mg/m^2): given by intravenous (IV) infusion on day 1 Dexamethasone orally twice daily on days 1-5 Methotrexate: given orally on days 1 and 8 Mercaptopurine: given orally daily on days 1-13 Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.

Units	Counts
Participants	OG00012 OG0014 OG0026 OG003

Title

Denominators

Categories

Title	Measurements
DLT	OG0000 OG0012 OG0020 OG003

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Cohort A Dose Level 1: Marqibo and UK ALL R3 Backbone	Marqibo®: given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. Mitoxantrone: given by intravenous (IV) infusion on days 1 and 2. PEG-asparaginase: given as an injection into the muscle on says 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8. Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.	12	7	12	12	12
EG001	Cohort A Dose Level 2: Marqibo and UK ALL R3 Backbone	Marqibo®: given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. Mitoxantrone: given by intravenous (IV) infusion on days 1 and 2. PEG-asparaginase: given as an injection into the muscle on says 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8. Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.	4	4	4	4	4
EG002	Cohort B Dose Level 1: Marqibo and Lower Intensity UK ALL R3 Backbone	Marqibo®: given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. PEG-asparaginase: given as an injection into the muscle on days 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8. Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.	6	0	6	6	6
EG003	Cohort B Dose Level 2: Marqibo and Lower Intensity UK ALL R3 Backbone	Marqibo®: given by intravenous (IV) infusion on days 1, 8, 15 and 22. Dexamethasone orally twice daily on days 1-5 and 15-19. PEG-asparaginase: given as an injection into the muscle on days 3 and 17. Methotrexate IT: given intrathecally (used to treat the brain and spinal cord and is given using a needle inserted into the spinal canal) on days 1 and 8. Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.	2	1	2	2	2
EG004	Cohort C: Marqibo and Maintenance Regimen	Marqibo®: given by intravenous (IV) infusion on day 1 Dexamethasone orally twice daily on days 1-5 Methotrexate: given orally on days 1 and 8 Mercaptopurine: given orally daily on days 1-13 Marqibo: The focus of the study design and statistical analysis is to determine whether Marqibo® can be substituted for standard vincristine and successfully administered to patients with relapsed ALL in three different treatment cohorts: (A) treatment with the UK ALL R3 regimen; (B) treatment with UK ALL R3 regimen without mitoxantrone, and (C) treatment with ALL maintenance therapy. Secondary objectives include estimating rates of serious toxicities and therapy delays in each of these cohorts.	5	5	5	5	5

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE 4.0	Non-systematic Assessment	EG00011 affected12 at risk EG0014 affected4 at risk EG0026 affected6 at risk EG0032 affected2 at risk EG0044 affected5 at risk
Disseminated intravascular coagulation	Blood and lymphatic system disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	CTCAE 4.0	Non-systematic Assessment	EG0004 affected12 at risk EG0013 affected4 at risk EG0022 affected6 at risk EG003
Cardiac disorders - Other, specify	Cardiac disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Chest pain - cardiac	Cardiac disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Sinus bradycardia	Cardiac disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Sinus tachycardia	Cardiac disorders	CTCAE 4.0	Non-systematic Assessment	EG0002 affected12 at risk EG0010 affected4 at risk EG0022 affected6 at risk EG003
Blurred vision	Eye disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Dry eye	Eye disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Eye pain	Eye disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Photophobia	Eye disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Abdominal distension	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Abdominal pain	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0004 affected12 at risk EG0011 affected4 at risk EG0022 affected6 at risk EG003
Ascites	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Constipation	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0004 affected12 at risk EG0011 affected4 at risk EG0023 affected6 at risk EG003
Diarrhea	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0004 affected12 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Dyspepsia	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Dysphagia	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Enterocolitis	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Gastrointestinal disorders - Other, specify	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Lower gastrointestinal hemorrhage	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Mucositis oral	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Nausea	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0008 affected12 at risk EG0011 affected4 at risk EG0022 affected6 at risk EG003
Oral dysesthesia	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Oral pain	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Pancreatitis	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0012 affected4 at risk EG0020 affected6 at risk EG003
Periodontal disease	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Proctitis	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Rectal pain	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Stomach pain	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Vomiting	Gastrointestinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0005 affected12 at risk EG0011 affected4 at risk EG0023 affected6 at risk EG003
Edema face	General disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Edema limbs	General disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Fatigue	General disorders	CTCAE 4.0	Non-systematic Assessment	EG0004 affected12 at risk EG0011 affected4 at risk EG0022 affected6 at risk EG003
Fever	General disorders	CTCAE 4.0	Non-systematic Assessment	EG0004 affected12 at risk EG0011 affected4 at risk EG0022 affected6 at risk EG003
General disorders and administration site conditions - Other, specify	General disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Infusion related reaction	General disorders	CTCAE 4.0	Non-systematic Assessment	EG0002 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Non-cardiac chest pain	General disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Pain	General disorders	CTCAE 4.0	Non-systematic Assessment	EG0002 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Hepatobiliary disorders - Other, specify	Hepatobiliary disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Allergic reaction	Immune system disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Cytokine release syndrome	Immune system disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Encephalitis infection	Infections and infestations	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Infections and infestations - Other, specify	Infections and infestations	CTCAE 4.0	Non-systematic Assessment	EG0003 affected12 at risk EG0013 affected4 at risk EG0021 affected6 at risk EG003
Rash pustular	Infections and infestations	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Sepsis	Infections and infestations	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Sinusitis	Infections and infestations	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Upper respiratory infection	Infections and infestations	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Fall	Injury, poisoning and procedural complications	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Activated partial thromboplastin time prolonged	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0023 affected6 at risk EG003
Alanine aminotransferase increased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0009 affected12 at risk EG0013 affected4 at risk EG0024 affected6 at risk EG003
Alkaline phosphatase increased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0004 affected12 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Aspartate aminotransferase increased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0009 affected12 at risk EG0013 affected4 at risk EG0025 affected6 at risk EG003
Blood bilirubin increased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0002 affected12 at risk EG0011 affected4 at risk EG0023 affected6 at risk EG003
Blood lactate dehydrogenase increased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Creatinine increased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Ejection fraction decreased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Electrocardiogram QT corrected interval prolonged	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Fibrinogen decreased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
GGT increased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0003 affected12 at risk EG0012 affected4 at risk EG0020 affected6 at risk EG003
INR increased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0022 affected6 at risk EG003
Lipase increased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0012 affected4 at risk EG0020 affected6 at risk EG003
Lymphocyte count decreased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0008 affected12 at risk EG0013 affected4 at risk EG0026 affected6 at risk EG003
Neutrophil count decreased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0009 affected12 at risk EG0014 affected4 at risk EG0026 affected6 at risk EG003
Platelet count decreased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG00010 affected12 at risk EG0014 affected4 at risk EG0025 affected6 at risk EG003
Serum amylase increased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Weight loss	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0002 affected12 at risk EG0010 affected4 at risk EG0022 affected6 at risk EG003
White blood cell decreased	Investigations	CTCAE 4.0	Non-systematic Assessment	EG0009 affected12 at risk EG0014 affected4 at risk EG0026 affected6 at risk EG003
Hyperphosphatemia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Anorexia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0004 affected12 at risk EG0011 affected4 at risk EG0024 affected6 at risk EG003
Dehydration	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Glucose intolerance	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Hypercalcemia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Hyperglycemia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0006 affected12 at risk EG0013 affected4 at risk EG0024 affected6 at risk EG003
Hyperkalemia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0004 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Hypermagnesemia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0005 affected12 at risk EG0012 affected4 at risk EG0022 affected6 at risk EG003
Hypernatremia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Hypertriglyceridemia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Hyperuricemia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Hypoalbuminemia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG00011 affected12 at risk EG0014 affected4 at risk EG0025 affected6 at risk EG003
Hypocalcemia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0007 affected12 at risk EG0011 affected4 at risk EG0025 affected6 at risk EG003
Hypoglycemia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0004 affected12 at risk EG0010 affected4 at risk EG0022 affected6 at risk EG003
Hypokalemia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0005 affected12 at risk EG0014 affected4 at risk EG0023 affected6 at risk EG003
Hypomagnesemia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0005 affected12 at risk EG0012 affected4 at risk EG0024 affected6 at risk EG003
Hyponatremia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG00010 affected12 at risk EG0014 affected4 at risk EG0024 affected6 at risk EG003
Hypophosphatemia	Metabolism and nutrition disorders	CTCAE 4.0	Non-systematic Assessment	EG0006 affected12 at risk EG0012 affected4 at risk EG0024 affected6 at risk EG003
Arthralgia	Musculoskeletal and connective tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected4 at risk EG0022 affected6 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0022 affected6 at risk EG003
Generalized muscle weakness	Musculoskeletal and connective tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Kyphosis	Musculoskeletal and connective tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Muscle weakness lower limb	Musculoskeletal and connective tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Muscle weakness upper limb	Musculoskeletal and connective tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0003 affected12 at risk EG0011 affected4 at risk EG0022 affected6 at risk EG003
Dizziness	Nervous system disorders	CTCAE 4.0	Non-systematic Assessment	EG0003 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Headache	Nervous system disorders	CTCAE 4.0	Non-systematic Assessment	EG0004 affected12 at risk EG0013 affected4 at risk EG0022 affected6 at risk EG003
Nervous system disorders - Other, specify	Nervous system disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Paresthesia	Nervous system disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Presyncope	Nervous system disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Somnolence	Nervous system disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Syncope	Nervous system disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Tremor	Nervous system disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0022 affected6 at risk EG003
Agitation	Psychiatric disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Anxiety	Psychiatric disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0022 affected6 at risk EG003
Confusion	Psychiatric disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Delirium	Psychiatric disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Depression	Psychiatric disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Insomnia	Psychiatric disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Acute kidney injury	Renal and urinary disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Hematuria	Renal and urinary disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Proteinuria	Renal and urinary disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Urinary frequency	Renal and urinary disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Reproductive system and breast disorders - Other, specify	Reproductive system and breast disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Vaginal discharge	Reproductive system and breast disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Vaginal dryness	Reproductive system and breast disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Atelectasis	Respiratory, thoracic and mediastinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0022 affected6 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0022 affected6 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0011 affected4 at risk EG0021 affected6 at risk EG003
Sore throat	Respiratory, thoracic and mediastinal disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0002 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0020 affected6 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0001 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0003 affected12 at risk EG0010 affected4 at risk EG0021 affected6 at risk EG003
Skin and subcutaneous tissue disorders - Other, specify	Skin and subcutaneous tissue disorders	CTCAE 4.0	Non-systematic Assessment	EG0000 affected12 at risk EG0011 affected4 at risk EG0020 affected6 at risk EG003
Hypertension	Vascular disorders	CTCAE 4.0	Non-systematic Assessment	EG0003 affected12 at risk EG0014 affected4 at risk EG0021 affected6 at risk EG003

ID	Term
D007945	Leukemia, Lymphoid
D007938	Leukemia
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D014748	Vinca Alkaloids
D046948	Secologanin Tryptamine Alkaloids
D026121	Indole Alkaloids
D000470	Alkaloids
D006571	Heterocyclic Compounds
D007211	Indoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D054836	Indolizidines
D007212	Indolizines