Clofarabine and Cytarabine in Treating Young Patients Wit... | NCT00372619

ID	Type	Description
CDR0000494654	Other Identifier	Clinical Trials.gov
NCI-2009-00319	Other Identifier	NCI Trial Identifier
COG-AAML0523	Other Identifier	Children's Oncology Group

Status Module

Name	Class
National Cancer Institute (NCI)	NIH

Description Module

Detailed Description

OBJECTIVES:

Primary

To define the overall response rate (complete remission or remission without platelet recovery) in young patients with relapsed or refractory acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) treated with clofarabine in combination with cytarabine.

Secondary

To determine the safety profile and tolerability of clofarabine when given in combination with cytarabine in patients with and without prior stem cell transplantation.
To identify apoptosis specific genes that are important in mediating response to clofarabine and cytarabine.
To quantitate the level of human equilibrative nucleoside transporter proteins (hENT1 and hENT2) and human concentrative nucleoside transporter proteins (hCNT2 and hCNT3) in blasts of these patients.
To determine gene expression profiles at study entry and at time of relapse in order to isolate profiles that may predict response and also to complement apoptosis specific protein arrays.
To perform serial measurements of minimal residual disease (MRD) to provide an objective determination of the effectiveness of this treatment regimen and to correlate with post remission events (relapse, death).
To perform FLT3/ITD analysis to help determine the prevalence and clinical significance of this somatic mutation in patients with relapsed AML.

OUTLINE: This is a multicenter, phase I, dose-escalation study of clofarabine followed by a phase II study. Patients are stratified according to disease (acute lymphoblastic leukemia [ALL] vs acute myeloid leukemia [AML]). (Phase I closed to accrual as of 09/16/09)

Intrathecal CNS prophylaxis (all patients with ALL and at physician's discretion for patients with AML or acute leukemia of ambiguous lineage): Patients receive intrathecal (IT) cytarabine on day 0 of the first course of induction therapy. Patients also receive IT methotrexate on day 1 of the second course of induction therapy and on day 1 of all courses of maintenance therapy.
Induction therapy:
- Course 1: Patients receive cytarabine IV over 2 hours and clofarabine IV over 2 hours on days 1-5. Patients with ≥ 5% blasts (i.e., M2 or M3 bone marrow) at days 14-21 proceed immediately to course 2 of induction therapy. Patients with < 5% blasts (i.e., M1 bone marrow) may proceed to course 2 of induction therapy at blood count recovery or at day 42.
- Course 2: Patients receive clofarabine IV over 2 hours followed by cytarabine IV over 2 hours on days 1-5. After the second course of induction therapy, patients with M2 or M3 bone marrow at days 14-21 are removed from the study. Patients with M1 bone marrow proceed to maintenance therapy 14-42 days after the initiation of course 2.
Maintenance therapy: Patients receive clofarabine and cytarabine as in induction therapy. Treatment repeats every 14-42 days for up to 10 courses in the absence of disease progression or unacceptable toxicity.

Patients may undergo blood and bone marrow sample collection periodically for correlative laboratory studies.

After completion of study therapy, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 87 patients will be accrued for this study.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Clofarabine 40 mg/m² to assess feasibility in ALL patients.	Experimental	Clofarabine 40 mg/m² to assess feasibility in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5.	Drug: clofarabine Drug: cytarabine Drug: methotrexate Other: laboratory biomarker analysis
Clofarabine 40 mg/m² to assess feasibility in AML patients.	Experimental	Clofarabine 40 mg/m² to assess feasibility in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5.	Drug: clofarabine Drug: cytarabine Drug: methotrexate Other: laboratory biomarker analysis
Clofarabine 52 mg/m² to assess feasibility in ALL patients.	Experimental

Interventions

Name	Type	Description	Arm Group Labels	Other Names
clofarabine	Drug	Given IV for 5 days	Clofarabine 40 mg/m² to assess feasibility in ALL patients. Clofarabine 40 mg/m² to assess feasibility in AML patients.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Overall Response (CR for ALL Patients), (CR + CRp for AML Patients)	Overall response for ALL patients: CR - complete remission (attainment of an M1 bone marrow (< 5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (absolute neutrophil count (ANC) > 750/μL and platelet count > 75,000/μL). Overall response for AML patients: (CR + CRp), defined as: CR - complete remission (attainment of an M1 bone marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral blood counts (absolute neutrophil count (ANC) > 1000/uL and platelet count > 100,000/uL)) or CRp - remission without platelet recovery (Attainment of an M1 bone marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of absolute neutrophil count (ANC) > 1000/uL and platelet transfusion independence (defined as: no platelet transfusions x 1 week)).	2 cycles or up to 84 days

Secondary Outcomes

Measure	Description	Time Frame
Safety and Tolerability as Measured by CTCAE v3.0	Number of participants with at least one grade 3 or higher adverse event during therapy.	End of therapy
Correlate the Expression of Apoptosis Specific Genes

Eligibility Module

Eligibility Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed diagnosis of 1 of the following:
- Acute myeloid leukemia (AML) with ≥ 5% blasts in the bone marrow (M2/M3 bone marrow) with or without extramedullary disease
- Acute lymphoblastic leukemia (ALL) with > 25% blasts in the bone marrow (M3 bone marrow) with or without extramedullary disease
- Acute leukemia of ambiguous lineage with ≥ 5% blasts in the bone marrow (M2/M3 bone marrow) with or without extramedullary disease
Disease must have relapsed after or be refractory to prior induction therapy
- Patients with AML or acute leukemia of ambiguous lineage must be in first relapse OR refractory to first induction therapy with ≤ 1 attempt at remission induction
  - Patients with AML who enroll on the phase I portion of the study must have received prior mitoxantrone hydrochloride and cytarabine for newly diagnosed AML (phase I closed to accrual as of 09/16/09)
- Patients with ALL must be in second or third relapse (≤ 3 prior induction regimens) OR refractory to reinduction in first relapse
  - Patients with ALL refractory to first induction therapy are not eligible
No acute promyelocytic leukemia
No CNS 3 involvement (i.e., WBC ≥ 5/μL in the cerebrospinal fluid with blasts present on cytospin)

PATIENT CHARACTERISTICS:

Karnofsky performance status (PS) 50-100% (> 16 years of age) OR Lansky PS 50-100% (≤ 16 years of age) OR ECOG PS 0-2
Life expectancy ≥ 8 weeks
Creatinine clearance or radioisotope glomerular filtration rate ≥ 70 mL/min
Direct bilirubin ≤ 1.5 times upper limit of normal (ULN)
ALT < 2.5 times ULN (unless it is related to leukemic involvement)
Shortening fraction ≥ 27% by echocardiogram OR ejection fraction ≥ 45% by gated radionuclide study
No evidence of dyspnea at rest or exercise intolerance
Pulse oximetry > 94% at room air
Amylase ≤ 1.5 times ULN
Lipase < 1.5 times ULN
No active, uncontrolled grade 3 or 4 infection
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
No known hepatitis B or C infection or history of cirrhosis

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from all prior therapy*
At least 14 days since prior cytotoxic therapy (except hydroxyurea and intrathecal chemotherapy)*
At least 7 days since prior biologic agent*
At least 14 days since prior monoclonal antibody therapy*
No more than 1 prior autologous or allogeneic hematopoietic stem cell transplantation
- No evidence of active graft-vs-host disease
- At least 4 months since transplantation
No other concurrent chemotherapy or immunomodulating agents
No other concurrent investigational therapy NOTE: *Patients who relapse during ALL maintenance therapy do not require a waiting period.

Name	Affiliation	Role
Bassem I. Razzouk, MD	St. Vincent Indianapolis Hospital	Study Chair
Todd Cooper, DO	University of Alabama at Birmingham	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
UAB Comprehensive Cancer Center		Birmingham	Alabama	35294	United States
Southern California Permanente Medical Group

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Clofarabine 40 mg/m² to Assess Feasibility in ALL Patients.	Clofarabine 40 mg/m² to assess feasibility in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Arm/Group Information

ID	Title	Description
BG000	Clofarabine 40 mg/m² to Assess Feasibility in ALL Patients.	Clofarabine 40 mg/m² to assess feasibility in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
BG001	Clofarabine 40 mg/m² to Assess Feasibility in AML Patients.	Clofarabine 40 mg/m² to assess feasibility in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
BG002	Clofarabine 52 mg/m² to Assess Feasibility in ALL Patients.	Clofarabine 52 mg/m² to assess feasibility in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
BG003	Clofarabine 52 mg/m² to Assess Efficacy in ALL Patients.	Clofarabine 52 mg/m² to assess efficacy in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
BG004	Clofarabine 52 mg/m² to Assess Feasibility in AML Patients.	Clofarabine 52 mg/m² to assess feasibility in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
BG005	Clofarabine 52 mg/m² to Assess Efficacy in AML Patients	Clofarabine 52 mg/m² to assess efficacy in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
BG006	Clofarabine 52 mg/m² to Assess Efficacy - Ambiguous Lineage pt	Clofarabine 52 mg/m² to assess efficacy in acute leukemia of ambiguous lineage patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
BG007	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0007 BG0011 BG0023 BG003

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00012.75± 6.37 BG00115.09± 6.33 BG002

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0005 BG0010 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0001 BG0010 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0011 BG002

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG0007 BG0011 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Overall Response (CR for ALL Patients), (CR + CRp for AML Patients)

Overall response for ALL patients: CR - complete remission (attainment of an M1 bone marrow (< 5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral counts (absolute neutrophil count (ANC) > 750/μL and platelet count > 75,000/μL).

Overall response for AML patients: (CR + CRp), defined as:

CR - complete remission (attainment of an M1 bone marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of peripheral blood counts (absolute neutrophil count (ANC) > 1000/uL and platelet count > 100,000/uL)) or CRp - remission without platelet recovery (Attainment of an M1 bone marrow (<5% blasts) with no evidence of circulating blasts or extramedullary disease and with recovery of absolute neutrophil count (ANC) > 1000/uL and platelet transfusion independence (defined as: no platelet transfusions x 1 week)).

Posted

Number

participants

2 cycles or up to 84 days

ID	Title	Description
OG000	Clofarabine 40 mg/m² to Assess Feasibility in ALL Patients.	Clofarabine 40 mg/m² to assess feasibility in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
OG001	Clofarabine 40 mg/m² to Assess Feasibility in AML Patients.	Clofarabine 40 mg/m² to assess feasibility in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
OG002	Clofarabine 52 mg/m² to Assess Feasibility in ALL Patients.	Clofarabine 52 mg/m² to assess feasibility in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
OG003	Clofarabine 52 mg/m² to Assess Efficacy in ALL Patients.	Clofarabine 52 mg/m² to assess efficacy in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
OG004	Clofarabine 52 mg/m² to Assess Feasibility in AML Patients.	Clofarabine 52 mg/m² to assess feasibility in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
OG005	Clofarabine 52 mg/m² to Assess Efficacy in AML Patients	Clofarabine 52 mg/m² to assess efficacy in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
OG006	Clofarabine 52 mg/m² to Assess Efficacy - Ambiguous Lineage pt	Clofarabine 52 mg/m² to assess efficacy in acute leukemia of ambiguous lineage patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis

Units	Counts
Participants	OG0008 OG0012 OG0023 OG003

Title

Denominators

Categories

Title	Measurements
	OG0001 OG0012 OG0020 OG003

Secondary

Safety and Tolerability as Measured by CTCAE v3.0

Number of participants with at least one grade 3 or higher adverse event during therapy.

Ineligible (n=2) and inevaluable (n=1) patients are excluded

Posted

Number

number participants

End of therapy

ID	Title	Description
OG000	Clofarabine 40 mg/m² to Assess Feasibility in ALL Patients.	Clofarabine 40 mg/m² to assess feasibility in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
OG001	Clofarabine 40 mg/m² to Assess Feasibility in AML Patients.	Clofarabine 40 mg/m² to assess feasibility in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis

Secondary

Correlate the Expression of Apoptosis Specific Genes

Correlate the expression of apoptosis specific genes with chemoresistance and determine whether therapy with clofarabine is able to overcome blocks in apoptosis through modulation of gene expression. Gene expression analysis will be performed on specimens obtained during therapy. Apoptosis specific microarray data will be analyzed using GeneTraffic software (Iobion Informatics, La Jolla CA).

The analysis was not completed, because the tissue microarray was unsuccessful.

Posted

End of therapy

ID	Title	Description
OG000	Clofarabine 40 mg/m² to Assess Feasibility in ALL Patients.	Clofarabine 40 mg/m² to assess feasibility in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis
OG001	Clofarabine 40 mg/m² to Assess Feasibility in AML Patients.

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Clofarabine 40 mg/m² to Assess Feasibility in ALL Patients.	Clofarabine 40 mg/m² to assess feasibility in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis	5	8	8	8
EG001	Clofarabine 40 mg/m² to Assess Feasibility in AML Patients.	Clofarabine 40 mg/m² to assess feasibility in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 40 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 40 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis	2	2	2	2
EG002	Clofarabine 52 mg/m² to Assess Feasibility in ALL Patients.	Clofarabine 52 mg/m² to assess feasibility in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis	2	3	3	3
EG003	Clofarabine 52 mg/m² to Assess Efficacy in ALL Patients.	Clofarabine 52 mg/m² to assess efficacy in ALL patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis	7	10	10	10
EG004	Clofarabine 52 mg/m² to Assess Feasibility in AML Patients.	Clofarabine 52 mg/m² to assess feasibility in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis	3	7	7	7
EG005	Clofarabine 52 mg/m² to Assess Efficacy in AML Patients	Clofarabine 52 mg/m² to assess efficacy in AML patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis	14	40	38	40
EG006	Clofarabine 52 mg/m² to Assess Efficacy - Ambiguous Lineage pt	Clofarabine 52 mg/m² to assess efficacy in acute leukemia of ambiguous lineage patients. Patients receive Cycle 1 (14-42 days) Cytarabine IT (aged based dosage 1-1.99 30 mg, 2-2.99 50 mg, ≥ 3 years 70 mg on Day 0, Clofarabine IV (dosage 52 mg/m2/dose) on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Cycle 2 (14-42 days) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. Maintenance cycles 1-10 (14-42 days each) Methotrexate IT (age based dosage 1-1.99 8 mg, 2-2.99 10 mg, ≥ 3 12 mg) on day 1, Clofarabine IV 52 mg/m2/dose on days 1-5, and High Dose Cytarabine IV 1000 mg/m2/dose on days 1-5. clofarabine: Given IV for 5 days cytarabine: Given IV methotrexate: Given intrathecally or IT age based dosage laboratory biomarker analysis	2	2	2	2

Serious Adverse Events

Term	Organ System	Statistical Information
Abdominal pain	Gastrointestinal disorders	EG0002 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG0030 affected10 at risk EG0040 affected7 at risk EG0050 affected40 at risk EG0060 affected2 at risk
Alanine aminotransferase increased	Investigations	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Anorexia	Metabolism and nutrition disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Aspartate aminotransferase increased	Investigations	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Bladder infection	Infections and infestations	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Blood bilirubin increased	Investigations	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Capillary leak syndrome	Vascular disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Chest wall pain	Musculoskeletal and connective tissue disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Chills	General disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Colitis	Gastrointestinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Diarrhea	Gastrointestinal disorders	EG0002 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Dyspnea	Respiratory, thoracic and mediastinal disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Fatigue	General disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	EG0002 affected8 at risk EG0011 affected2 at risk EG0020 affected3 at risk EG003
Fibrinogen decreased	Investigations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
GGT increased	Investigations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Headache	Nervous system disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypercalcemia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hyperglycemia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypermagnesemia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0011 affected2 at risk EG0020 affected3 at risk EG003
Hypertension	Vascular disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypoalbuminemia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypokalemia	Metabolism and nutrition disorders	EG0002 affected8 at risk EG0011 affected2 at risk EG0020 affected3 at risk EG003
Hyponatremia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypophosphatemia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Hypotension	Vascular disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	EG0002 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Ileus	Gastrointestinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Infections and infestations - Other	Infections and infestations	EG0004 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Left ventricular systolic dysfunction	Cardiac disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Lipase increased	Investigations	EG0001 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Nausea	Gastrointestinal disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Neuralgia	Nervous system disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Non-cardiac chest pain	General disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Pancreatitis	Gastrointestinal disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Peripheral motor neuropathy	Nervous system disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	EG0002 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Proteinuria	Renal and urinary disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Right ventricular dysfunction	Cardiac disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Sepsis	Infections and infestations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Serum amylase increased	Investigations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Sinus tachycardia	Cardiac disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Small intestinal mucositis	Gastrointestinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Tumor lysis syndrome	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Vomiting	Gastrointestinal disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003

Other Adverse Events

Term	Organ System	Statistical Information
Abdominal distension	Gastrointestinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG0031 affected10 at risk EG0041 affected7 at risk EG0050 affected40 at risk EG0060 affected2 at risk
Abdominal pain	Gastrointestinal disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Acidosis	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Acute kidney injury	Renal and urinary disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Alanine aminotransferase increased	Investigations	EG0004 affected8 at risk EG0012 affected2 at risk EG0021 affected3 at risk EG003
Alkaline phosphatase increased	Investigations	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Allergic reaction	Immune system disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Alopecia	Skin and subcutaneous tissue disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Anaphylaxis	Immune system disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Anemia	Blood and lymphatic system disorders	EG0002 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Anorexia	Metabolism and nutrition disorders	EG0001 affected8 at risk EG0011 affected2 at risk EG0020 affected3 at risk EG003
Anxiety	Psychiatric disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Aspartate aminotransferase increased	Investigations	EG0002 affected8 at risk EG0010 affected2 at risk EG0022 affected3 at risk EG003
Atelectasis	Respiratory, thoracic and mediastinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Avascular necrosis	Musculoskeletal and connective tissue disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Bladder spasm	Renal and urinary disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Blood and lymphatic system disorders - Other	Blood and lymphatic system disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Blood bilirubin increased	Investigations	EG0002 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Bone pain	Musculoskeletal and connective tissue disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Bronchospasm	Respiratory, thoracic and mediastinal disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Capillary leak syndrome	Vascular disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Cardiac disorders - Other	Cardiac disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Catheter related infection	Infections and infestations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Cheilitis	Gastrointestinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Chills	General disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Conjunctivitis	Eye disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Constipation	Gastrointestinal disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Creatinine increased	Investigations	EG0000 affected8 at risk EG0011 affected2 at risk EG0021 affected3 at risk EG003
Cushingoid	Endocrine disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Cystitis noninfective	Renal and urinary disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Dehydration	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Depressed level of consciousness	Nervous system disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Diarrhea	Gastrointestinal disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Dizziness	Nervous system disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Dry eye	Eye disorders	EG0000 affected8 at risk EG0011 affected2 at risk EG0020 affected3 at risk EG003
Dry skin	Skin and subcutaneous tissue disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Dysphagia	Gastrointestinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Dyspnea	Respiratory, thoracic and mediastinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Edema face	General disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Edema limbs	General disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Electrocardiogram QT corrected interval prolonged	Investigations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Esophagitis	Gastrointestinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Eye disorders - Other	Eye disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Eye pain	Eye disorders	EG0000 affected8 at risk EG0011 affected2 at risk EG0020 affected3 at risk EG003
Fatigue	General disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Febrile neutropenia	Blood and lymphatic system disorders	EG0003 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Fever	General disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Gastritis	Gastrointestinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
GGT increased	Investigations	EG0000 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Gum infection	Infections and infestations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Headache	Nervous system disorders	EG0002 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hematuria	Renal and urinary disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hepatic infection	Infections and infestations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hepatobiliary disorders - Other	Hepatobiliary disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypercalcemia	Metabolism and nutrition disorders	EG0004 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Hyperglycemia	Metabolism and nutrition disorders	EG0002 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Hyperkalemia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Hypermagnesemia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypertension	Vascular disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Hyperthyroidism	Endocrine disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypertriglyceridemia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hyperuricemia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypoalbuminemia	Metabolism and nutrition disorders	EG0002 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypocalcemia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypoglycemia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypokalemia	Metabolism and nutrition disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypomagnesemia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0011 affected2 at risk EG0020 affected3 at risk EG003
Hyponatremia	Metabolism and nutrition disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Hypophosphatemia	Metabolism and nutrition disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Hypotension	Vascular disorders	EG0002 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Hypoxia	Respiratory, thoracic and mediastinal disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Infections and infestations - Other	Infections and infestations	EG0002 affected8 at risk EG0012 affected2 at risk EG0021 affected3 at risk EG003
INR increased	Investigations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Keratitis	Eye disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Leukoencephalopathy	Nervous system disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Lipase increased	Investigations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Lung infection	Infections and infestations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Lymphocyte count decreased	Investigations	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Mucositis oral	Gastrointestinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	EG0001 affected8 at risk EG0011 affected2 at risk EG0020 affected3 at risk EG003
Nausea	Gastrointestinal disorders	EG0002 affected8 at risk EG0011 affected2 at risk EG0021 affected3 at risk EG003
Neck pain	Musculoskeletal and connective tissue disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Neutrophil count decreased	Investigations	EG0002 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Non-cardiac chest pain	General disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Pain	General disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Palmar-plantar erythrodysesthesia syndrome	Skin and subcutaneous tissue disorders	EG0001 affected8 at risk EG0011 affected2 at risk EG0020 affected3 at risk EG003
Perineal pain	Reproductive system and breast disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Peripheral sensory neuropathy	Nervous system disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Pharyngeal mucositis	Respiratory, thoracic and mediastinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Photophobia	Eye disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Platelet count decreased	Investigations	EG0003 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Pneumonitis	Respiratory, thoracic and mediastinal disorders	EG0000 affected8 at risk EG0011 affected2 at risk EG0020 affected3 at risk EG003
Pruritus	Skin and subcutaneous tissue disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Purpura	Skin and subcutaneous tissue disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Rash maculo-papular	Skin and subcutaneous tissue disorders	EG0002 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Rectal pain	Gastrointestinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Reproductive system and breast disorders - Other	Reproductive system and breast disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Sepsis	Infections and infestations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Serum amylase increased	Investigations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Sinus tachycardia	Cardiac disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Skin and subcutaneous tissue disorders - Other	Skin and subcutaneous tissue disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Skin hypopigmentation	Skin and subcutaneous tissue disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Skin infection	Infections and infestations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Skin ulceration	Skin and subcutaneous tissue disorders	EG0001 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Toothache	Gastrointestinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Tracheal mucositis	Respiratory, thoracic and mediastinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Typhlitis	Gastrointestinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Upper gastrointestinal hemorrhage	Gastrointestinal disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0021 affected3 at risk EG003
Uterine hemorrhage	Reproductive system and breast disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Vomiting	Gastrointestinal disorders	EG0002 affected8 at risk EG0010 affected2 at risk EG0022 affected3 at risk EG003
Watering eyes	Eye disorders	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
Weight loss	Investigations	EG0000 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003
White blood cell decreased	Investigations	EG0002 affected8 at risk EG0010 affected2 at risk EG0020 affected3 at risk EG003

ID	Term
D007938	Leukemia
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma
D015456	Leukemia, Biphenotypic, Acute
D015470	Leukemia, Myeloid, Acute
D015479	Leukemia, Myelomonocytic, Acute
D007948	Leukemia, Monocytic, Acute
D004915	Leukemia, Erythroblastic, Acute
D007947	Leukemia, Megakaryoblastic, Acute

ID	Term
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D007945	Leukemia, Lymphoid
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases
D007951	Leukemia, Myeloid
D009196	Myeloproliferative Disorders
D001855	Bone Marrow Diseases

ID	Term
D000227	Adenine Nucleotides
D011685	Purine Nucleotides
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D001087	Arabinonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D009711	Nucleotides
D012265	Ribonucleotides
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines