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NCT00372619 · CITED IN SOURCE DOCUMENTS

Clofarabine and Cytarabine in Treating Young Patients With Refractory or Relapsed Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase
PHASE1, PHASE2
Status at capture
COMPLETED
Registry last update
2017-06-05

RATIONALE: Drugs used in chemotherapy, such as clofarabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with cytarabine and to see how well they work in treating young patients with refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia. (Phase I closed to enrollment as of 09/16/09)

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What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

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

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outcome · POSTED

Safety and Tolerability as Measured by CTCAE v3.0

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outcome · POSTED

Correlate the Expression of Apoptosis Specific Genes

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part
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.
healthy Volunteers
false
maximum Age
30 Years
minimum Age
1 Year
sex
ALL
std Ages
  1. CHILD
  2. ADULT
Treatment arms and interventions
arm Groups
  1. description
    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.
    intervention Names
    1. Drug: clofarabine
    2. Drug: cytarabine
    3. Drug: methotrexate
    4. Other: laboratory biomarker analysis
    label
    Clofarabine 40 mg/m² to assess feasibility in ALL patients.
    type
    EXPERIMENTAL
  2. description
    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.
    intervention Names
    1. Drug: clofarabine
    2. Drug: cytarabine
    3. Drug: methotrexate
    4. Other: laboratory biomarker analysis
    label
    Clofarabine 40 mg/m² to assess feasibility in AML patients.
    type
    EXPERIMENTAL
  3. description
    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.
    intervention Names
    1. Drug: clofarabine
    2. Drug: cytarabine
    3. Drug: methotrexate
    4. Other: laboratory biomarker analysis
    label
    Clofarabine 52 mg/m² to assess feasibility in ALL patients.
    type
    EXPERIMENTAL
  4. description
    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.
    intervention Names
    1. Drug: clofarabine
    2. Drug: cytarabine
    3. Drug: methotrexate
    4. Other: laboratory biomarker analysis
    label
    Clofarabine 52 mg/m² to assess efficacy in ALL patients.
    type
    EXPERIMENTAL
  5. description
    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.
    intervention Names
    1. Drug: clofarabine
    2. Drug: cytarabine
    3. Drug: methotrexate
    4. Other: laboratory biomarker analysis
    label
    Clofarabine 52 mg/m² to assess feasibility in AML patients.
    type
    EXPERIMENTAL
  6. description
    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.
    intervention Names
    1. Drug: clofarabine
    2. Drug: cytarabine
    3. Drug: methotrexate
    4. Other: laboratory biomarker analysis
    label
    Clofarabine 52 mg/m² to assess efficacy in AML patients
    type
    EXPERIMENTAL
  7. description
    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.
    intervention Names
    1. Drug: clofarabine
    2. Drug: cytarabine
    3. Drug: methotrexate
    4. Other: laboratory biomarker analysis
    label
    Clofarabine 52 mg/m² to assess efficacy - ambiguous lineage pt
    type
    EXPERIMENTAL
interventions
  1. arm Group Labels
    1. Clofarabine 40 mg/m² to assess feasibility in ALL patients.
    2. Clofarabine 40 mg/m² to assess feasibility in AML patients.
    3. Clofarabine 52 mg/m² to assess efficacy - ambiguous lineage pt
    4. Clofarabine 52 mg/m² to assess efficacy in ALL patients.
    5. Clofarabine 52 mg/m² to assess efficacy in AML patients
    6. Clofarabine 52 mg/m² to assess feasibility in ALL patients.
    7. Clofarabine 52 mg/m² to assess feasibility in AML patients.
    description
    Given IV for 5 days
    name
    clofarabine
    other Names
    1. Cl-F-Ara-A
    2. CAFdA
    3. 2-Chloro-9-(2-deoxy-2-fluoro-beta-D-arabinofuranosyl)-9H-purin-6-amine
    4. Clolar
    5. Evoltra
    6. NSC# 606,869
    7. IND # 73,789
    type
    DRUG
  2. arm Group Labels
    1. Clofarabine 40 mg/m² to assess feasibility in ALL patients.
    2. Clofarabine 40 mg/m² to assess feasibility in AML patients.
    3. Clofarabine 52 mg/m² to assess efficacy - ambiguous lineage pt
    4. Clofarabine 52 mg/m² to assess efficacy in ALL patients.
    5. Clofarabine 52 mg/m² to assess efficacy in AML patients
    6. Clofarabine 52 mg/m² to assess feasibility in ALL patients.
    7. Clofarabine 52 mg/m² to assess feasibility in AML patients.
    description
    Given IV
    name
    cytarabine
    other Names
    1. Cytosine arabinoside
    2. Ara-C
    3. Cytosar
    4. NSC #063878
    type
    DRUG
  3. arm Group Labels
    1. Clofarabine 40 mg/m² to assess feasibility in ALL patients.
    2. Clofarabine 40 mg/m² to assess feasibility in AML patients.
    3. Clofarabine 52 mg/m² to assess efficacy - ambiguous lineage pt
    4. Clofarabine 52 mg/m² to assess efficacy in ALL patients.
    5. Clofarabine 52 mg/m² to assess efficacy in AML patients
    6. Clofarabine 52 mg/m² to assess feasibility in ALL patients.
    7. Clofarabine 52 mg/m² to assess feasibility in AML patients.
    description
    Given intrathecally or IT age based dosage
    name
    methotrexate
    other Names
    1. MTX
    2. amethopterin
    3. Trexall
    4. NSC #000740
    type
    DRUG
  4. arm Group Labels
    1. Clofarabine 40 mg/m² to assess feasibility in ALL patients.
    2. Clofarabine 40 mg/m² to assess feasibility in AML patients.
    3. Clofarabine 52 mg/m² to assess efficacy - ambiguous lineage pt
    4. Clofarabine 52 mg/m² to assess efficacy in ALL patients.
    5. Clofarabine 52 mg/m² to assess efficacy in AML patients
    6. Clofarabine 52 mg/m² to assess feasibility in ALL patients.
    7. Clofarabine 52 mg/m² to assess feasibility in AML patients.
    name
    laboratory biomarker analysis
    type
    OTHER
Study design
allocation
NON_RANDOMIZED
intervention Model
PARALLEL
masking Info
masking
NONE
primary Purpose
TREATMENT
Enrollment
count
74
type
ACTUAL
Registered outcome plans (not posted results)
primary Outcomes
  1. description
    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)).
    measure
    Overall Response (CR for ALL Patients), (CR + CRp for AML Patients)
    time Frame
    2 cycles or up to 84 days
secondary Outcomes
  1. description
    Number of participants with at least one grade 3 or higher adverse event during therapy.
    measure
    Safety and Tolerability as Measured by CTCAE v3.0
    time Frame
    End of therapy
  2. description
    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).
    measure
    Correlate the Expression of Apoptosis Specific Genes
    time Frame
    End of therapy
Full study description
brief Summary
RATIONALE: Drugs used in chemotherapy, such as clofarabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of clofarabine when given together with cytarabine and to see how well they work in treating young patients with refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia. (Phase I closed to enrollment as of 09/16/09)
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.
Source references
Source notices and limitations
    Discovery and provenance
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        0033&amp;version=HealthProfessional&amp;language=English'); return(false);">Level of evidence B4</a>] The COG <a href="/clinicaltrials/NCT00372619">AAML0523 (NCT00372619)</a> trial evaluated the combination of clofarabine plus high-dose cytarabine in patients with relapsed AML. The response rate was 48% and the OS rate was 46%,
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      Childhood Acute Myeloid Leukemia Treatment (PDQ®)–Health Professional Version
      source update dates
      1. context
        Updated: April 15, 2025
        datetime
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        April 15, 2025

    Preserved source evidence · Not medical advice