A Phase II Open-Label Study of High-Dose Cytarabine and Clofarabine in Adult Patients With Refractory or Relapsed Acute Myelogenous Leukemia or Refractory or Relapsed Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as cytarabine and clofarabine, 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 II trial is studying clofarabine when given together with cytarabine to see how well they work in treating patients with refractory or relapsed acute myeloid leukemia or acute lymphoblastic leukemia.

Detailed Description
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OBJECTIVES: Determine the response rate in adult patients with relapsed or refractory acute myeloid leukemia or acute lymphoblastic leukemia treated with high-dose cytarabine followed by clofarabine. OUTLINE: This is an open-label phase II study. Patients are stratified according to diagnosis (acute myeloid leukemia vs acute lymphoblastic leukemia Phase II: Patients receive high-dose cytarabine followed by clofarabine (at the dose determined in phase I) on days 1-3. After completion of study treatment, patients are followed periodically for up to 5 years. PROJECTED ACCRUAL: A total of 39 patients were accrued for this study.

Official Title
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A Phase II Open-Label Study of High-Dose Cytarabine and Clofarabine in Adult Patients With Refractory or Relapsed Acute Myelogenous Leukemia or Refractory or Relapsed Acute Lymphoblastic Leukemia

Conditions
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Leukemia

Intervention / Treatment
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* Drug: clofarabine
* Drug: cytarabine


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Pathologic confirmation of acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) No M3 AML Meets 1 of the following criteria: In first relapse In second relapse after a second complete remission (CR) that lasted ≥ 3 months Refractory to initial induction therapy No symptomatic CNS involvement PATIENT CHARACTERISTICS: ECOG performance status ≤ 2 Creatinine < 2 mg/dL Bilirubin ≤ 2 mg/dL AST and ALT ≤ 4 times upper limit of normal Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 2 weeks after completing study treatment Ejection fraction ≥ 45% by echocardiogram No active, uncontrolled systemic infection considered opportunistic, life-threatening, or clinically significant No psychiatric disorders that would interfere with giving consent, study participation, or follow-up procedures No other severe concurrent disease that would preclude study treatment PRIOR CONCURRENT THERAPY: At least 1 week since prior therapy and recovered No other concurrent chemotherapy Hydroxyurea to control WBC count before starting study treatment allowed No concurrent corticosteroids unless used for diseases other than leukemia No concurrent palliative radiotherapy No concurrent growth factors (e.g., epoetin alfa, filgrastim [G-CSF], or sargramostim [GM-CSF]) in patients with AML

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: high-dose cytarabine and clofarabine<br>high-dose cytarabine (2000 milligram/meter squared/day) administered intravenously over 3 hours followed by clofarabine administered intravenously over 2 hours daily for 5 consecutive days | Drug: clofarabine<br> <br> Drug: cytarabine<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure Patient Response to High-dose Cytarabine Followed by Clofarabine in Adult Patients With Relapsed or Refractory AML | Response to the therapy is measured by a defined improvement in Neutrophil and platlet counts, along with improved cellularity of bone marrow biopsy (>20% with maturation of all cell lines), <5% blasts, auer rods must not be detectable and extramedullary leukemia or soft tissue involvment must not be present. | 5 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute basophilic leukemia, adult acute eosinophilic leukemia, adult erythroleukemia (M6a), adult pure erythroid leukemia (M6b), adult acute megakaryoblastic leukemia (M7), adult acute minimally differentiated myeloid leukemia (M0), adult acute monoblastic leukemia (M5a), adult acute monocytic leukemia (M5b), adult acute myeloblastic leukemia with maturation (M2), adult acute myeloblastic leukemia without maturation (M1), adult acute myelomonocytic leukemia (M4)