Romidepsin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This phase II trial is studying how well romidepsin works in treating patients with relapsed or refractory acute myeloid leukemia. Drugs used in chemotherapy, such as romidepsin, work in different ways to stop tumor cells from dividing so they stop growing or die.

Detailed Description
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PRIMARY OBJECTIVES: I. Determine the complete and partial response rate in patients with relapsed or refractory acute myeloid leukemia treated with FR901228 (depsipeptide). II. Determine the toxicity of this drug in these patients. III. Correlate clinical response with specific cytogenetic abnormalities in patients treated with this drug. OUTLINE: Patients are stratified according to the presence of a specific chromosomal abnormality (t[8;21] vs inv 16 vs t[15;17] vs absence of these chromosomal abnormalities). Patients receive romidepsin IV over 4 hours on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Official Title
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A Phase 2 Study of Depsipeptide in Patients With Relapsed or Refractory AML

Conditions
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Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities, Adult Acute Myeloid Leukemia With Del(5q), Adult Acute Myeloid Leukemia With Inv(16)(p13;q22), Adult Acute Myeloid Leukemia With t(15;17)(q22;q12), Adult Acute Myeloid Leukemia With t(16;16)(p13;q22), Adult Acute Myeloid Leukemia With t(8;21)(q22;q22), Adult Acute Promyelocytic Leukemia (M3), Recurrent Adult Acute Myeloid Leukemia

Intervention / Treatment
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* Drug: romidepsin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed acute myeloid leukemia (AML) defined by the WHO classification Initial diagnosis with either of the following: Bone marrow or peripheral blood myeloblasts of at least 20%, Recurring genetic abnormalities (e.g., t[8;21], inv 16, or t[16;16]) and Bone marrow blast percentage less than 20% Relapsed or refractory disease defined by 1 of the following: Under 60 years of age and in second relapse or greater, Over 60 years of age and in first relapse, Acute promyelocytic leukemia that has relapsed despite prior tretinoin and arsenic therapy, Primary refractory AML for which no standard therapy exists Patients who are over 60 years of age with previously untreated disease and who refuse conventional chemotherapy are eligible Patients who are over 60 years of age and in first relapse and poor medical candidates for reinduction chemotherapy or who refuse conventional chemotherapy are eligible Not medically appropriate for OR refused curative bone marrow or stem cell transplantation No CNS leukemia ECOG 0-2 OR Karnofsky 60-100% LVEF at least 40% by MUGA QTc interval less than 500 msec by EKG No myocardial infarction within the past 3 months No symptomatic congestive heart failure No unstable angina pectoris No cardiac arrhythmia Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No prior allergic reactions attributed to compounds of similar chemical or biological composition to FR901228 (depsipeptide) No concurrent uncontrolled illness No psychiatric illness or social situation that would preclude study compliance No ongoing or active infection At least 4 weeks since prior autologous stem cell or bone marrow transplantation No prior allogeneic stem cell or bone marrow transplantation No concurrent biologic agents At least 2 weeks since prior chemotherapy (6 weeks for mitomycin and nitrosoureas) No concurrent chemotherapy, concurrent hydroxyurea allowed during the first course of study therapy to control hyperleukocytosis No concurrent radiotherapy Recovered from prior therapy At least 4 weeks since prior investigational agents No concurrent combination antiretroviral therapy for HIV-positive patients No other concurrent investigational agents No concurrent drugs known to have histone deacetylase inhibitor activity (e.g., sodium valproate) No other concurrent antineoplastic agents No prior FR901228 (depsipeptide) At least 2 weeks since prior radiotherapy

Ages Eligible for Study
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Minimum Age: 18 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: Treatment<br>Patients receive romidepsin IV over 4 hours on days 1, 8, and 15. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. | Drug: romidepsin<br>* Given IV<br>* Other names: Istodax;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (complete and partial) |  | Up to 7 years | 
| Adverse events, measured using National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2.0 |  | Up to 7 years |