FR901228 in Treating Patients With Hematologic Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase I trial to study the effectiveness of FR901228 in treating patients who have hematologic cancer.

Detailed Description
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OBJECTIVES: Determine the in vivo biologic effect of FR901228 (depsipeptide) in patients with chronic lymphocytic leukemia, small lymphocytic lymphoma, acute myeloid leukemia, or acute lymphoblastic leukemia. Determine the pharmacokinetics and cellular pharmacodynamics of this drug in these patients. Determine any preliminary anti-tumor activity of this drug in these patients. OUTLINE: This is a dose-decreasing, multicenter study. Patients are stratified according to disease (chronic lymphocytic leukemia and small lymphocytic lymphoma vs acute myeloid leukemia and acute lymphoblastic leukemia). Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1, 8, and 15. Treatment repeats every 4 weeks for up to 1 year in the absence of disease progression or unacceptable toxicity. Cohorts of 10 patients per stratum receive decreasing doses of FR901228 until the minimal active dose is determined. If 5 or more patients show clinical or biological response, the subsequent cohort is treated at a lower dose. If fewer than 5 patients respond, the subsequent cohort is treated at a higher dose. PROJECTED ACCRUAL: A minimum of 20 patients (10 per stratum) will be accrued for this study.

Official Title
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A Phase I Study of Depsipeptide in Selected Hematologic Malignancies (NSC 630176)

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Drug: romidepsin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of one of the following hematologic malignancies: Chronic lymphocytic leukemia (CLL) Small lymphocytic lymphoma (SLL) (including Waldenstrom's macroglobulinemia) Acute myeloid leukemia (AML) Acute lymphoblastic leukemia (ALL) Stratum I (CLL and SLL): Received at least one prior therapy containing a purine analog OR Received another form of therapy (including alkylating agents) due to history of severe autoimmune disease, requirement for chronic corticosteroid, or other contraindication to purine analog therapy Stratum II (AML and ALL): Primary refractory or relapsed leukemia within the past year that is not amenable to curative therapy OR Untreated or previously treated poor-risk leukemia defined by any of the following: 65 years of age and over Poor-risk candidates for aggressive chemotherapy Poor-risk cytogenetics (for AML, karyotype abnormalities other than t(8;21), inv(16), t(15;17)) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: At least 12 weeks Hematopoietic: Stratum I only: No uncontrolled autoimmune hemolytic anemia No idiopathic thrombocytopenic purpura Stratum II only: WBC no greater than 10,000/mm^3 OR WBC no greater than 40,000/mm^3 that is stable for at least 1 week (may be sustained by hydroxyurea through the first week of study) Hepatic: Bilirubin no greater than 1.5 mg/dL ALT and AST no greater than 3 times upper limit of normal Renal: Creatinine less than 2.0 mg/dL Cardiovascular: Ejection fraction at least 50% by MUGA No myocardial infarction or unstable angina within the past 6 months No prior unstable ventricular or supraventricular cardiac arrhythmias Other: HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other medical or psychiatric problem that would preclude study Stratum I only: No active infection requiring oral or IV antibiotics PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics At least 28 days since prior chemotherapy (except hydroxyurea) At least 6 weeks since prior nitrosoureas At least 8 weeks since prior UCN-01 (unless plasma UCN-01 level less than 1 uM) Endocrine therapy: See Disease Characteristics Radiotherapy: At least 28 days since prior radiotherapy Surgery: At least 28 days since prior major surgery

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: romidepsin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Waldenström macroglobulinemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, refractory chronic lymphocytic leukemia, untreated adult acute lymphoblastic leukemia, untreated adult acute myeloid leukemia, recurrent small lymphocytic lymphoma