FR901228 in Treating Patients With Myelodysplastic Syndrome, Acute Myeloid Leukemia, or Non-Hodgkin's Lymphoma

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 II trial to study the effectiveness of FR901228 in treating patients who have myelodysplastic syndrome, acute myeloid leukemia, or non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Determine the pattern of adverse clinical experience in patients with myelodysplastic syndrome, acute myeloid leukemia, or intermediate-grade or follicular non-Hodgkin's lymphoma treated with FR901228 (depsipeptide). Determine the disease response in patients treated with this drug. Determine the pharmacokinetic and pharmacodynamic correlates of this drug, including measurement of serum plasma levels, H3 and H4 acetylation, apoptosis induction, differentiation, and multidrug-resistant (MDR) phenotype expression in these patients. OUTLINE: Patients receive FR901228 (depsipeptide) IV over 4 hours on days 1 and 5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients are followed monthly. PROJECTED ACCRUAL: A total of 12 patients will be accrued for this study within 1 year.

Official Title
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A Pilot Study Of FR901228, Or Depsipeptide (NSC #630176) For Adult Patients With Advanced Hematologic Cancers

Conditions
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Leukemia, Lymphoma, Myelodysplastic Syndromes, Myelodysplastic/Myeloproliferative Neoplasms

Intervention / Treatment
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* Drug: romidepsin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: One of the following diagnoses: Histologically confirmed refractory or relapsed acute myeloid leukemia (AML) Failed anthracycline-based chemotherapy Ineligible for or refused allogeneic stem cell transplantation Elderly patients with newly diagnosed AML Ineligible for or refused standard chemotherapy Histologically confirmed high-risk myelodysplastic syndromes Eligible subtypes include: Refractory anemia with excess blasts (RAEB) RAEB in transformation Chronic myelomonocytic leukemia Ineligible for or refused allogeneic bone marrow transplantation Histologically confirmed intermediate-grade non-Hodgkin's lymphoma (NHL) Relapsed after high-dose therapy OR Ineligible for allogeneic or autologous stem cell transplantation Evaluable lesions by radiologic study or physical examination Histologically confirmed follicular NHL Progressed after anthracycline-based chemotherapy and rituximab Evaluable lesions by radiologic study or physical examination NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of indolent or aggressive lymphoma will replace the former terminology of low, intermediate, or high grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age 18 and over Performance status Karnofsky 60-100% Life expectancy Not specified Hematopoietic Not specified Hepatic Bilirubin no greater than 1.5 mg/dL (unless due to Gilbert's syndrome) SGOT and SGPT less than 2 times upper limit of normal Renal Creatinine no greater than 1.5 mg/dL OR Creatinine clearance at least 60 mL/min Cardiovascular Cardiac ejection fraction greater than 50% No cardiac hypertrophy No known conduction heart disease No New York Heart Association class III or IV heart disease that would make it difficult to assess patient during study participation No significant prior heart disease No significant prior secondary or tertiary heart block No significant prior atrial or ventricular arrhythmia requiring therapeutic intervention or antiarrhythmics for rate control Pulmonary No severe debilitating pulmonary disease that would make it difficult to assess patient during study participation Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 1 month after study participation Potassium ≥ 4.0 mmol/L (supplementation allowed) Magnesium ≥ 2.0 mg/dL (supplementation allowed) No other concurrent active malignancy except basal cell skin cancer No other concurrent significant co-morbidity that would make it difficult to assess patient during study participation PRIOR CONCURRENT THERAPY: Biologic therapy See Disease Characteristics At least 2 weeks since prior epoetin alfa or filgrastim (G-CSF) At least 4 weeks since prior cytokines No concurrent immunotherapy Chemotherapy See Disease Characteristics At least 4 weeks since prior systemic chemotherapy No other concurrent chemotherapy Endocrine therapy Not specified Radiotherapy At least 4 weeks since prior radiotherapy No concurrent radiotherapy Surgery Not specified Other No other concurrent investigational agents No concurrent drugs that may prolong the QTc interval FR901228 (depsipeptide) may be administered after a 5-half-life washout period following the use of these drugs

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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recurrent adult acute myeloid leukemia, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, chronic myelomonocytic leukemia, recurrent grade 3 follicular lymphoma, previously treated myelodysplastic syndromes, secondary myelodysplastic syndromes, untreated adult acute myeloid leukemia, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, atypical chronic myeloid leukemia, BCR-ABL1 negative, myelodysplastic/myeloproliferative neoplasm, unclassifiable, adult acute myeloid leukemia with t(8;21)(q22;q22), adult acute myeloid leukemia with t(16;16)(p13;q22), adult acute myeloid leukemia with inv(16)(p13;q22), adult acute myeloid leukemia with 11q23 (MLL) abnormalities, adult acute myeloid leukemia with t(15;17)(q22;q12)