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