Purpose:
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.
Study summary:
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.
Criteria:
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