fr901228 in treating patients with hematologic cancer

Conditions: Leukemia; Lymphoma

Summary: 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.

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.

Eligibility 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

Keywords: 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