bryostatin 1 plus cladribine in treating patients with relapsed chronic lymphocytic leukemia

Conditions: Leukemia

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. combining more than one drug may kill more tumor cells. purpose: this phase i trial is studying the side effects and best dose of cladribine when given with bryostatin 1 in treating patients with relapsed chronic lymphocytic leukemia.

objectives: * determine the maximum tolerated dose of cladribine when administered after bryostatin 1 in patients with relapsed chronic lymphocytic leukemia. * determine the qualitative and quantitative toxic effects of this regimen in these patients. outline: this is a multicenter, dose-escalation study of cladribine. patients receive bryostatin 1 iv continuously on days 1-3 immediately followed by cladribine iv continuously on days 4-8. courses repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. patients who achieve complete remission (cr) receive 2 additional courses past cr. cohorts of 3-6 patients receive escalating dose levels of cladribine until the maximum tolerated dose (mtd) is determined. the mtd is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. patients are followed at 3 weeks. projected accrual: a minimum of 15 patients will be accrued for this study.

Eligibility criteria:
disease characteristics: * diagnosis of relapsed chronic lymphocytic leukemia * intermediate- or high-risk (stage i-iv) disease * intermediate-risk patients must have active disease, defined by at least 1 of the following criteria: * presence of any 1 of the following disease-related b symptoms: * 10% or more loss of body weight within the past 6 months * extreme fatigue * fever greater than 100 degrees fahrenheit without evidence of infection * night sweats * massive (greater than 6 cm below left costal margin) or progressive splenomegaly * massive (greater than 10 cm in longest diameter) or progressive lymphadenopathy * progressive lymphocytosis with an increase of more than 50% over a 2-month period or anticipated doubling time of less than 12 months * progressive bone marrow failure as manifested by the development or worsening of anemia and/or thrombocytopenia * autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroids * failed 1-2 prior front-line regimens * failed prior fludarabine * ineligible for any known treatment of higher potential efficacy patient characteristics: age: * 18 and over performance status: * zubrod 0-2 life expectancy: * at least 12 weeks hematopoietic: * see disease characteristics * absolute neutrophil count at least 1,000/mm\^3 * platelet count at least 50,000/mm\^3 hepatic: * bilirubin less than 1.5 mg/dl * transaminases less than 2.5 times normal renal: * creatinine less than 1.5 mg/dl or * creatinine clearance at least 60 ml/min cardiovascular: * no history of severe coronary artery disease, cardiomyopathy, uncontrolled congestive heart failure, or arrhythmias neurologic: * no prior drug-related neurotoxicity * no other neurologic disorder other: * not pregnant or nursing * fertile patients must use effective barrier or non-hormonal contraception during and for 2 months after study participation * no hiv infection * no aids prior concurrent therapy: biologic therapy: * no prior bone marrow transplantation chemotherapy: * see disease characteristics * at least 4 weeks since prior chemotherapy (8 weeks for mitomycin or nitrosoureas) and recovered endocrine therapy: * see disease characteristics * no concurrent steroids * no concurrent hormonal contraceptives radiotherapy: * at least 4 weeks since prior radiotherapy and recovered surgery: * not specified other: * no other concurrent therapy

Keywords: stage i chronic lymphocytic leukemia stage ii chronic lymphocytic leukemia stage iii chronic lymphocytic leukemia stage iv chronic lymphocytic leukemia refractory chronic lymphocytic leukemia