Leukemia
Conditions
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
Brief 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.
Detailed description
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.
Interventions
DRUGbryostatin 1
DRUGcladribine
Sponsors
National Cancer Institute (NCI)
Barbara Ann Karmanos Cancer Institute
Study design
Primary purpose
TREATMENT
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Countries
United States
Outcome results
None listed