Bryostatin 1 Plus Cladribine in Treating Patients With Relapsed Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase I Clinical Evaluation of Bryostatin 1 in Combination With 2-CdA in Patients With Relapsed CLL

Conditions
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Leukemia

Intervention / Treatment
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* Drug: bryostatin 1
* Drug: cladribine


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: bryostatin 1|nan|
|Drug: cladribine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia