Bryostatin + Fludarabine in Treating Patients With Chronic Lymphocytic Leukemia or Relapsed Indolent Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. PURPOSE: Phase I trial to study the effectiveness of bryostatin 1 plus fludarabine in treating patients who have chronic lymphocytic leukemia or relapsed, indolent non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Determine the toxic effects and maximum tolerated dose of bryostatin 1 and fludarabine in patients with symptomatic or advanced chronic lymphocytic leukemia or relapsed indolent non-Hodgkin's lymphoma. Monitor apoptosis, differentiation, and protein kinase C activity in leukemic lymphocytes exposed in vivo to bryostatin 1 and fludarabine. Observe the antitumor activity of this combination therapy in these patients. OUTLINE: This is a dose-escalation, multicenter study. Patients are assigned to one of two treatment groups. Group I: Patients receive bryostatin 1 IV over 24 hours followed by fludarabine IV over 30 minutes daily on days 1-5. Group II: Patients receive fludarabine IV over 30 minutes daily on days 1-5 followed by bryostatin 1 IV over 24 hours. In both groups, courses repeat every 4 weeks for patients with stable or responding disease. Cohorts of 3-6 patients receive escalating doses of fludarabine and bryostatin 1 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. Once the MTD for fludarabine is determined, the dose of bryostatin 1 is escalated. PROJECTED ACCRUAL: Approximately 30-60 patients will be accrued for this study within 3 years.

Official Title
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Phase I Study of Bryostatin 1 (NSC 339555) and Fludarabine in Patients With Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin's Lymphoma

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Drug: bryostatin 1
* Drug: fludarabine phosphate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed chronic lymphocytic leukemia Stage I (symptomatic or with bulky lymphadenopathy) Stage II, III, or IV Prior chemotherapy allowed, including fludarabine or other purine nucleoside analog therapy OR Histologically confirmed indolent non-Hodgkin's lymphoma Progressive or relapsed following chemotherapy Includes the following histologies: B-cell chronic lymphocytic leukemia/prolymphocytic leukemia/lymphomas Lymphoplasmacytoid lymphoma (Waldenstrom's)/immunocytoma Mantle cell lymphoma Follicular lymphoma Small cell Mixed small and large cell Diffuse (predominately small cell type) Marginal zone B-cell lymphoma Extranodal (MALT-type with or without monocytoid B-cells) Provisional subtype: nodal (with or without monocytoid B-cells) Provisional entity: splenic marginal zone lymphoma (with or without villous lymphocytes) Hairy cell leukemia Peripheral T-cell and NK-cell neoplasms T-cell chronic lymphocytic leukemia/polylymphocytic leukemia Large granular lymphocyte leukemia T-cell type NK-cell type Mycosis fungoides/Sezary's syndrome (cutaneous T-cell lymphoma) No CNS disease PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Zubrod 0-2 Life expectancy: Not specified Hematopoietic: Granulocyte count at least 1,000/mm3 Platelet count at least 75,000/mm3 Hemoglobin at least 8 g/dL Coombs negative Hepatic: AST/ALT no greater than 2.5 times upper limit of normal Bilirubin no greater than 2 mg/mL Renal: Creatinine clearance at least 40 mL/min Other: No concurrent neurologic condition No other concurrent medical condition that would preclude study Not pregnant or nursing Fertile patients must use effective contraception during and for 3 months after study PRIOR CONCURRENT THERAPY: Biologic therapy: No concurrent systemic immunoglobulin therapy No prior bone marrow or peripheral stem cell transplantation Chemotherapy: See Disease Characteristics At least 3 weeks since prior systemic chemotherapy Endocrine therapy: No concurrent systemic glucocorticoid therapy Radiotherapy: Not specified Surgery: Not specified Other: No other concurrent anticancer 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
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: bryostatin 1|nan|
|Drug: fludarabine phosphate|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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recurrent cutaneous T-cell non-Hodgkin lymphoma, Waldenstrom macroglobulinemia, stage I chronic lymphocytic leukemia, stage II chronic lymphocytic leukemia, stage III chronic lymphocytic leukemia, stage IV chronic lymphocytic leukemia, refractory chronic lymphocytic leukemia, T-cell large granular lymphocyte leukemia, B-cell chronic lymphocytic leukemia, refractory hairy cell leukemia, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult T-cell leukemia/lymphoma, prolymphocytic leukemia, recurrent mantle cell lymphoma, recurrent mycosis fungoides/Sezary syndrome, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma