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

Virginia Commonwealth University54 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Leukemia Lymphoma

Interventions

bryostatin 1DRUG

fludarabine phosphateDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (3)

New York Presbyterian Hospital - Cornell Campus

New York, New York, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Massey Cancer Center

Richmond, Virginia, United States

Data from ClinicalTrials.gov

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