bryostatin + fludarabine in treating patients with chronic lymphocytic leukemia or relapsed indolent non-hodgkin's lymphoma

Conditions: Leukemia; Lymphoma

Summary: 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.

Eligibility criteria:
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

Keywords: 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