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

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