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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00005580
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : February 24, 2010
National Cancer Institute (NCI)
Information provided by:
Virginia Commonwealth University

Brief 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.

Condition or disease Intervention/treatment Phase
Leukemia Lymphoma Drug: bryostatin 1 Drug: fludarabine phosphate Phase 1

Detailed Description:


  • 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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 54 participants
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Bryostatin 1 (NSC 339555) and Fludarabine in Patients With Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin's Lymphoma
Study Start Date : September 1998
Actual Primary Completion Date : August 2006
Actual Study Completion Date : August 2006

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • 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



  • 18 and over

Performance status:

  • Zubrod 0-2

Life expectancy:

  • Not specified


  • Granulocyte count at least 1,000/mm3
  • Platelet count at least 75,000/mm3
  • Hemoglobin at least 8 g/dL
  • Coombs negative


  • AST/ALT no greater than 2.5 times upper limit of normal
  • Bilirubin no greater than 2 mg/mL


  • Creatinine clearance at least 40 mL/min


  • 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


Biologic therapy:

  • No concurrent systemic immunoglobulin therapy
  • No prior bone marrow or peripheral stem cell transplantation


  • See Disease Characteristics
  • At least 3 weeks since prior systemic chemotherapy

Endocrine therapy:

  • No concurrent systemic glucocorticoid therapy


  • Not specified


  • Not specified


  • No other concurrent anticancer therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00005580

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United States, New York
New York Presbyterian Hospital - Cornell Campus
New York, New York, United States, 10021
United States, Pennsylvania
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States, 19111
United States, Virginia
Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
Sponsors and Collaborators
Virginia Commonwealth University
National Cancer Institute (NCI)
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Study Chair: Steven Grant, MD Massey Cancer Center
Publications of Results:
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Responsible Party: National Cancer Institute Identifier: NCT00005580    
Other Study ID Numbers: CDR0000066433
P30CA016059 ( U.S. NIH Grant/Contract )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: February 24, 2010
Last Verified: February 2010
Keywords provided by Virginia Commonwealth University:
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
Additional relevant MeSH terms:
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Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Fludarabine phosphate
Bryostatin 1
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic