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Bryostatin 1 Plus Fludarabine in Treating Patients With Chronic Lymphocytic Leukemia or Relapsed Indolent Non-Hodgkin's Lymphoma
This study has been completed.
First Received: May 2, 2000   Last Updated: July 23, 2008   History of Changes
Sponsors and Collaborators: Massey Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00005580
  Purpose

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 Intervention Phase
Leukemia
Lymphoma
Drug: bryostatin 1
Drug: fludarabine phosphate
Phase I

MedlinePlus related topics: Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma
Drug Information available for: Fludarabine Fludarabine monophosphate Bryostatin 1
U.S. FDA Resources
Study Type: Interventional
Study Design: 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

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: September 1998
Detailed Description:

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005580

Locations
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
Massey Cancer Center
Investigators
Study Chair: Steven Grant, MD Massey Cancer Center
  More Information

Additional Information:
Publications:
Study ID Numbers: CDR0000066433, MCV-CCHR-9801-2C, NCI-T97-0116
Study First Received: May 2, 2000
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00005580     History of Changes
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
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

Study placed in the following topic categories:
Antimetabolites
Leukemia, Lymphoid
Immunologic Factors
Large Granular Lymphocyte Leukemia
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Mantle Cell Lymphoma
Sezary Syndrome
Lymphoma, B-Cell, Marginal Zone
Mycosis Fungoides
Follicular Lymphoma
Lymphoma, B-Cell
Lymphoma, Small Cleaved-cell, Diffuse
Leukemia
Mycoses
Leukemia, Prolymphocytic
Cutaneous T-cell Lymphoma
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, T-Cell
Leukemia, B-cell, Chronic
Lymphoma
Prolymphocytic Leukemia
Immunoproliferative Disorders
Leukemia-Lymphoma, Adult T-Cell
Hairy Cell Leukemia
Adjuvants, Immunologic
Bryostatin 1
Fludarabine monophosphate
Immunosuppressive Agents
Recurrence

Additional relevant MeSH terms:
Antimetabolites
Leukemia, Lymphoid
Antimetabolites, Antineoplastic
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Therapeutic Uses
Lymphoma
Immunoproliferative Disorders
Neoplasms by Histologic Type
Immune System Diseases
Adjuvants, Immunologic
Bryostatin 1
Fludarabine monophosphate
Immunosuppressive Agents
Pharmacologic Actions
Lymphatic Diseases
Neoplasms
Fludarabine
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Leukemia, B-Cell

ClinicalTrials.gov processed this record on May 07, 2009