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

Sponsor:	Virginia Commonwealth University
Collaborator:	National Cancer Institute (NCI)
Information provided by:	Virginia Commonwealth University
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

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety Study Intervention Model: Factorial Assignment Masking: 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

Resource links provided by NLM:

MedlinePlus related topics: Acute Lymphocytic Leukemia Cancer Chronic Lymphocytic Leukemia Leukemia Lymphoma

Drug Information available for: Fludarabine Fludarabine monophosphate Bryostatin 1

U.S. FDA Resources

Further study details as provided by Virginia Commonwealth University:

Enrollment:	54
Study Start Date:	September 1998
Study Completion Date:	August 2006
Primary Completion Date:	August 2006 (Final data collection date for primary outcome measure)

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

Virginia Commonwealth University

National Cancer Institute (NCI)

Investigators

Study Chair:

Steven Grant, MD

Massey Cancer Center

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

Publications:

Roberts JD, Smith MR, Feldman EJ, Cragg L, Millenson MM, Roboz GJ, Honeycutt C, Thune R, Padavic-Shaller K, Carter WH, Ramakrishnan V, Murgo AJ, Grant S. Phase I study of bryostatin 1 and fludarabine in patients with chronic lymphocytic leukemia and indolent (non-Hodgkin's) lymphoma. Clin Cancer Res. 2006 Oct 1;12(19):5809-16.

Responsible Party:	National Cancer Institute
ClinicalTrials.gov Identifier:	NCT00005580 History of Changes
Other Study ID Numbers:	CDR0000066433, P30CA016059, MCV-CCHR-9801-2C, NCI-T97-0116
Study First Received:	May 2, 2000
Last Updated:	February 23, 2010
Health Authority:	United States: Federal Government

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:

Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Leukemia, B-Cell
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Bryostatin 1
Fludarabine monophosphate

Fludarabine
Vidarabine
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Immunosuppressive Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on February 12, 2012