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

Primary Purpose

Leukemia, Lymphoma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
bryostatin 1
fludarabine phosphate
Sponsored by
Virginia Commonwealth University
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • New York Presbyterian Hospital - Cornell Campus
  • Fox Chase Cancer Center
  • Massey Cancer Center

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
May 2, 2000
Last Updated
February 23, 2010
Sponsor
Virginia Commonwealth University
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT00005580
Brief Title
Bryostatin + Fludarabine in Treating Patients With Chronic Lymphocytic Leukemia or Relapsed Indolent Non-Hodgkin's Lymphoma
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 Type
Interventional

2. Study Status

Record Verification Date
February 2010
Overall Recruitment Status
Completed
Study Start Date
September 1998 (undefined)
Primary Completion Date
August 2006 (Actual)
Study Completion Date
August 2006 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Virginia Commonwealth University
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphoma
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
54 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
bryostatin 1
Intervention Type
Drug
Intervention Name(s)
fludarabine phosphate

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Steven Grant, MD
Organizational Affiliation
Massey Cancer Center
Official's Role
Study Chair
Facility Information:
Facility Name
New York Presbyterian Hospital - Cornell Campus
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Fox Chase Cancer Center
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19111
Country
United States
Facility Name
Massey Cancer Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298-0037
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
17020988
Citation
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. doi: 10.1158/1078-0432.CCR-05-2730.
Results Reference
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Learn more about this trial

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

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