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

NCT ID: NCT00005580

Last Updated: 2010-02-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1998-09-30
• Study Completion Date: 2006-08-31

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.

Conditions

Leukemia; Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Interventions

bryostatin 1

Intervention Type: DRUG

fludarabine phosphate

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Virginia Commonwealth University

OTHER

Sponsor Role: lead

Principal Investigators

Steven Grant, MD

Role: STUDY_CHAIR

Massey Cancer Center

Locations

New York Presbyterian Hospital - Cornell Campus

New York, New York, United States

Fox Chase Cancer Center

Philadelphia, Pennsylvania, United States

Massey Cancer Center

Richmond, Virginia, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 17020988 (View on PubMed)

Other Identifiers

P30CA016059

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MCV-CCHR-9801-2C

Identifier Type: -

Identifier Source: secondary_id

NCI-T97-0116

Identifier Type: -

Identifier Source: secondary_id

CDR0000066433

Identifier Type: -

Identifier Source: org_study_id