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

Lymphoma Clinical Trial

Official title:

Phase I Study of Bryostatin 1 (NSC 339555) and Fludarabine in Patients With Chronic Lymphocytic Leukemia and Indolent Non-Hodgkin's Lymphoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00005580
• Other study ID #: CDR0000066433
• Secondary ID: P30CA016059MCV-C
• Status: Completed
• Phase: Phase 1
• First received: May 2, 2000
• Last updated: February 23, 2010
• Start date: September 1998
• Est. completion date: August 2006

Study information

• Verified date: February 2010
• Source: Virginia Commonwealth University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 54
• Est. completion date: August 2006
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Factorial Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• bryostatin 1

• fludarabine phosphate

Locations

Country	Name	City	State
United States	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

Sponsors (2)

Lead Sponsor	Collaborator
Virginia Commonwealth University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 indol — View Citation