Bryostatin + Fludarabine in Treating Patients With Chronic Lymphocytic Leukemia or Relapsed Indolent Non-Hodgkin's Lymphoma
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.
Drug: bryostatin 1
Drug: fludarabine phosphate
|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|
|Study Start Date:||September 1998|
|Study Completion Date:||August 2006|
|Primary Completion Date:||August 2006 (Final data collection date for primary outcome measure)|
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00005580
|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|
|Study Chair:||Steven Grant, MD||Massey Cancer Center|