Bryostatin 1 and High Dose Cytarabine in Treating Patients With Refractory or Relapsed Leukemia or 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 and high dose cytarabine in treating patients with refractory or relapsed acute myelocytic or acute lymphocytic leukemia, chronic myelogenous leukemia or refractory or relapsed lymphoblastic lymphoma.
|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 High-Dose 1-Beta-D-Arabinofuranosylcytosine (HiDAC) in Patients With Refractory Leukemia|
|Study Start Date:||September 1997|
|Study Completion Date:||May 2001|
|Primary Completion Date:||May 2001 (Final data collection date for primary outcome measure)|
OBJECTIVES: I. Define the maximum tolerated dose (MTD) of bryostatin 1 administered before and after high dose cytarabine in patients with refractory or relapsed acute myelocytic leukemia or acute lymphocytic leukemia, chronic myelogenous leukemia, or refractory or relapsed lymphoblastic lymphoma. II. Describe the toxic effects of bryostatin 1 and high dose cytarabine in these patients. III. Describe the time course of bryostatin 1 induced modulation of leukemic blast total protein kinase C (PKC) activity. IV. Describe bryostatin 1 pharmacokinetics. V. Correlate bryostatin 1 induced modulation of leukemic cell PKC activity or leukemic cell maturation with high dose cytarabine mediated apoptosis.
OUTLINE: This is a dose escalation study. Patients receive bryostatin 1 by continuous infusion over 24 hours on day 1. One hour after completion of bryostatin 1, patients receive high dose cytarabine IV over 3 hours every 12 hours on days 2-4. Patients again receive cytarabine over 3 hours every 12 hours on days 9-11, followed 1 hour later by bryostatin 1 by continuous infusion over 24 hours beginning on day 11. Patients achieving complete remission may receive up to 4 courses of consolidation chemotherapy. Consolidation chemotherapy is the same as induction chemotherapy except patients receive only 2 doses of cytarabine after day 1 completion of bryostatin and only 2 doses of cytarabine prior to the day 11 dose of bryostatin. Patients achieving partial remission may receive a second course of induction chemotherapy. In the absence of dose limiting toxicity in the first 3 patients treated, subsequent cohorts of 6 patients receive escalating doses of bryostatin 1 on the same schedule. If dose limiting toxicity occurs in 2 of 6 patients at a given dose level, then dose escalation ceases and the current dose is defined as the maximum tolerated dose. Patients are followed every 6 months until death.
PROJECTED ACCRUAL: A total of 12-50 patients will be accrued for this study.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00003079
|United States, New York|
|New York Presbyterian Hospital - Cornell Campus|
|New York, New York, United States, 10021|
|United States, Texas|
|University of Texas - MD Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|United States, Virginia|
|Massey Cancer Center|
|Richmond, Virginia, United States, 23298-0037|
|Study Chair:||Steven Grant, MD||Massey Cancer Center|