DIFFERENTIATION THERAPY OF CHRONIC MYELOGENOUS LEUKEMIA

Project: Research project

Project Details

Description

We propose to accomplish a phase II pilot study of the differentiating agent Bryostatin 1 in chronic myelogenous leukemia. Bryostatin 1 is a macrocyclic lactone isolated from a marine Bryozoan which functions by activating protein kinase C. We have demonstrated that it induces the differentiation and inhibits the growth of CML blast cells in vitro. In animals it inhibits the growth of specific tumor types. These results led to phase I testing of Bryostatin 1 in humans which defined a dose and schedule for the administration of Bryostatin 1 and demonstrated that Bryostatin 1 had a limited set of side effects which do not involve the hematopoietic system. The aims of this pilot trial are: (1) to determine whether the infusion Bryostatin 1 into patients with CML induces the biochemical or biologic differentiation of CML blast cells; (2) to determine the best markers of this differentiated phenotype and the time course of their induction ; (3) to examine whether ability of blast cells to respond in vitro to Bryostatin 1 correlates with the in vivo response; (4) to determine in this single arm study whether Bryostatin 1 induces complete or partial remissions in patients with this disease and determine whether this response correlates with in vivo differentiation; and (5) to accomplish Bryostatin 1 pharmacology using a novel assay. For this pilot study we propose to treat 18 CML patients on a once a week schedule for six months at a dose of 25 ug/m2 infused over one hour. CML patients in the chronic phase of the disease off chemotherapy for one month will be eligible for this study. The trial will not be stopped because of lack of immediate visible clinical effects since it is possible that differentiating agents will have a slow cumulative effect. This pilot study should yield important information about whether Bryostatin 1 is capable of inducing the differentiation of CML cells in patients and bringing about a lasting clinical response in this disease. The important biochemical, clinical, and pharmacologic pilot data obtained should greatly assist in the design of a standard Phase II study.
StatusFinished
Effective start/end date4/25/953/31/97

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.