Bryostatin 1 and High Dose Cytarabine in Treating Patients With Refractory or Relapsed Leukemia or Lymphoma

February 15, 2010 updated by: Virginia Commonwealth University

Phase I Study of Bryostatin 1 (NSC 339555) and High-Dose 1-Beta-D-Arabinofuranosylcytosine (HiDAC) in Patients With Refractory Leukemia

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 Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • New York
      • New York, New York, United States, 10021
        • New York Presbyterian Hospital - Cornell Campus
    • Texas
      • Houston, Texas, United States, 77030
        • University of Texas - MD Anderson Cancer Center
    • Virginia
      • Richmond, Virginia, United States, 23298-0037
        • Massey Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

DISEASE CHARACTERISTICS: Histologically confirmed primary refractory or relapsed acute myelocytic leukemia (AML) or acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML) in blast crisis, or refractory or relapsed lymphoblastic lymphoma Priority is given to patients previously treated with conventional high dose cytarabine regimen without bryostatin 1 Eligible if previously failed a conventional high dose cytarabine regimen or if underwent subsequent high dose therapy with bone marrow/stem cell transplantation with curative intent

PATIENT CHARACTERISTICS: Age: 18 and over (must be 60 or under if receiving higher dose of cytarabine) Performance status: Karnofsky 60-100% Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Bilirubin no greater than 2.0 mg/dL (bilirubin no greater than 3.0 mg/dL and conjugated bilirubin no greater than 0.5 mg/dL if Gilbert's disease and predominantly unconjugated hyperbilirubinemia present) AST no greater than 2.5 times upper limit of normal (ULN) Alkaline phosphatase no greater than 2.5 times ULN Renal: Creatinine clearance at least 40 mL/min (at least 60 mL/min if receiving higher dose of cytarabine) Pulmonary: No clinically significant pulmonary disease Other: Not pregnant No patients who are poor medical risks because of nonmalignant systemic disease No serious, active, uncontrolled infection No prior or concurrent medical status that would make assessing cortical or cerebellar neurologic toxicity difficult

PRIOR CONCURRENT THERAPY: Recovery from the major toxic effects of prior therapy required Biologic therapy: See Disease Characteristics Chemotherapy: See Disease Characteristics At least 24 hours since prior chemotherapy with hydroxyurea At least 3 weeks since other prior systemic chemotherapy No prior clinically significant cerebellar toxicity due to cytarabine Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Factorial Assignment
  • Masking: None (Open Label)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Virginia Commonwealth University

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Steven Grant, MD, Massey Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 1997

Primary Completion (Actual)

May 1, 2001

Study Completion (Actual)

May 1, 2001

Study Registration Dates

First Submitted

May 2, 2000

First Submitted That Met QC Criteria

May 26, 2004

First Posted (Estimate)

May 27, 2004

Study Record Updates

Last Update Posted (Estimate)

February 17, 2010

Last Update Submitted That Met QC Criteria

February 15, 2010

Last Verified

February 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CDR0000065773
  • P30CA016059 (U.S. NIH Grant/Contract)
  • MCV-MCC-9612-2E
  • NCI-T97-0011

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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