Bryostatin 1 and Cytarabine in Treating Patients With Relapsed Acute Myelogenous Leukemia

Phase II Study Of Bryostatin 1 (NSC 339555) And High-Dose 1-B-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 II trial to study the effectiveness of combining bryostatin 1 with cytarabine in treating patients who have relapsed primary acute myelogenous leukemia.

Study Overview

• Status: Completed
• Conditions: Leukemia
• Intervention / Treatment: Drug: cytarabine; Drug: bryostatin 1

Detailed Description

OBJECTIVES:

• Determine the response rate in patients with primary acute myelogenous leukemia in first relapse treated with bryostatin 1 and high-dose cytarabine.
• Determine the toxic effects of this regimen in these patients.
• Determine the relapse-free survival and overall survival of patients treated with this regimen.

OUTLINE: This is a multicenter study.

• Induction: Patients receive bryostatin 1 IV over 24 hours on days 1 and 11. Patients also receive high-dose cytarabine IV over 3 hours every 12 hours for 4 infusions on days 2-3 and days 9-10.

Patients who achieve a major response receive a second course of induction therapy.

• Consolidation: Patients who achieve complete remission receive bryostatin 1 IV over 24 hours on days 1 and 10 and high-dose cytarabine IV over 3 hours every 12 hours for 2 infusions on days 2 and 9. Treatment continues for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Patients who achieve a response and subsequently relapse may receive additional induction and consolidation therapy at the discretion of the investigator.

Patients are followed every 6 months.

PROJECTED ACCRUAL: A total of 15-46 patients will be accrued for this study.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • New York Weill Cornell Cancer Center at Cornell University
    • New York, New York, United States, 10032
      • Herbert Irving Comprehensive Cancer Center at Columbia University
  • Texas
    • Houston, Texas, United States, 77030-4009
      • University of Texas - MD Anderson Cancer Center
  • Virginia
    • Richmond, Virginia, United States, 23298-0037
      • Massey Cancer Center at Virginia Commonwealth University

Participation Criteria

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 acute myelogenous leukemia (AML) in first relapse after a remission of at least 3 months duration

• No secondary AML, including the following:

  • Therapy-related AML
  • AML arising from myelodysplastic syndromes or similar hematological conditions
• No Philadelphia chromosome or other evidence of a (9;21) translocation
• Ineligible for potentially curative allogeneic stem cell transplantation

PATIENT CHARACTERISTICS:

Age:

• 18 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Bilirubin no greater than 1.5 times upper limit of normal (ULN) (patients with Gilbert's disease or unconjugated hyperbilirubinemia may have bilirubin no greater than 3.0 mg/dL with conjugated bilirubin no greater than 0.5 mg/dL)
• AST/ALT no greater than 2 times ULN

Renal:

• Creatinine no greater than 1.5 times ULN

Pulmonary:

• No clinically significant pulmonary disease

Other:

• No clinically significant cytarabine-related cerebellar toxicity
• No nonmalignant systemic disease that causes poor medical risk
• No active, uncontrolled, serious infection
• No medical condition that would preclude study participation
• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy:

• See Disease Characteristics
• No prior allogeneic stem cell transplantation

Chemotherapy:

• At least 2 weeks since prior systemic chemotherapy (24 hours for hydroxyurea) and recovered

Endocrine therapy:

• Not specified

Radiotherapy:

• Not specified

Surgery:

• Not specified

Other:

• Recovered from all prior therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Steven Grant, MD, Massey Cancer Center

Study record dates

Study Major Dates

• Study Start: July 1, 2001
• Primary Completion (Actual): September 1, 2004
• Study Completion (Actual): June 1, 2005

Study Registration Dates

• First Submitted: June 6, 2001
• First Submitted That Met QC Criteria: February 5, 2003
• First Posted (Estimate): February 6, 2003

Study Record Updates

• Last Update Posted (Estimate): March 1, 2010
• Last Update Submitted That Met QC Criteria: February 26, 2010
• Last Verified: February 1, 2010

More Information

Terms related to this study

• Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities; adult acute myeloid leukemia with inv(16)(p13;q22); adult acute myeloid leukemia with t(15;17)(q22;q12); adult acute myeloid leukemia with t(16;16)(p13;q22); adult acute myeloid leukemia with t(8;21)(q22;q22); recurrent adult acute myeloid leukemia
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Adjuvants, Immunologic; Cytarabine; Bryostatin 1
• Other Study ID Numbers: CDR0000068679; P30CA016059 (U.S. NIH Grant/Contract); MCV-MCC-4710; NCI-4710