Homoharringtonine in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia

Sponsor
National Cancer Institute (NCI) (NIH)
Overall Status
Completed
CT.gov ID
NCT00006364
Collaborator
(none)
50
1
1

Study Details

Study Description

Brief Summary

Phase II trial to study the effectiveness of homoharringtonine in treating patients who have chronic phase chronic myelogenous leukemia. Drugs used in chemotherapy, such as homoharringtonine, work in different ways to stop cancer cells from dividing so they stop growing or die

Condition or Disease Intervention/Treatment Phase
  • Drug: omacetaxine mepesuccinate
  • Other: pharmacological study
  • Other: laboratory biomarker analysis
Phase 2

Detailed Description

OBJECTIVES:
  1. Determine the maximum tolerated dose of homoharringtonine in patients with transformed phases of chronic myelogenous leukemia (CML). (Phase I completed as of 2/11/2004.) II. Determine the toxicity profile of this drug in these patients. III. Determine the response duration in patients with chronic phase CML treated with this drug.

  2. Compare the pharmacokinetics of this drug administered as a continuous infusion vs subcutaneously in these patients.

OUTLINE: This is a pilot, dose-escalation study. (Phase I completed as of 2/11/2004.)

Remission induction therapy: Patients receive remission induction therapy comprising homoharringtonine IV continuously over 24 hours on day 1 and then subcutaneously (SC) twice daily on days 2-14 for course 1. Subsequent courses of remission induction therapy comprise homoharringtonine SC twice daily on days 1-14. Treatment continues monthly for at least 2 courses.

Maintenance therapy: Patients with complete hematologic remission receive maintenance therapy comprising homoharringtonine SC twice daily on days 1-7 monthly for 3 years in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of homoharringtonine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 2 of 6 patients experience dose-limiting toxicity. An additional cohort of 25-30 patients with chronic phase chronic myelogenous leukemia receives remission induction and maintenance therapy as above at the MTD. (Phase I completed as of 2/11/2004.)

Patients are followed every 3 months.

PROJECTED ACCRUAL: A maximum of 50 patients will be accrued for this study.

Study Design

Study Type:
Interventional
Actual Enrollment :
50 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase I and Pilot Study of Subcutaneous Homoharringtonine in Chronic Myelogenous Leukemia
Study Start Date :
Nov 1, 1999
Actual Primary Completion Date :
Sep 1, 2005

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (omacetaxine mepesuccinate)

Remission induction therapy: Patients receive remission induction therapy comprising homoharringtonine IV continuously over 24 hours on day 1 and then subcutaneously (SC) twice daily on days 2-14 for course 1. Subsequent courses of remission induction therapy comprise homoharringtonine SC twice daily on days 1-14. Treatment continues monthly for at least 2 courses. Maintenance therapy: Patients with complete hematologic remission receive maintenance therapy comprising homoharringtonine SC twice daily on days 1-7 monthly for 3 years in the absence of disease progression or unacceptable toxicity.

Drug: omacetaxine mepesuccinate
Given IV or SC
Other Names:
  • CGX-635
  • homoharringtonine
  • Other: pharmacological study
    Correlative studies
    Other Names:
  • pharmacological studies
  • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. Maximum-tolerated dose (MTD) of homoharringtonine as assessed by the National Cancer Institute (NCI) Common Terminology Criteria (CTC) [14 days]

    2. Complete hematologic remission (CHR) defined as at least 4 weeks of bone marrow (less than 5% blasts) and peripheral blood with WBC < 10 x 10^9/L and no peripheral blasts, promyelocytes, or myelocytes [Up to 6 years]

      Using a Bayesian approach.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Diagnosis of chronic phase chronic myelogenous leukemia (CML), as defined by the following:

    • Less than 15% blasts in the peripheral blood (PB) or bone marrow (BM)

    • Less than 20% basophils in the PB or BM

    • Platelet count > 100,000/mm^3 (unless related to therapy)

    • Absence of clonal evolution*

    • Philadelphia chromosome- OR BCR/ABL-positive disease by cytogenetics, fluorescence in situ hybridization, or polymerase chain reaction

    • Failed prior therapy with imatinib mesylate, as defined by any of the following:

    • Failed to achieve or have lost a complete hematologic remission after 3 months of therapy

    • Failed to achieve or have lost at least a minimal cytogenetic response after 6 months of therapy

    • Failed to achieve or have lost a major or complete cytogenetic response after 12 months of therapy

    • Unable to tolerate imatinib mesylate despite adequate dose adjustment

    • Failed no more than 2 prior treatment regimens (in addition to imatinib mesylate)

    • Treatment with hydroxyurea is not considered one regimen

    • Ineligible for known regimens or protocols of higher efficacy or priority

    • Performance status - Zubrod 0-2

    • At least 2 months

    • Bilirubin no greater than 2.0 mg/dL

    • Creatinine less than 2.0 mg/dL

    • No New York Heart Association class III or IV heart disease

    • Not pregnant or nursing

    • Fertile patients must use effective contraception

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 M D Anderson Cancer Center Houston Texas United States 77030

    Sponsors and Collaborators

    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Jorge Cortes, M.D. Anderson Cancer Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    National Cancer Institute (NCI)
    ClinicalTrials.gov Identifier:
    NCT00006364
    Other Study ID Numbers:
    • NCI-2012-02360
    • ID 99-032
    • N01CM17003
    • CDR0000068237
    First Posted:
    Jan 27, 2003
    Last Update Posted:
    Jan 23, 2013
    Last Verified:
    Jan 1, 2013

    Study Results

    No Results Posted as of Jan 23, 2013