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Homoharringtonine in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia

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ClinicalTrials.gov Identifier: NCT00006364
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : January 23, 2013
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Study Description
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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
Childhood Chronic Myelogenous Leukemia Chronic Myelogenous Leukemia, BCR-ABL1 Positive Chronic Phase Chronic Myelogenous Leukemia Relapsing Chronic Myelogenous Leukemia Drug: omacetaxine mepesuccinate Other: pharmacological study Other: laboratory biomarker analysis Phase 2

Detailed Description:

OBJECTIVES:

I. 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.

IV. 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
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Study Type : Interventional  (Clinical Trial)
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 : November 1999
Actual Primary Completion Date : September 2005

Resource links provided by the National Library of Medicine


Arms and Interventions
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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 Name: pharmacological studies

Other: laboratory biomarker analysis
Correlative studies


Outcome Measures
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Primary Outcome Measures :
  1. Maximum-tolerated dose (MTD) of homoharringtonine as assessed by the National Cancer Institute (NCI) Common Terminology Criteria (CTC) [ Time Frame: 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 [ Time Frame: Up to 6 years ]
    Using a Bayesian approach.


Eligibility Criteria
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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00006364


Locations
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United States, Texas
M D Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Jorge Cortes M.D. Anderson Cancer Center
More Information
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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00006364    
Other Study ID Numbers: NCI-2012-02360
ID 99-032
N01CM17003 ( U.S. NIH Grant/Contract )
CDR0000068237 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: January 23, 2013
Last Verified: January 2013
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
 Hematologic Diseases
Homoharringtonine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action