Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting
Text Size

Homoharringtonine in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00006364
First received: October 4, 2000
Last updated: January 22, 2013
Last verified: January 2013
History of Changes
  Purpose
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 Intervention 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

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I and Pilot Study of Subcutaneous Homoharringtonine in Chronic Myelogenous Leukemia

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum-tolerated dose (MTD) of homoharringtonine as assessed by the National Cancer Institute (NCI) Common Terminology Criteria (CTC) [ Time Frame: 14 days ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: No ]
    Using a Bayesian approach.
Enrollment: 50
Study Start Date: November 1999
Primary Completion Date: September 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility
Ages Eligible for Study:   12 Years and older   (Child, Adult, Senior)
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00006364

Locations
United States, Texas
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
  More Information

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00006364     History of Changes
Other Study ID Numbers: NCI-2012-02360  ID 99-032  N01CM17003  CDR0000068237 
Study First Received: October 4, 2000
Last Updated: January 22, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
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
Harringtonines
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on September 27, 2016