Homoharringtonine in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia

January 22, 2013 updated by: National Cancer Institute (NCI)

Phase I and Pilot Study of Subcutaneous Homoharringtonine in Chronic Myelogenous Leukemia

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

50

Phase

  • Phase 2

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
    • Texas
      • Houston, Texas, United States, 77030
        • M D Anderson 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

12 years and older (ADULT, OLDER_ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximum-tolerated dose (MTD) of homoharringtonine as assessed by the National Cancer Institute (NCI) Common Terminology Criteria (CTC)
Time Frame: 14 days
14 days
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.
Up to 6 years

Collaborators and Investigators

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

Sponsor

National Cancer Institute (NCI)

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

November 1, 1999

Primary Completion (ACTUAL)

September 1, 2005

Study Registration Dates

First Submitted

October 4, 2000

First Submitted That Met QC Criteria

January 26, 2003

First Posted (ESTIMATE)

January 27, 2003

Study Record Updates

Last Update Posted (ESTIMATE)

January 23, 2013

Last Update Submitted That Met QC Criteria

January 22, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCI-2012-02360
  • N01CM17003 (U.S. NIH Grant/Contract)
  • ID 99-032
  • CDR0000068237 (REGISTRY: PDQ (Physician Data Query))

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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