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

Phase 2
12 Years
Not Enrolling
Childhood Chronic Myelogenous Leukemia, Chronic Myelogenous Leukemia, BCR-ABL1 Positive, Chronic Phase Chronic Myelogenous Leukemia, Relapsing Chronic Myelogenous Leukemia

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Trial Information

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


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

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.

Inclusion Criteria:

- Diagnosis of chronic phase chronic myelogenous leukemia (CML), as defined by the

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Maximum-tolerated dose (MTD) of homoharringtonine as assessed by the National Cancer Institute (NCI) Common Terminology Criteria (CTC)

Outcome Time Frame:

14 days

Safety Issue:


Principal Investigator

Jorge Cortes

Investigator Role:

Principal Investigator

Investigator Affiliation:

M.D. Anderson Cancer Center


United States: Food and Drug Administration

Study ID:




Start Date:

November 1999

Completion Date:

Related Keywords:

  • Childhood Chronic Myelogenous Leukemia
  • Chronic Myelogenous Leukemia, BCR-ABL1 Positive
  • Chronic Phase Chronic Myelogenous Leukemia
  • Relapsing Chronic Myelogenous Leukemia
  • Leukemia
  • Leukemia, Myeloid
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive
  • Leukemia, Myeloid, Chronic-Phase



M D Anderson Cancer Center Houston, Texas  77030