Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Homoharringtonine in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II Treatment Completed 12 and over NCI MDA-ID-99032 MDA-FDR001783, NCI-T99-0044, T99-0044, NCT00006364

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.)
2. Determine the toxicity profile of this drug in these patients.
3. Determine the response duration in patients with chronic phase CML treated with this drug.
4. Compare the pharmacokinetics of this drug administered as a continuous infusion vs subcutaneously in these patients.

Entry Criteria

Disease Characteristics:

• 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/mm³ (unless related to therapy)
  • Absence of clonal evolution*

   [Note: * Patients with variant Philadelphia chromosome or deletions of chromosome Y (-Y) are eligible if there is no chromosomal change representing 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

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• See Disease Characteristics

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• See Disease Characteristics

Patient Characteristics:

Age:

• 12 and over

Performance status:

• Zubrod 0-2

Life expectancy:

• At least 2 months

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Bilirubin no greater than 2.0 mg/dL

Renal:

• Creatinine less than 2.0 mg/dL

Cardiovascular:

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

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception

Expected Enrollment

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

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.

Quintás-Cardama A, Kantarjian H, Garcia-Manero G, et al.: Phase I/II study of subcutaneous homoharringtonine in patients with chronic myeloid leukemia who have failed prior therapy. Cancer 109 (2): 248-55, 2007.[PUBMED Abstract]

Quintas-Cardama A, Cortes J, Verstovsek S, et al.: Subcutaneous (SC) homoharringtonine (HHT) for patients (pts) with chronic myelogenous leukemia (CML) in chronic phase (CP) after imatinib mesylate failure. [Abstract] Blood 106 (11): A-4839, 2005 .

Trial Contact Information

Trial Lead Organizations

M. D. Anderson Cancer Center at University of Texas

Jorge Cortes, MD, Protocol chair		Ph: 713-794-5783; 800-392-1611 Email: jcortes@mdanderson.org

Registry Information
Official Title		Phase I and Pilot Study of Subcutaneous Homoharringtonine in Chronic Myelogenous Leukemia (CML)
Trial Start Date		1999-11-17
Registered in ClinicalTrials.gov		NCT00006364
Date Submitted to PDQ		2000-08-24
Information Last Verified		2005-11-04
NCI Grant/Contract Number		P30-CA16672, U01-CA62461

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