Homoharringtonine in Treating Patients With Chronic Phase Chronic Myelogenous Leukemia

NCT ID: NCT00006364

Last Updated: 2013-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-11-30

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

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.

Conditions

Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Relapsing Chronic Myelogenous Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

omacetaxine mepesuccinate

Intervention Type: DRUG

Given IV or SC

pharmacological study

Intervention Type: OTHER

Correlative studies

laboratory biomarker analysis

Intervention Type: OTHER

Correlative studies

Interventions

omacetaxine mepesuccinate

Given IV or SC

Intervention Type: DRUG

pharmacological study

Correlative studies

Intervention Type: OTHER

laboratory biomarker analysis

Correlative studies

Intervention Type: OTHER

Other Intervention Names

CGX-635; homoharringtonine; pharmacological studies

Eligibility 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

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jorge Cortes

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Other Identifiers

ID 99-032

Identifier Type: -

Identifier Source: secondary_id

N01CM17003

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CDR0000068237

Identifier Type: REGISTRY

Identifier Source: secondary_id

NCI-2012-02360

Identifier Type: -

Identifier Source: org_study_id