Homoharringtonine Plus Low-Dose Cytarabine in Treating Patients With Newly Diagnosed Chronic Myelogenous Leukemia in Chronic Phase

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00003694

Collaborator

(none)

Enrollment

Location

Arm

Study Details

Study Description

Brief Summary

Phase II trial to study the effectiveness of homoharringtonine plus low-dose cytarabine in treating patients who have newly diagnosed chronic phase chronic myelogenous leukemia. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myelogenous Leukemia, BCR-ABL1 Positive Chronic Phase Chronic Myelogenous Leukemia	Drug: omacetaxine mepesuccinate Drug: cytarabine Other: laboratory biomarker analysis	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

To estimate the hematologic and cytogenetic response rate of newly diagnosed patients with BCR/ABL (+) chronic myelogenous leukemia (CML) treated with combined homoharringtonine (omacetaxine mepesuccinate) and low dose cytarabine.
To estimate the toxicity of these two drugs given in combination in a cooperative group setting.

SECONDARY OBJECTIVES:

To assess duration of hematological response and incidence of hematological progression for all patients.
To assess duration of cytogenetic response in patients continuing protocol therapy beyond the initial nine months.
To use quantitative Southern blot monitoring of blood samples to monitor molecular response rates in patients entered onto CALGB treatment studies for CML.
To compare quantitative Southern blot results of blood samples with marrow cytogenetics at the time of complete molecular response.
To use RT-PCR to monitor the frequency of residual disease in patients who have achieved a complete blood Southern blot and marrow cytogenetic response (elimination of BCR/ABL positivity by Southern blot and absence of the Philadelphia chromosome by cytogenetics).

OUTLINE:

Patients receive cytarabine and homoharringtonine concurrently by continuous intravenous infusion for 7 days. Courses repeat every 28 days. Patients receive a minimum of 9 courses of therapy in the absence of disease progression and unacceptable toxicity. Patients who are major cytogenetic responders at 9 months may continue therapy or switch to interferon. Minor cytogenetic responders are switched to interferon, and nonresponders are removed from therapy and given the option to switch to interferon.

Patients are followed every 6 months for 10 years.

Study Design

Study Type:

Interventional

Actual Enrollment :

60 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase II Study of Newly Diagnosed Patients With BCR/ABL (+) Chronic Myelogenous Leukemia Treated With Combined Homoharringtonine (NSC #141633) and Low-Dose Cytarabine

Study Start Date :

Mar 1, 1999

Actual Primary Completion Date :

Aug 1, 2003

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (omacetaxine mepesuccinate, cytarabine) Patients receive cytarabine and homoharringtonine concurrently by continuous intravenous infusion for 7 days. Courses repeat every 28 days. Patients receive a minimum of 9 courses of therapy in the absence of disease progression and unacceptable toxicity. Patients who are major cytogenetic responders at 9 months may continue therapy or switch to interferon. Minor cytogenetic responders are switched to interferon, and nonresponders are removed from therapy and given the option to switch to interferon.	Drug: omacetaxine mepesuccinate Given IV Other Names: CGX-635 homoharringtonine Drug: cytarabine Given IV Other Names: ARA-C arabinofuranosylcytosine arabinosylcytosine Cytosar-U cytosine arabinoside Other: laboratory biomarker analysis Correlative studies

Arm

Intervention/Treatment

Experimental: Treatment (omacetaxine mepesuccinate, cytarabine)

Drug: omacetaxine mepesuccinate

Given IV

Other Names:

CGX-635

homoharringtonine

Drug: cytarabine

Given IV

Other Names:

ARA-C

arabinofuranosylcytosine

arabinosylcytosine

Cytosar-U

cytosine arabinoside

Other: laboratory biomarker analysis

Correlative studies

Outcome Measures

Primary Outcome Measures

Complete cytogenetic, major cytogenetic, and hematologic response rate [Up to 9 months]
Two separate single-stage Fleming designs will be used to test hypotheses regarding the major cytogenetic response rate and the complete cytogenetic response rate. Calculated and presented with their 95% confidence intervals.

Secondary Outcome Measures

Toxicity rates as assessed by Common Terminology Criterial version 2.0 [Up to 9 months]
Duration of hematological response [Up to 10 years]
Described with Kaplan-Meier curves.
Time to hematological progression [Up to 10 years]
Described with Kaplan-Meier curves.

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Histologic diagnosis of chronic myelogenous leukemia (CML) in chronic phase; patients in either accelerated or blastic phases are not eligible; clonal cytogenetic evolution alone does not exclude patients
Patients must meet one or more of the following criteria:
Cytogenetically determined Philadelphia chromosome (Ph+)
BCR/ABL protein detectable by immunoblotting
Polymerase chain reaction (PCR) positive fusion transcripts for BCR/ABL
BCR/ABL translocation present by fluorescence in situ hybridization (FISH)
Registration within eight weeks of the diagnosis and confirmation of Ph+ or BCR/ABL+ CML
No more than eight weeks of prior hydroxyurea therapy
No previous therapy with homoharringtonine (HHT)
No prior treatment for CML with agents other than hydroxyurea; thus, prior treatment for CML with agents such as interferon, busulfan or cytarabine will render patients ineligible
Must not be a candidate for an early allogeneic bone marrow transplant; potential transplant candidates must be counseled about alternative donor transplants and must decline that treatment option
ECOG performance status 0-2
Non-pregnant and non-nursing; treatment under this protocol would expose an unborn child to significant risks; women and men of reproductive potential should agree to use an effective means of birth control
Bilirubin =< x upper limit of normal
Creatinine =< 1.5 mg/dl