Homoharringtonine in Treating Patients With Refractory Acute Promyelocytic Leukemia

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. PURPOSE: Phase I/II trial to study the effectiveness of homoharringtonine in treating patients who have refractory acute promyelocytic leukemia.

Detailed Description
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OBJECTIVES: Determine the safety of salvage therapy comprising homoharringtonine in patients with refractory acute promyelocytic leukemia. Determine the antileukemic efficacy of this drug in these patients. OUTLINE: Patients receive remission induction therapy comprising homoharringtonine (HH) IV continuously on days 1-14. Courses repeat every 4 weeks in the absence of unacceptable toxicity until a complete remission (CR) is achieved or the patient fails to respond after 3 courses. Patients who achieve a CR during induction therapy receive maintenance therapy comprising HH IV continuously on days 1-7. Maintenance treatment repeats every 4 weeks for a total of 12 courses in the absence of disease progression or unacceptable toxicity. Patients are followed at 4 weeks. PROJECTED ACCRUAL: A maximum of 20 patients will be accrued for this study.

Official Title
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A Phase I/II Open-Label Study Of The Intravenous Administration Of Homoharringtonine (CGX-635) Salvage Therapy For The Treatment Of Refractory Acute Promyelocytic Leukemia

Conditions
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Leukemia

Intervention / Treatment
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* Drug: homoharringtonine
* Procedure: chemotherapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of acute promyelocytic leukemia confirmed morphologically and by t(15;17) translocation or molecular polymerase chain reaction Refractory to tretinoin, anthracyclines, and arsenic-based therapy (including arsenic trioxide) and for which no other alternative therapy of higher priority is appropriate PATIENT CHARACTERISTICS: Age: 12 and over Performance status: Zubrod 0-3 Life expectancy: More than 4 weeks Hematopoietic: See Disease Characteristics Hepatic: Bilirubin no greater than 2.0 mg/dL ALT no greater than 3 times upper limit of normal Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: No New York Heart Association class III or IV heart disease No active ischemia No other uncontrolled cardiac condition (e.g., angina pectoris, cardiac arrhythmia, hypertension, or congestive heart failure) No myocardial infarction within the past 12 weeks Other: No other concurrent illness that would preclude study No other active malignancy No uncontrolled active infection No clinically significant screening serum chemistry results unless attributed to acute promyelocytic leukemia No medical or psychiatric condition that would preclude informed consent or study therapy HIV negative HTLV-I and HTLV-II negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Prior or concurrent leukapheresis allowed Chemotherapy: See Disease Characteristics At least 15 days since prior systemic chemotherapy unless leukemia progression necessitates early therapy No other concurrent systemic chemotherapy Endocrine therapy: Not specified Radiotherapy: Not specified Surgery: Not specified Other: Recovered from prior therapy At least 15 days since other prior antileukemic therapy unless leukemia progression necessitates early therapy No other concurrent antileukemic therapy

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: homoharringtonine|nan|
|Procedure: chemotherapy|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety by physical examinations, vital signs, laboratory studies (routine hematology, clinical chemistry, pharmacokinetics, urinalysis, chest x-ray, and EKG), and solicited and unsolicited adverse events |  |  | 
| Efficacy by response to treatment |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics |  |  | 
| Duration of treatment response |  |  | 
| Survival |  |  | 
| Induction mortality |  |  | 
| Hospitalizations |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent childhood acute myeloid leukemia, recurrent adult acute myeloid leukemia, adult acute promyelocytic leukemia (M3), childhood acute promyelocytic leukemia (M3), adult acute myeloid leukemia with t(15;17)(q22;q12)