Homoharringtonine in Treating Patients With Refractory Acute Promyelocytic Leukemia

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

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.

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.

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