Clinical trial NCT00030355: Homoharringtonine in Treating Patients With Refractory Acute Promyelocytic Leukemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Leukemia
Keywords: 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)
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 0
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
measure: Efficacy by response to treatment
Secondary outcomes:
measure: Pharmacokinetics
measure: Duration of treatment response
measure: Survival
measure: Induction mortality
measure: Hospitalizations
Other outcomes:
Locations:
city: Houston
country: United States
facility: M. D. Anderson Cancer Center at University of Texas
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Jorge Cortes, MD
role: STUDY_CHAIR
References: