Combination Chemotherapy in Treating Patients With Acute Promyelocytic Leukemia

Sponsor

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins (Other)

Overall Status

Completed

CT.gov ID

NCT00276601

Collaborator

National Cancer Institute (NCI) (NIH)

Locations

104

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.

PURPOSE: This phase II trial is studying how well giving combination chemotherapy works in treating patients with acute promyelocytic leukemia.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: arsenic trioxide Drug: cytarabine Drug: daunorubicin hydrochloride Drug: mercaptopurine Drug: methotrexate Drug: tretinoin	Phase 2

Detailed Description

OBJECTIVES:

Determine, preliminarily, the safety of incorporating arsenic trioxide (ATO) into cytarabine and daunorubicin hydrochloride-based consolidation therapy followed by tretinoin maintenance therapy in patients receiving induction tretinoin and daunorubicin hydrochloride with acute promyelocytic leukemia (APL) induced into remission with tretinoin and daunorubicin hydrochloride.
Determine, preliminarily, the efficacy of this strategy in inducing and maintaining molecular remissions in patients treated with this regimen.

OUTLINE: This is a pilot, multicenter study.

Induction therapy: Patients receive oral tretinoin twice daily on days 1-60 and daunorubicin hydrochloride IV on days 4, 6, and 8. Patients are evaluated between days 60-67 and proceed to consolidation therapy.
Consolidation therapy: Patients receive cytarabine IV continuously on days 1-3, daunorubicin hydrochloride IV on days 1-3, and arsenic trioxide IV over 1-2 hours once daily, 5 days a week, beginning on day 8 and continuing for 6 weeks. Patients with clinical and/or cytogenic, but not molecular, remission receive additional arsenic trioxide once daily, 5 days a week, for 30 doses (6 weeks). Patients achieving clinical and molecular remission after completion of 6 or 12 weeks of arsenic trioxide proceed to maintenance therapy.
Maintenance therapy: Patients receive oral tretinoin once daily on days 1-15. Treatment repeats every 3 months for 8 courses (2 years).

After completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Official Title:

A Pilot Study of Arsenic Trioxide-Based Consolidation Therapy for the Primary Treatment of Acute Promyelocytic Leukemia

Study Start Date :

Oct 1, 2004

Actual Primary Completion Date :

Dec 1, 2007

Actual Study Completion Date :

Jun 1, 2013

Outcome Measures

Primary Outcome Measures

Disease-free survival at 2 and 5 years after study completion []
Safety of arsenic trioxide following cytarabine and anthracycline immediately after study completion []

Secondary Outcome Measures

Validate peripheral blood real-time PCR for minimal disease monitoring as measured by real-time PCR for PML-RARalpha monthly for two years after study completion []

Eligibility Criteria

Criteria

Ages Eligible for Study:

5 Years to 74 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Diagnosis of acute promyelocytic leukemia (APL) by morphologic and flow cytometric documentation (high orthogonal light scatter, lack of HLA-DR expression)
Patients with classical APL as well as the microgranular variant (M3V) are eligible
In cases where the diagnosis is unclear, consultation with a hematopathologist is required before enrolling the patient in the study
Patients found to have cytogenetic abnormalities that do not produce the PML-RARα gene rearrangement will be removed from study and will not be included in data analysis

PATIENT CHARACTERISTICS:

Patients will not be excluded because of performance status or comorbid disease
Premenopausal female patients must have a negative pregnancy test

PRIOR CONCURRENT THERAPY:

No prior chemotherapy for APL except hydroxyurea

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama	United States	35294
2	University of Florida Shands Cancer Center	Gainesville	Florida	United States	32610-0232
3	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia	United States	30342
4	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland	United States	21201
5	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland	United States	21231-2410
6	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska	United States	68198-3330
7	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania	United States	15232