Combination Chemotherapy in Treating Patients With Acute Promyelocytic Leukemia

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00276601
• Other study ID #: J0442, CDR0000449985
• Secondary ID: P30CA006973JHOC-
• Status: Completed
• Phase: Phase 2
• First received: January 12, 2006
• Last updated: April 16, 2014
• Start date: October 2004
• Est. completion date: June 2013

Study information

• Verified date: April 2014
• Source: Sidney Kimmel Comprehensive Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. completion date: June 2013
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 5 Years to 74 Years

Eligibility

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-RARa 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

Study Design

Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Promyelocytic, Acute

Intervention

Drug:
• arsenic trioxide

• cytarabine

• daunorubicin hydrochloride

• mercaptopurine

• methotrexate

• tretinoin

Locations

Country	Name	City	State
United States	Blood and Marrow Transplant Group of Georgia	Atlanta	Georgia
United States	Greenebaum Cancer Center at University of Maryland Medical Center	Baltimore	Maryland
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	Comprehensive Cancer Center at University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Florida Shands Cancer Center	Gainesville	Florida
United States	UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Omaha	Nebraska
United States	Hillman Cancer Center at University of Pittsburgh Cancer Institute	Pittsburgh	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Sidney Kimmel Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease-free survival at 2 and 5 years after study completion			No
Primary	Safety of arsenic trioxide following cytarabine and anthracycline immediately after study completion			Yes
Secondary	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			No