Clinical trial NCT00276601: Combination Chemotherapy in Treating Patients With Acute Promyelocytic Leukemia
Official title: A Pilot Study of Arsenic Trioxide-Based Consolidation Therapy for the Primary Treatment of Acute Promyelocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia
Keywords: untreated adult acute myeloid leukemia
untreated childhood acute myeloid leukemia and other myeloid malignancies
adult acute promyelocytic leukemia (M3)
childhood acute promyelocytic leukemia (M3)
adult acute myeloid leukemia with t(15;17)(q22;q12)
Lead sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-01-13
Sex: ALL
Minimum age (years): 5
Maximum age (years): 74
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Disease-free survival at 2 and 5 years after study completion
measure: Safety of arsenic trioxide following cytarabine and anthracycline immediately after study completion
Secondary outcomes:
measure: 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
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Comprehensive Cancer Center at University of Alabama at Birmingham
state: Alabama
city: Gainesville
country: United States
facility: University of Florida Shands Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Blood and Marrow Transplant Group of Georgia
state: Georgia
city: Baltimore
country: United States
facility: Greenebaum Cancer Center at University of Maryland Medical Center
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Omaha
country: United States
facility: UNMC Eppley Cancer Center at the University of Nebraska Medical Center
state: Nebraska
city: Pittsburgh
country: United States
facility: Hillman Cancer Center at University of Pittsburgh Cancer Institute
state: Pennsylvania
Study officials:
affiliation: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
name: Steven D. Gore, MD
role: STUDY_CHAIR
References: