Clinical Trial: Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Phase III Study for Patients With Newly Diagnosed Acute Promyelocytic Leukemia (APL) Using Arsenic Trioxide and All-trans Retinoic Acid

Brief Summary: This phase III trial studies tretinoin and arsenic trioxide in treating patients with newly diagnosed acute promyelocytic leukemia. Standard treatment for acute promyelocytic leukemia involves high doses of a common class of chemotherapy drugs called anthracyclines, which are known to cause long-term side effects, especially to the heart. Tretinoin may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Arsenic trioxide may stop the growth of cancer cells by either killing the cells, by stopping them from dividing, or by stopping them from spreading. Completely removing or reducing the amount of anthracycline chemotherapy and giving tretinoin together with arsenic trioxide may be an effective treatment for acute promyelocytic leukemia and may reduce some of the long-term side effects.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To eliminate exposure to conventional chemotherapy (including anthracyclines), for patients with standard risk acute promyelocytic leukemia (APL), through use of arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) (tretinoin) based therapy while achieving an event free survival (EFS) that is not inferior compared to historical controls.

II. To significantly reduce exposure to conventional chemotherapy, and in particular, anthracycline exposure, for patients with high risk APL, through use of ATO and ATRA based therapy while achieving an event free survival that is not inferior compared to historical controls.

SECONDARY OBJECTIVES:

I. To analyze the clinical impact of FMS-like tyrosine kinase 3 (FLT3) mutations in pediatric APL.

II. To correlate clinical outcomes with the kinetics of reduction in promyelocytic leukemia (PML)/retinoic acid receptor alpha (RARalpha) transcript level by quantitative reverse transcription-polymerase chain reaction (RT-PCR) (RQ-PCR) in bone marrow and peripheral blood samples from diagnosis to time points during therapy.

III. To monitor incidence of coagulopathy complications, utilizing standardized conventional supportive care, and correlate with a battery of coagulation testing.

IV. To evaluate the neurocognitive outcomes of patients treated on this protocol using patient-completed, performance-based measures of neuropsychological functioning and parent questionnaire report.

OUTLINE:

INDUCTION THERAPY: Patients with stand
Sponsor: Children's Oncology Group

Current Primary Outcome:

  • EFS in high risk (HR) APL patients [ Time Frame: 3 years ]
    EFS is defined as the time from on study to failure to achieve hematological CR prior to start of consolidation, persistence of molecular positive disease after MRD positive consolidation course, relapse (molecular, morphologic or extramedullary), or death. Will be compared against a fixed EFS of 71.1% at 36 months, which was observed for patients with HR APL treated on AIDA 0493. The Kaplan-Meier method will be used to estimate 3 year EFS along with 90% log-minus-log transformed confidence limits.
  • Event-free survival (EFS) in standard risk (SR) APL patients [ Time Frame: 2 years ]
    EFS is defined as the time from on study to failure to achieve hematological CR prior to start of consolidation, persistence of molecular positive disease after MRD positive consolidation course, relapse (molecular, morphologic or extramedullary), or death. EFS for patients with SR APL on will be compared against a fixed EFS of 91.3% at 24 months, which was observed for SR APL patients treated on AIDA 0493. The Kaplan-Meier method will be used to estimate 2 year EFS along with 90% log-minus-log transformed confidence limits.


Original Primary Outcome:

  • Event-free survival (EFS) in standard risk (SR) APL patients [ Time Frame: 2 years ]
    EFS is defined as the time from on study to failure to achieve hematological CR prior to start of consolidation, persistence of molecular positive disease after MRD positive consolidation course, relapse (molecular, morphologic or extramedullary), or death. EFS for patients with SR APL on will be compared against a fixed EFS of 91.3% at 24 months, which was observed for SR APL patients treated on AIDA 0493. The Kaplan-Meier method will be used to estimate 2 year EFS along with 90% log-minus-log transformed confidence limits.
  • EFS in high risk (HR) APL patients [ Time Frame: 3 years ]
    EFS is defined as the time from on study to failure to achieve hematological CR prior to start of consolidation, persistence of molecular positive disease after MRD positive consolidation course, relapse (molecular, morphologic or extramedullary), or death. Will be compared against a fixed EFS of 71.1% at 36 months, which was observed for patients with HR APL treated on AIDA 0493. The Kaplan-Meier method will be used to estimate 3 year EFS along with 90% log-minus-log transformed confidence limits.


Current Secondary Outcome:

Original Secondary Outcome:

Information By: Children's Oncology Group

Dates:
Date Received: January 13, 2015
Date Started: June 2015
Date Completion:
Last Updated: July 8, 2016
Last Verified: July 2016