Clinical Trial: Tretinoin, Cytarabine, and Daunorubicin Hydrochloride With or Without Arsenic Trioxide Followed by Tretinoin With or Without Mercaptopurine and Methotrexate in Treating Patients With Acute Promyelocytic Leukemia

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase III Randomized Study of Concurrent Tretinoin and Chemotherapy With or Without Arsenic Trioxide (AS2O3) (NSC # 706363) as Initial Consolidation Therapy Followed by Maintenance Therapy With Interm

Brief Summary: This randomized phase III trial is studying tretinoin and combination chemotherapy to see how well they work compared to tretinoin, combination chemotherapy, and arsenic trioxide in treating patients with acute promyelocytic leukemia that has not been treated previously. Drugs used in chemotherapy, such as daunorubicin, cytarabine, mercaptopurine, methotrexate, and arsenic trioxide, work in different ways to stop cancer cells from dividing so they stop growing or die. Tretinoin may help leukemia cells develop into normal white blood cells. It is not yet known which regimen is more effective for acute promyelocytic leukemia.

Detailed Summary:

PRIMARY OBJECTIVES:

i. To compare the efficacy (event-free survival) and toxicities of two induction/consolidation therapies for patients with untreated APL: ATRA/ara-C/daunorubicin with or without arsenic trioxide (As2O3).

II. To evaluate the efficacy (disease-free survival) and toxicities of maintenance therapy with intermittent ATRA vs intermittent ATRA plus 6-MP/MTX for patients with APL who achieve a complete response.

III. To explore the relationship between CD56 expression at diagnosis and clinical outcomes.

IV. To evaluate the cardiac toxicity of intensive daunorubicin therapy, as given in this study, to pediatric patients.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (under 15 vs 15 to 60 vs over 60) for the induction phase. Patients are stratified according to age, as in the induction phase, and the consolidation arm (with vs without arsenic trioxide) for the consolidation phase. Patients under age 5 do not receive arsenic trioxide.

Induction: All patients receive oral tretinoin every 12 hours beginning on day 1 until complete response or for a maximum of 90 days. Patients also receive daunorubicin IV on days 3-6 and cytarabine IV continuously on days 3-9.

Consolidation: All patients achieving complete response (CR), or partial response (PR) after completion of tretinoin, proceed to consolidation within 2 weeks of achieving CR or PR, but not prior to 30 days from the start of induction. Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral tretinoin
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

  • Response rates [ Time Frame: Up to 10 years ]
  • Distributions of event-free survival [ Time Frame: Up to 10 years ]
  • Disease-free survival [ Time Frame: Time from the date of the maintenance randomization to relapse or death, assessed up to 10 years ]
  • Survival [ Time Frame: Up to 10 years ]
  • Toxicities for the various therapies graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [ Time Frame: Up to 30 days after last dose of study treatment ]


Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Cancer Institute (NCI)

Dates:
Date Received: November 1, 1999
Date Started: June 1999
Date Completion:
Last Updated: June 4, 2013
Last Verified: June 2013