Clinical Trial: Daunorubicin & Cytarabine +/- Zosuquidar inTreating Older Patients With Newly Diagnosed Acute Myeloid Leukemia or Refractory Anemia

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

Official Title: A Randomized, Placebo-Controlled, Double Blind, Trial of the Administration of the MDR Modulator, Zosuquidar Trihydrochloride (LY335979), During Conventional Induction and Post-Remission Therapy in Pa

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Zosuquidar trihydrochloride, a modulator of multidrug resistance (MDR), may help daunorubicin and cytarabine kill more cancer cells by making cancer cells more sensitive to the drugs. It is not yet known whether daunorubicin and cytarabine are more effective with or without zosuquidar trihydrochloride in treating acute myeloid leukemia or anemia.

PURPOSE: This randomized phase III trial is studying how well giving zosuquidar trihydrochloride together with daunorubicin and cytarabine works compared to daunorubicin and cytarabine alone in treating older patients with newly diagnosed acute myeloid leukemia or anemia that has not responded to previous treatment.


Detailed Summary:

OBJECTIVES:

  • Compare the overall survival and progression-free survival of elderly patients with newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts (RAEB) in transformation, or high-risk RAEB treated with daunorubicin and cytarabine with or without zosuquidar trihydrochloride.
  • Compare the complete remission rate of patients treated with these regimens.
  • Compare the toxicity of these regimens in these patients.
  • Compare the systemic exposure of daunorubicin and cytarabine in patients treated with zosuquidar trihydrochloride vs placebo.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (60-69 years vs 70 years and over), disease (refractory anemia with excess blasts [RAEB] vs RAEB in transformation or acute myeloid leukemia [AML]), and disease type (de novo vs secondary). Patients are randomized to 1 of 2 treatment arms.

  • Induction:

    • Arm I: Patients receive daunorubicin via intravenous (IV) infusion over 10-15 minutes and zosuquidar trihydrochloride IV over 6 hours on days 1-3. Patients also receive cytarabine IV continuously on days 1-7.
    • Arm II: Patients receive daunorubicin and cytarabine as in arm I. Patients also receive placebo IV over 6 hours on days 1-3.

Beginning on day 12, patients who achieve aplasia receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously (SC)
Sponsor: Eastern Cooperative Oncology Group

Current Primary Outcome: Overall Survival (OS) [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter ]

Time from randomization to death. Patients alive at last follow-up were censored.


Original Primary Outcome:

Current Secondary Outcome:

  • Progression-free Survival (PFS) [ Time Frame: Assessed every 3 months for 2 years, then every 6 months for 3 years, then annually thereafter ]
    Time from randomization to the earlier of disease progression or death. Patients alive and progression-free at last follow-up were censored.
  • Response [ Time Frame: Assessed at the end of induction ]
    Number of eligible participants in each response category. Categories, based on peripheral blood counts and bone marrow aspirate and biopsy, include complete remission (CR), partial remission (PR), morphologic complete remission (MCR), and relapse.


Original Secondary Outcome:

Information By: Eastern Cooperative Oncology Group

Dates:
Date Received: October 3, 2002
Date Started: July 2002
Date Completion:
Last Updated: June 1, 2015
Last Verified: June 2015