Clinical Trial: Alvocidib, Cytarabine, and Mitoxantrone Hydrochloride or Cytarabine and Daunorubicin Hydrochloride in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

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

Official Title: Randomized Phase II Trial of Timed Sequential Therapy (TST) With Alvocidib (Flavopiridol), Ara-C and Mitoxantrone (FLAM) vs. "7+3" for Adults Age 70 and Under With Newly Diagnosed Acute Myel

Brief Summary: This randomized phase II trial is studying how alvocidib, cytarabine, and mitoxantrone hydrochloride work compared to cytarabine and daunorubicin hydrochloride in treating patients with newly diagnosed acute myeloid leukemia. Alvocidib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cytarabine, mitoxantrone hydrochloride, and daunorubicin hydrochloride work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. It is not yet known whether giving alvocidib, cytarabine, and mitoxantrone hydrochloride is more effective than giving cytarabine and daunorubicin hydrochloride in treating patients with acute myeloid leukemia.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To compare the rate of complete remission (CR) after 1 course of induction therapy with the timed-sequential combination of alvocidib (flavopiridol), cytarabine (cytosine arabinoside [ara-C]), and mitoxantrone hydrochloride (FLAM) vs traditional "7+3" cytarabine and daunorubicin hydrochloride (ara-C + Daunorubicin) for adults (age 18 to 70) with newly diagnosed, previously untreated, intermediate-risk or poor-risk acute myelogenous leukemia (AML).

SECONDARY OBJECTIVES:

I. To evaluate and compare the toxicities of FLAM vs 7+3. II. To compare the 2-year disease-free survival (DFS) and overall survival (OS) in response to FLAM vs 7+3.

III. To detect and compare the presence of minimal-residual disease (MRD) remaining after FLAM vs 7+3.

IV. To determine the expression of ABC transport proteins multidrug resistance 1 (MDR1, ABCB1) and breast cancer resistance protein (BCRP, ABCG2) on AML blasts pretreatment and correlate the expressions of one or both proteins with CR and DFS in response to FLAM vs 7+3.

OUTLINE: This is a multicenter study. Patients are stratified according to risk features: age (< 50 vs >= 50), secondary AML (pre-existing myelodysplatic syndrome [MDS], myeloproliferative diseases [MPD], treatment-related [t]-AML, or severe multi-lineage dysplasia) and/or known adverse cytogenetics, and hyperleukocytosis (white blood cells [WBC] >= 50,000/mm^3). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive alvocidib intravenously (IV) over 1 hour on days 1-3, cytarabine IV over 72 hours on days 6-8, and mitoxantr
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome: Complete response rate [ Time Frame: Up to 5 years ]

The final analysis will be by Fisher's exact test.


Original Primary Outcome: Complete response after one course of induction therapy (FLAM vs 7+3)

Current Secondary Outcome:

  • Incidence of toxicities, characterized as percentages by treatment and grade [ Time Frame: Up to 14 days after completion of study treatment ]
    The descriptions and grading scales found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 will be utilized for AE reporting.
  • Disease-free survival [ Time Frame: Time from randomization until death from any cause or relapse or recurrence, assessed up to 5 years ]
    Probabilities will be estimated with the Kaplan-Meier estimate. Survival estimates at two years will be estimated.
  • Overall survival [ Time Frame: From time of enrollment until time of death, assessed up to 5 years ]
    Probabilities will be estimated with the Kaplan-Meier estimate. Survival estimates at two years will be estimated.
  • Progression-free survival [ Time Frame: Time from study entry to the first date that recurrent or progressive disease is objectively documented, or death from any cause occurs, assessed up to 5 years ]
    Probabilities will be estimated with the Kaplan-Meier estimate. Survival estimates at two years will be estimated.
  • Proportion of patients with minimal residual disease [ Time Frame: Up to 5 years ]
    Comparisons of the treatments with respect to MRD will be based on the proportion of patients with MRD at each time point (e.g., day 14, recovery from induction but before beginning course 2, etc.).


Original Secondary Outcome:

  • Toxicity of FLAM vs 7+3
  • DFS and OS to FLAM vs 7+3 at 2 years
  • MRD after FLAM vs 7+3
  • Correlation between MDR with CR and DFS


Information By: National Cancer Institute (NCI)

Dates:
Date Received: May 6, 2011
Date Started: April 2011
Date Completion:
Last Updated: October 10, 2014
Last Verified: January 2014