Clinical Trial: Clofarabine or Daunorubicin Hydrochloride and Cytarabine Followed By Decitabine or Observation in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

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

Official Title: Phase III Randomized Trial of Clofarabine as Induction and Post-Remission Therapy vs. Standard Daunorubicin &Amp; Cytarabine Induction and Intermediate Dose Cytarabine Post-Remission Therapy, Foll

Brief Summary: This randomized phase III trial studies clofarabine to see how well it works compared with daunorubicin hydrochloride and cytarabine when followed by decitabine or observation in treating older patients with newly diagnosed acute myeloid leukemia. Drugs used in chemotherapy, such as clofarabine, daunorubicin hydrochloride, cytarabine, and decitabine, 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. It is not yet known which chemotherapy regimen is more effective in treating acute myeloid leukemia.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To evaluate the effect of clofarabine induction and consolidation therapy on overall survival in comparison with standard therapy (daunorubicin [daunorubicin hydrochloride] & cytarabine) in newly-diagnosed acute myeloid leukemia (AML) patients age >= 60 years.

SECONDARY OBJECTIVES:

I. To evaluate complete remission (CR) rates, duration of remission, and toxicity/treatment-related mortality of clofarabine in comparison with standard therapy (daunorubicin & cytarabine) in newly-diagnosed AML patients age >= 60 years.

II. To evaluate the feasibility of consolidation with reduced-intensity conditioning and allogeneic hematopoietic stem cell transplantation from human leukocyte antigen (HLA)-identical donors in patients who achieve a response to induction therapy, including the incidence of successful engraftment, acute and chronic graft-versus-host disease, transplant-related mortality, and its impact on overall survival in comparison to patients receiving chemotherapy.

III. To evaluate the duration of remission and disease-free survival of patients in complete remission following completion of consolidation therapy who are subsequently randomized to receive scheduled low-dose decitabine maintenance in comparison with observation.

IV. To perform expression and methylation profiling on all patients receiving decitabine and to correlate their integrated epigenetic signatures with response to decitabine.

V. To examine the epigenetic profiles of remission marrow in patients randomized to observation vs. decitabine to determine whether epigenetic sig
Sponsor: Eastern Cooperative Oncology Group

Current Primary Outcome: Overall survival [ Time Frame: Time between randomization and death from any cause, assessed up to 5 years ]

Due to the potential confounding by maintenance therapy on the induction comparison, a weighted analysis (weighted Cox regression) will be used for the primary analysis.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Mortality rate [ Time Frame: 30 days ]
  • Induction complete response rates [ Time Frame: Up to 5 years ]
    The induction response (CR + CRi) rates will be compared between the clofarabine arm and the standard treatment arm. At the end of the study, the 95% confidence interval on the difference in the CR + CRi rates (CR + CRi rate of standard treatment - CR + CRi rate of clofarabine) will be computed based on the normal approximation to the difference of two independent binomial proportions.
  • Disease-free survival (DFS) [ Time Frame: Time from the second randomization to relapse or death without relapse, assessed up to 5 years ]
    The primary analysis of DFS will use a one-sided log rank test stratified on the induction therapy and on patient age and cytogenetics to determine the effect of decitabine on DFS as a maintenance therapy in comparison with observation.
  • Overall survival [ Time Frame: Up to 5 years ]
    To evaluate the impact of consolidation with non-ablative conditioning and allogeneic hematopoietic stem cell transplantation with an HLA-identical sibling on overall survival in patients who achieve a 'morphologic leukemia-free state, a one-sided log rank test stratified on age, therapy-related AML, the presence of AHD at the time of diagnosis of AML, and the induction therapy they received will be used.
  • Epidemiological factors, measured using the Acute Leukemia Epidemiology and Survival in ECOG (ALESE) questionnaire [ Time Frame: Baseline ]
    The proportions of obese patients and patients who had benzene exposure, ever smoked in their lifetime, took aspirin regularly, took acetaminophen regularly, ever lived in rural/farm environments, or had other exposures or lifestyle factors will be calculated separately, along with their 95% confidence intervals.
  • Change in the Functional Assessment of Cancer Therapy (FACT)-Leukemia-specific (Leu) Trial Outcome Index (TOI) score [ Time Frame: Baseline to 30 days after beginning induction therapy ]
    Descriptive statistics will be provided and Cronbach's alpha will be calculated at each time point to assess reliability. Repeated measures analysis techniques will also be utilized to examine the treatment effect and time effect on FACT-Leu TOI score. For patients randomized to the induction treatments, the longitudinal scores collected from time of randomization, two weeks after beginning induction therapy (at the time of nadir), and at 28-30 days after beginning induction therapy, will be analyzed according to the methods described in Schluchter and Schluchter, Greene and Beck.
  • Change in the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score [ Time Frame: Baseline to 30 days after beginning induction therapy ]
    Descriptive statistics will be provided and Cronbach's alpha will be calculated at each time point to assess reliability. Repeated measures analysis techniques will also be utilized to examine the treatment effect and time effect on FACIT Fatigue score. For patients randomized to the induction treatments, the longitudinal scores collected from time of randomization, two weeks after beginning induction therapy (at the time of nadir), and at 28-30 days after beginning induction therapy, will be analyzed according to the methods described in Schluchter and Schluchter, Greene and Beck.


Original Secondary Outcome: Same as current

Information By: Eastern Cooperative Oncology Group

Dates:
Date Received: March 11, 2014
Date Started: December 2010
Date Completion:
Last Updated: September 16, 2014
Last Verified: September 2014