Clinical Trial: Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia

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

Official Title: Phase II Trial of Vosaroxin in Combination With Infusional Cytarabine in Patients With Untreated AML

Brief Summary: This phase II trial studies how well vosaroxin and cytarabine work in treating patients with untreated acute myeloid leukemia. Drugs used in chemotherapy, such as vosaroxin and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading.

Detailed Summary:

PRIMARY OBJECTIVES:

I. To assess the rate of complete remission (CR) after induction therapy with the combination of "7+V" (vosaroxin and standard dose infusional cytosine arabinoside [ara-C]) for patients with newly diagnosed, previously untreated acute myelogenous leukemia (AML).

SECONDARY OBJECTIVES:

I. Frequency of grade 3-5 adverse events related to administration of "7+V".

II. To evaluate for the presence of minimal residual disease (MRD) remaining after "7+V" induction and/or re-induction.

III. To determine the CR/CR with incomplete blood count recovery (CRi) rate after one and/or 2 cycles of "7+V" induction.

IV. To determine the time to neutrophil and platelet recovery following "7+V" induction.

V. To assess disease-free survival (DFS) at 1 year (yr) of patients achieving CR/CRi after "7+V" induction.

VI. To assess overall survival (OS) at 1 yr of all patients receiving protocol-defined therapy.

VII. To determine the correlation of hematopoietic stem cell transplant (HSCT) comorbidity index and Wheatley Index scores with disease response, DFS and OS.

TERTIARY OBJECTIVES:

  • I. To describe the mutational burden of this cohort of AML patients.
  • II. To correlate genomic aberration with response rate, DFS, and OS.
  • III. To
    Sponsor: Vanderbilt-Ingram Cancer Center

    Current Primary Outcome: Complete remission rate (CR) [ Time Frame: Up to 3 months ]

    A likelihood ratio, not a tail area probability (p-value), will be used to represent the strength of statistical evidence with respect to either a 40% or 60% true CR rate. It is assumed the complete remission rate of standard induction chemotherapy is 40% in the targeted population of this trial and that the use of vosaroxin in combination with cytarabine may increase this rate to 60%.


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Event-free survival [ Time Frame: The time from start of therapy to progression or death for any reason, assessed up to 1 year ]
      Survival distribution will be estimated using the method of Kaplan and Meier and comparison of the distribution among patient subgroups will be made using the logrank test. Multivariable models of response and survival estimates will be constructed using logistic and Cox (proportional hazards) regression.
    • Frequency of grade 3-5 adverse event related to Cytarabine and Vosaroxin (7+V) [ Time Frame: Up to day 3 months ]
      Events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Frequency and percentage of patients will be summarized for any adverse event by grade, attribution, organ class, and preferred term overall and by patient. Change in continuous laboratory data from just prior to therapy and by visit will be summarized by frequency of abnormal values. Linear and non-linear regression will be used to model changes over time, accounting for intra-patient correlation using mixed models or generalized estimating equation, as appropriate.
    • Leukemia-free survival (LFS or DFS) [ Time Frame: The time from complete remission to disease progression or death for any reason, assessed up to 1 year ]
      Survival distribution will be estimated using the method of Kaplan and Meier and comparison of the distribution among patient subgroups will be made using the logrank test. Multivariable models of response and survival estimates will be constructed using logistic and Cox (proportional hazards) regression. Time to response will be implemented as a time-dependent covariate in models assessing LFS.
    • Overall Survival [ Time Frame: The time from start of therapy to death for any reason, assessed up to 1 year ]
      Survival distribution will be estimated using the method of Kaplan and Meier and comparison of the distribution among patient subgroups will be made using the logrank test. Multivariable models of response and survival estimates will be constructed using logistic and Cox (proportional hazards) regression.
    • Minimal Residual Disease [ Time Frame: Up to 3 months ]
      Frequency of minimal residual disease (MRD) remaining after "7+V" induction and/or re-induction
    • Rate of Complete Remission / Complete Remission with Incomplete Count Recovery (CR/CRi) [ Time Frame: Up to 3 months ]
      Frequency of CR/CRi after "7+V" induction and/or re-induction


    Original Secondary Outcome: Same as current

    Information By: Vanderbilt-Ingram Cancer Center

    Dates:
    Date Received: January 14, 2016
    Date Started: March 2016
    Date Completion: July 2019
    Last Updated: April 5, 2017
    Last Verified: April 2017