Primary Outcomes

Description: Will be compared using log-rank tests. EFS curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model. The corresponding hazard ratio, 2- and 3-year EFS estimates will be assessed, and EFS medians along with their 95% confidence intervals for the two treatment arms.

Measure: EFS

Time: Time from induction response to the time of progressive-disease, secondary malignancy, or death, assessed up to 3 years

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Secondary Outcomes

Measure: DFS

Time: Time from achievement of CR to the time of relapse and/or death, assessed up to 10 years

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Description: Will be evaluated using Kaplan-Meier as well as Cox regression models.

Measure: OS

Time: Time from randomization to the time of death due to any cause, assessed up to 10 years

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Description: Will be summarized as the proportion of patients who achieve any type of response to induction therapy divided by the number of all evaluable patients registered to this trial and who received at least one dose of induction therapy. Corresponding 95% binomial confidence intervals will also be calculated.

Measure: Proportion of patients who achieve CR or any response to induction therapy

Time: Up to 10 years

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Description: Will be summarized as the proportion of patients who achieve any type of response to induction therapy divided by the number of all evaluable patients registered to this trial and who received at least one dose of induction therapy. Corresponding 95% binomial confidence intervals will also be calculated.

Measure: Overall induction response rates

Time: Up to 10 years

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Description: The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. In addition, all adverse event data that is graded as 3, 4, or 5 will be reviewed and classified as either "unrelated" or "unlikely to be related" to study treatment in the event of an actual relationship developing. The incidence of severe (grade 3+) adverse events or toxicities will be described for each treatment arm, but will also be compared between the arms. Fisher's exact tests will be used to quantitatively compare the incidence of severe as well as specific toxicities of interest between the treatment arms and we will graphically assess differences in maximum grades observed for toxicities between the arms. Tolerability of the treatment arms will be assessed through assessing the number of patients who required dose modifications and/or dose delays.

Measure: Incidence of adverse events as assessed by Common Terminology Criteria for Adverse Events version 4.0

Time: Up to 10 years

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Description: Will be assessed within each of the treatment arms and differences explores in these measures between the arms.

Measure: Proportion of patients who go off treatment due to adverse reactions

Time: Up to 10 years

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Description: Will be assessed within each of the treatment arms and differences explores in these measures between the arms.

Measure: Proportion of patients who refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial

Time: Up to 10 years

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