Study Design: This is a two-stage Phase II trial investigating the efficacy of Clofarabine, Cyclophosphamide and Etoposide in acute leukemia patients with detectable minimal residual disease (MRD) prior to allo-HCT. The primary objective is to determine the impact of the study treatment in eliminating the presence of minimal residual disease without causing a significant delay of allo-HCT due to treatment related toxicity. The intent of this study is to allow patients to proceed to transplant (independent of this study) within 42 days of Day 1 of Clofarabine based therapy.
Patients will be stratified at the time of enrollment based on diagnosis (ALL versus AML). Based on this two-stage optimal design, a maximum of 49 patients with ALL and a maximum of 49 patients with AML will be needed. For each disease cohort, 21 patients will be enrolled in stage 1. If at the end of stage 1, the criteria is met for activating stage 2 (based on success of clearing MRD, proceeding to transplant within 42 days and without excessive toxicity) for one or both groups, stage 2 will be activated with an additional 28 patients enrolled.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Days 1-5: Clofarabine 30 mg/m\^2 for 0-30 years of age or 20 mg/m\^2 for \> 30 years of age intravenously (IV) over 2 hours
Days 1-5: Etoposide 100mg/m\^2 IV over 2 hours
Days 1-5: Cyclophosphamide 300 mg/m\^2 as a 30-60 minute infusion
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States
Number of Patients Unable to Proceed to Transplantation
The primary endpoint of this study will be to determine the impact of Clofarabine, Cyclophosphamide and Etoposide on the conversion to an minimal residual disease (MRD) negative state at day 30 (\<0.01% leukemic blasts by flow cytometry) or day 42 if day 30 marrow is un-evaluable due to hypocellularity per RECIST criteria as well as the ability of patients to reach allo-HCT without significant delay due to study treatment related toxicity. Unable to proceed to transplant by Day 42 will be considered unacceptable.
Time frame: Between Day 30 and Day 42
Rate of Pre-Transplant Chemotherapy-Induced Aplasia
defined as greater than 42 days after infusion of chemotherapy
Time frame: After Day 42
Rate of Infectious Complications
Time frame: Day 1 Through Day 30
Treatment-Related Mortality After Transplant
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Time frame: Day 100
Disease-Free Survival After Transplant
The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.
Time frame: 1 Year
Rate of Leukemic Relapse After Transplant
The return of disease after its apparent recovery/cessation.
Time frame: Day 100
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Between Days 28 and 42: infused independent of this study