This is a Phase 2 study of the study drug, ivosidenib (a mutant IDH1 inhibitor), compared to placebo, given to patients with IDH1-mutant acute myeloid leukemia (AML) after hematopoietic stem cell transplantation (HCT).
This is a prospective, placebo-controlled, randomized, single-blinded, multi-center, phase II study of the mutant IDH1 inhibitor, ivosidenib, compared to placebo in participants with AML after HCT. This study is examining whether or not ivosidenib is beneficial as an agent to prevent the relapse of IDH1-mutated acute myeloid leukemia after hematopoietic stem cell transplantation. The U.S. Food and Drug Administration (FDA) has not approved ivosidenib for this indication following HCT but it has been approved for other uses. The research study procedures include screening for eligibility and study treatment including evaluations and follow-up. The HCT and any standard treatment before and after the HCT is standard of care. The estimated length of participation in the study is 3.5 years from screening to the end of planned follow-up, including up to 24 months of study treatment. After the 24-month period, participants are followed for up to 12 additional months. It is expected that about 75 people will take part in this research study. Servier, a pharmaceutical company, is supporting this research study by providing ivosidenib/placebo and funding for research activities.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
75
Ivosidenib tablets are supplied as 50 mg, 200 mg, and 250 mg strengths, to be taken orally.
Placebo tablets are taken orally.
Massachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGDana Farber Cancer Institute
Boston, Massachusetts, United States
NOT_YET_RECRUITINGRelapse-Free Survival (RFS)
Relapse-Free Survival is defined as the time from randomization following transplant to disease relapse or death due to any cause, whichever occurs first. Participants alive without relapse are censored at the date of last seen alive. The primary analysis will be performed using the Kaplan-Meier method with log-rank test.
Time frame: Time of randomization to 24 months post-randomization, death, or disease relapse whichever occurs first.
Overall Survival (OS)
Overall Survival is defined as the time from stem cell transplant (HCT) to the date of death due to any cause. Participants who are alive at the analysis / cutoff date will be censored at the last contact date. Baseline characteristics will be reported descriptively and compared using Fisher's exact test, χ2 test or Wilcoxon rank-sum test, as appropriate. The Kaplan-Meier method will be used to estimate OS; Multivariable Cox regression analysis will be used for OS analysis.
Time frame: Up to 39 months (Day of HCT (Day -90 to Day -45) through 24 months of treatment period and 12 months of follow-up)
Incidence of treatment related adverse events (TRAE)
TRAEs will be graded and categorized using the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5. Baseline characteristics will be reported descriptively and compared using Fisher's exact test, χ2 test or Wilcoxon rank-sum test, as appropriate.
Time frame: Up to 25 months (Day 1 of study drug treatment for up to 24 months of treatment plus 30 days post final dose)
Cumulative incidence of acute and chronic Graft vs. Host Disease (GVHD)
Chronic GVHD will be assessed as per the National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease. Cumulative incidence of acute and chronic GVHD (grade II-IV acute GVHD, grade III-IV acute GVHD, chronic GVHD, steroid-requiring chronic GVHD) will be estimated in the context of a competing risks framework. Gray test and Gray regression analysis will be used for comparison of cumulative incidence of GVHD.
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Time frame: Up to 36 months (Start of study treatment for 24 months, plus 12 months of follow-up)
Measurable Residual Risease (MRD)
MRD will be assessed by Next Generation Sequencing (NGS) testing at screening before stem cell transplant, post-transplant before initiation of study treatment, and at the start of study treatment cycles 6 and 12.
Time frame: Pre-transplant screening (up to Day -132) through 12 months of study treatment period, for up to 16.5 months.
Cumulative incidence rate of relapse of acute myeloid leukemia (AML)
Disease assessment (relapse) will be based on modified IWG criteria or other appropriate response criteria for the malignancy being studied. Cumulative incidence of relapse of AML will be estimated in the context of a competing risks framework using the Gray test and Fine and Gray regression analysis.
Time frame: From stem cell transplant through 12 months treatment period or relapse, whichever is first., up to 15 months.