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Ivosidenib as Post-HSCT Maintenance for AML

ConditionsIDH1 MutationAcute Myeloid Leukemia (AML)Hematopoietic Stem Cell Transplant (HSCT)
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-75
SponsorMassachusetts General Hospital

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Pathologically confirmed diagnosis of IDH1(R132)-mutant acute myeloid leukemia (AML). IDH1 mutations could have been detected by any mutational technique at any prior point including at diagnosis or remission.

Between the ages of 18 and 75 years

Will undergo allogeneic hematopoietic stem cell transplantation (HSCT) for their malignancy. Conditioning may be either conventional myeloablative (MAC) or reduced intensity conditioning (RIC). There will be no restrictions on type of graft source.

ECOG performance status ≤ 2

Disqualifiers

Prior allogeneic hematopoietic stem cell transplants.

Morphologically relapsed or refractory disease, as assessed by bone marrow aspirate and biopsy performed within 42 days prior to study entry

History of other malignancy(ies) unless

the participant has been disease-free for at least 5 years and is deemed by the investigator to be at low risk of recurrence of that malignancy, or

Trial design

Design model

Parallel

Treatments tested in this trial

  • Ivosidenib

    Drug

    Ivosidenib tablets are supplied as 50 mg, 200 mg, and 250 mg strengths, to be taken orally.

  • Placebo

    Drug

    Placebo tablets are taken orally.

Treatment groups

75 Participants
are divided into 2 treatment groups
Group A: IvosidenibExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention

Trial outcomes

Primary outcomes

1

Relapse-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.

Secondary outcomes

1

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)
2

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)
3

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.

Time frame
Up to 36 months (Start of study treatment for 24 months, plus 12 months of follow-up)
4

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.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Massachusetts General Hospital

Lead sponsor

Servier

Collaborator

Source ClinicalTrials.gov
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