Olutasidenib for the Treatment of Patients With IDH1 Mutated AML, MDS or CMML After Donor Hematopoietic Cell Transplant

Description

PRIMARY OBJECTIVE:

I. Evaluate the safety and tolerability of olutasidenib as maintenance therapy after allogeneic hematopoietic cell transplantation (HCT) in patients with IDH1-mutated acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myelomonocytic leukemia (CMML).

SECONDARY OBJECTIVES:

I. Assess overall survival (OS) and leukemia-free survival (LFS) at 1 and 2 years after first dose of olutasidenib.

II. Estimate cumulative incidence of relapse (CIR), non-relapse mortality (NRM), graft-versus-host disease (GVHD) free, relapse-free survival (GRFS) at 1 and 2 years after first dose of olutasidenib.

III. Rate and grading of acute GVHD of grades 2-4 and 3-4 at day 100 post allogeneic HCT.

IV. Incidence and grading of chronic GVHD of all grades at 1 and 2 years after first dose of olutasidenib.

EXPLORATORY OBJECTIVES:

I. Monitor disease status by multiparameter flow cytometry among a subset of patients with minimal residual disease (MRD)+ disease when starting olutasidenib.

II. Molecular monitoring of disease status by HopeSeq complete (at City of Hope [COH]) and equivalent next generation sequencing (NGS) assay at Cleveland Clinic.

III. Monitor immune reconstitution by flow cytometry during protocol therapy. IV. Mutant (m)IDH1 testing on peripheral blood samples with standard polymerase chain reaction (PCR).

V. Investigate IFN-ɣ signaling in immune cell subsets before and during maintenance therapy.

VI. Monitor mIDH1 variant allele fraction (VAF) by droplet digital PCR (ddPCR) beads, emulsion, amplification, magnetics (BEAM)ing technology on peripheral blood.

OUTLINE:

Starting 50-120 days after bone marrow transplant, patients receive olutasidenib orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection on study.

After completion of study treatment, patients are followed up at 30 days and then up to 2 years.