Ivosidenib as Maintenance Therapy after Donor Stem Cell Transplant for the Treatment of IDH1-Mutated Acute Myeloid Leukemia

Inclusion Criteria

• PRIOR TO TRANSPLANTATION: 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
• PRIOR TO TRANSPLANTATION: Between the ages of 18 and 75 years
• PRIOR TO TRANSPLANTATION: Will undergo allogeneic hematopoietic stem cell transplantation (HCT) 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
• PRIOR TO TRANSPLANTATION: Karnofsky performance status >= 50
• PRIOR TO TRANSPLANTATION: Absolute neutrophil count >= 1000/uL without growth factor support (e.g. granulocyte colony-stimulating factor [GCSF]) in the previous 7 days
• PRIOR TO TRANSPLANTATION: Platelet count >= 50,000/uL without transfusional support in the previous 7 days
• PRIOR TO TRANSPLANTATION: Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) < 3 x institutional upper limit of normal (ULN)
• PRIOR TO TRANSPLANTATION: Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 3 x institutional upper limit of normal (ULN)
• PRIOR TO TRANSPLANTATION: Alkaline phosphatase < 3 x institutional upper limit of normal (ULN)
• PRIOR TO TRANSPLANTATION: Direct bilirubin < 2.0 mg/dL
• PRIOR TO TRANSPLANTATION: Calculated creatinine clearance >= 40 mL/min (Cockcroft-Gault formula)
• PRIOR TO TRANSPLANTATION: Left ventricular ejection fraction (LVEF) must be equal to or greater than 40%, as measured by MUGA scan or echocardiogram
• PRIOR TO TRANSPLANTATION: Female patients of childbearing potential must have a negative pregnancy test
• PRIOR TO TRANSPLANTATION: The effects of ivosidenib on the developing human fetus are unknown. For this reason female participants of child-bearing potential and male participants must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during the entire study treatment period and through 90 days after the last dose of treatment
• PRIOR TO TRANSPLANTATION: Ability to understand and the willingness to sign a written informed consent document
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): The patient has continued willingness and interest in participating in the study
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): There is no systemic infection requiring intravenous (IV) antibiotic therapy within 7 days preceding the first dose of study drug, or other severe infection
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): Chimerism studies reveal that >= 90% of blood or bone marrow cells, or of the CD33 expressing fraction, are of donor origin
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): There is no acute graft versus host disease (GVHD), requiring an equivalent dose of >= 0.5mg/kg/day of prednisone within one week of starting ivosidenib/placebo, or have escalation of systemic immunosuppression in terms of increase of corticosteroids or addition of new agent/modality within two weeks of starting ivosidenib/placebo
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): For prophylaxis for GVHD, agents that are permitted for administration on study: * Tacrolimus * Cyclosporine * Sirolimus * Cyclophosphamide * Mycophenolate Mofetil * Methotrexate * Anti-thymocyte globulin (ATG) * Ruxolitinib * Vedolizumab As standards of care may change, any other prophylactic agents used should be discussed with the principal investigator (PI). Investigational agents, defined as not approved for any indication, are forbidden unless the participant comes off study. * Agents used to treat GVHD that are permitted for administration on study: ** Any agent used in prophylaxis may be continued (see list above) ** Ruxolitinib ** Etanercept ** ATG ** Belumosudil ** Axatilimab ** Rituximab ** Fecal microbiota transplantation ** Alpha1-Antitrypsin ** Pregnyl ** Extracorporeal photopheresis (ECP) As standards of care may change, any other treatment agents used should be discussed with the PI. Investigational agents, defined as not approved for any indication, are forbidden unless the participant comes off study.
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): There is no evidence of relapsed/recurrent/residual disease
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): ANC >= 1000/uL
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): Platelets >= 50,000/uL
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): Direct bilirubin level < 2.0 mg/dL
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): AST (SGOT) < 3 x institutional upper limit of normal (ULN)
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): ALT (SGPT) < 3 x institutional upper limit of normal (ULN)
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): Alkaline phosphatase < 3 x institutional upper limit of normal (ULN)
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): No presence of congestive heart failure, defined by New York Heart Association (NHYA) criteria as class 3 or 4
• POST-TRANSPLANTATION PRE-TREATMENT (CYCLE 1, DAY 1): Calculated creatinine clearance >= 40 mL/min (Cockcroft-Gault formula)

Exclusion Criteria

• PRIOR TO TRANSPLANTATION: Prior allogeneic hematopoietic stem cell transplants
• PRIOR TO TRANSPLANTATION: Morphologically relapsed or refractory disease, as assessed by bone marrow aspirate and biopsy performed within 42 days prior to study entry
• PRIOR TO TRANSPLANTATION: 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 * The only prior malignancy was cervical cancer in situ and/or basal cell or squamous cell carcinoma of the skin
• PRIOR TO TRANSPLANTATION: Known diagnosis of active hepatitis B or hepatitis C
• PRIOR TO TRANSPLANTATION: Current or history of congestive heart failure New York Heart Association (NHYA) class 3 or 4, or any history of documented diastolic or systolic dysfunction (LVEF < 40%, as measured by MUGA scan or echocardiogram)
• PRIOR TO TRANSPLANTATION: Current or history of ventricular or life-threatening arrhythmias or diagnosis of long-QT syndrome
• PRIOR TO TRANSPLANTATION: Corrected QT (QTc) interval (i.e., Friderica's correction [QTcF]) >= 450 ms or other factors that increase the risk of QT prolongation or arrhythmic events (e.g., heart failure, hypokalemia, family history of long QT interval syndrome) at screening
• PRIOR TO TRANSPLANTATION: Uncontrolled intercurrent illness that would limit compliance with study requirements