Ziftomenib treatment after blood cancer transplant

Inclusion Criteria:

* 18 years or older.
* Pathologically confirmed diagnosis of acute myeloid leukemia (AML).
* Complete remission (CR) or complete remission with incomplete count recovery (CRi) at screening.

  * Complete remission (CR):

    * no circulating blasts in peripheral blood and \<5% blasts in bone marrow
    * no extramedullary disease
    * platelet count ≥100 x 10(9)/L and/or absolute neutrophil count ≥1000/µL
  * Complete remission with incomplete count recovery (CRi):

    * no circulating blasts in peripheral blood and \<5% blasts in bone marrow
    * no extramedullary disease
    * platelet count \<100 x 10(9)/L and/or absolute neutrophil count \<1000/µL
* Presence of at least one of the following molecular mutations:

  * KMT2A rearrangement

    * Eligibility and enrollment will be based on local mutational testing.
    * The presence of a KMT2A rearrangement (excluding partial tandem duplication \[PTD\]) at the time of initial diagnosis or any other time thereafter is sufficient.
    * Participants may receive additional treatment for AML between consent and transplant.
  * NPM1 mutation

    * Eligibility and enrollment will be based on local mutational testing.
    * For participants being transplanted in CR1, the presence of a NPM1 mutation at screening is necessary for the purposes of eligibility.
    * For participants being transplanted in greater than or equal to CR2, the presence of a NPM1 mutation at the time of consent is not necessary for eligibility and its presence at the time of initial diagnosis or any other time thereafter is sufficient.
    * Participants may receive additional treatment for AML between consent and transplant.
* Treatment with a menin inhibitor prior to transplant is permitted. However, patients who experienced AML relapse or progression while being treated with a menin inhibitor prior to transplant are ineligible.
* Will undergo first allogeneic HCT for their malignancy.
* Transplantation will be performed with the use of conventional myeloablative (MAC) or reduced intensity conditioning (RIC).
* HCT Donor will be one of the following:

  * 5/6 or 6/6 (HLA-A, B, DR) matched related donor
  * 7/8 or 8/8 (HLA-A, B, DR, C) matched unrelated donor. Matching in the unrelated setting must be at the allele level.
  * Haploidentical related donor, defined as ≥ 3/6 (HLA-A, B, DR) matched
  * ≥ 4/6 (HLA-A, B, DR) umbilical cord blood (UCB). Matching in the UCB setting is at the antigen level. Recipients may receive either one or two UCB units. In the case of 2 UCB units, both units must have been at least 4/6 matched with the recipient.
* Any non-investigational GVHD prophylaxis regimen is allowed.
* Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
* Participants must have normal organ and function as defined below:

  * AST (SGOT), ALT (SGPT) and Alkaline phosphatase \< 3x institutional upper limit of normal (ULN)
  * Total bilirubin \< 1.5 x institutional ULN (with the exception of subjects with a history of Gilbert's syndrome, for which the total bilirubin must be \< 5 x ULN)
  * Calculated creatinine clearance ≥ 30 mL/min (Cockcroft-Gault formula)
* LVEF must be ≥50%, as measured by MUGA scan or echocardiogram.
* Female patients of childbearing potential must have a negative pregnancy test, as measured by serum or urine testing.
* The effects of ziftomenib on the developing human fetus are unknown. For this reason women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) during the entire study treatment period and through 6 months after the last dose of treatment.
* Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

* History of other malignancy(ies) unless

  * the participant has been disease-free for at least 2 years and is deemed by the investigator to be at low risk of recurrence of that malignancy, or
  * the cancer has been deemed indolent with no progression over the last 2 years, and deemed by the investigator to be at low risk for further progression during the course of study and follow-up
  * the only prior malignancy was cervical cancer in situ and/or basal cell or squamous cell carcinoma of the skin
* Known diagnosis of active hepatitis B or hepatitis C
* 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 \< 50%, as measured by multigated acquisition (MUGA) scan or echocardiogram)
* Current or history of ventricular or life-threatening arrhythmias or diagnosis of long-QT syndrome
* Systemic uncontrolled infection
* Known dysphagia, short-gut syndrome, gastroparesis, or other condition(s) that limits the ingestion or gastrointestinal absorption of drugs administered orally
* Uncontrolled hypertension (systolic blood pressure \[BP\] \> 180 mmHg or diastolic BP \> 100 mmHg)
* QTc interval (i.e., Friderica's correction \[QTcF\]) ≥ 480 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
* Uncontrolled intercurrent illness that would limit compliance with study requirements.
* Persons who are pregnant or lactating.