Recruiting
Phase 1

Ziftomenib

Sponsor:

Massachusetts General Hospital

Code:

NCT06440135

Conditions

Acute Myeloid Leukemia

Acute Myeloid Leukemia in Remission

NPM1 Mutation

KMT2A Rearrangement

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Ziftomenib

Study Details

Brief summary:

The purpose of this study is to test the safety, effects, and recommended dose of an investigational drug, ziftomenib, in addition to the standard treatment on blood cancer with Allogeneic Hematopoietic Cell Transplantation (allo-HCT). This study plans to learn more about ziftomenib, which targets and inhibits negative interactions within cancer cells related to AML, when given after allo-HCT, to determine if it improves outcomes following allo-HCT.

The name of the study drug involved in this study is:

• Ziftomenib

Conditions

Acute Myeloid Leukemia

Acute Myeloid Leukemia in Remission

NPM1 Mutation

KMT2A Rearrangement

Study ID

NCT06440135

Start date

Jun 11, 2024

Status verified date

Oct, 2026

Completion date

Apr 1, 2029

Anticipated

Primary completion date

Apr 1, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

22 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Ziftomenib

Participants will begin treatment 30 to 90 days after allo-HCT and only after disease remission is confirmed, and treatment will continue for up to 12 months. All participants will receive ziftomenib. Participants will undergo allo-HCT as a part of their standard care.

Participants will undergo the following procedures:

  • Screening
  • Allo-HCT (standard care), including pre and post-treatment as a part of standard care
  • 30 - 90 days after allo-HCT, participants will take the study drug orally once per day for up to 12 28-day cycles
  • End of treatment visit
  • Follow-up data will be collected every 3 months for 24 months from the start of treatment

Interventions

Ziftomenib

Taken orally once per day

Primary outcome measure

  • Maximum Tolerated Dose (Dose Escalation) [ Time Frame: 28 days ]

Central Contacts and Locations

Central contacts

Zachariah DeFilipp, MD

(617) 726-5765zdefilipp@mgh.harvard.edu

Locations

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Contacts

Zachariah DeFilipp, MD

(617) 726-5765zdefilipp@mgh.harvard.edu

Ohio State University Wexner Medical Center- James Cancer Hospital

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Hannah Choe, MD

614-293-7526Hannah.Choe@osumc.edu

Principal Investigator:

Hannah Choe, MD

More Information

Sponsor

Massachusetts General Hospital

Last update posted

Oct 6, 2026

Last verified

Oct, 2026

Keywords

  • Acute Myeloid Leukemia
  • Allogeneic hematopoietic cell transplantation (HCT)
  • Allo-HCT
  • NPM1 Mutation
  • KMT2A Rearrangement

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-23. This information was provided to ClinicalTrials.gov by Massachusetts General Hospital on 2026-10-06. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.