Ziftomenib Maintenance Post Allo-HCT

NCT06440135 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 24-096
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

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

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (Dose Escalation)

  Defined as the highest dose level at which 1 or 0 of 6 patients experience a Dose Limiting Toxicity (DLT). Toxicities will be graded and documented according to NCI CTCAE version 5.0. A non-hematologic DLT is any grade 3 adverse event (AE) lasting \>72 hours or any grade greater than or equal to 4 AE that is at least possibly related to the study drug with exceptions. Any ≥ grade 2 non-hematologic toxicity that the participant finds intolerable or renders the participant unable to take 75% or more of the assigned doses (e.g. multiple dose interruptions) during the first cycle will be considered a DLT.

  28 days

Secondary Outcomes (11)

• Occurrence of ziftomenib-related toxicities

  Day 0 to last treatment dose, up to 336 days

• Incidence of acute Graft versus Host Disease (GVHD) during treatment

  Day 0 to end of treatment visit, up to 366 days (336 days of treatment + 30 days end of treatment)

• Incidence of chronic Graft versus Host Disease (GVHD) during treatment

  Day 0 to end of treatment visit, up to 366 days (336 days of treatment + 30 days end of treatment)

• Non-relapse mortality (NRM)

  Day 0 to end of treatment visit, up to 1086 days (336 days of treatment + 30 days end of treatment + 24 months follow-up))

• Leukemia-Free Survival (LFS)

  Day 0 to end of treatment visit, up to 1086 days (336 days of treatment + 30 days end of treatment + 24 months follow-up))

Study Arms (1)

Ziftomenib

EXPERIMENTAL

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

Drug: Ziftomenib

Interventions

Ziftomenib DRUG

Taken orally once per day

Also known as: KO-539

Ziftomenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Ohio State University Wexner Medical Center- James Cancer Hospital

Columbus, Ohio, 43210, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Zachariah DeFilipp, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zachariah DeFilipp, MD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 5, 2024
• First Posted: June 3, 2024
• Study Start: June 11, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: MGH - Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)