RECRUITING

Ziftomenib Maintenance Post Allo-HCT

Conditions

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

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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

Official Title

An Open Label Phase I Study of Ziftomenib As Maintenance Therapy Following Allogeneic Hematopoietic Cell Transplantation

Quick Facts

Study Start:2024-06-06

Study Completion:2027-09-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06440135

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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.

Inclusion Criteria

Exclusion 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.

* 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.

Contacts and Locations

Study Contact

Zachariah DeFilipp, MD

CONTACT

(617) 726-5765

zdefilipp@mgh.harvard.edu

Principal Investigator

Zachariah DeFilipp, MD

PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Study Locations (Sites)

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Collaborators and Investigators

Sponsor: Massachusetts General Hospital

Zachariah DeFilipp, MD, PRINCIPAL_INVESTIGATOR, Massachusetts General Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-06-06

Study Completion Date2027-09-01

Study Record Updates

Study Start Date2024-06-06

Study Completion Date2027-09-01

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Acute Myeloid Leukemia
Acute Myeloid Leukemia in Remission
NPM1 Mutation
KMT2A Rearrangement