RECRUITING

First in Human Study of Ziftomenib in Relapsed or Refractory Acute Myeloid Leukemia

Conditions

Advanced Malignant Neoplasm Acute Myeloid Leukemia Mixed Lineage Leukemia Mixed Lineage Acute Leukemia Acute Leukemia of Ambiguous Lineage Mixed Phenotype Acute Leukemia Acute Lymphoblastic Leukemia AML Hematological malignancy KMT2A NPM1 Menin Leukemia Acute Leukemia ALL MLL MEIS1

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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

In this trial, ziftomenib, a menin-MLL(KMT2A) inhibitor, will be tested in patients for the first time. The trial includes a Main Study and four sub-studies. In the Main Study (including Phase 1a, Phase 1b, and Phase 2 portions), ziftomenib will be evaluated in patients with relapsed or refractory (R/R) acute myeloid leukemia (AML). The main study has completed enrollment. In Sub-studies 1 and 2, the effects of taking ziftomenib and other common drugs at the same time will be investigated in AML patients. In Sub-study 3, ziftomenib will be evaluated in patients with R/R acute lymphoblastic leukemia (ALL). In Sub-study 4, ziftomenib will be evaluated in patients with R/R AML with certain genetic mutations.

Official Title

A Phase 1/2 First in Human Study of the Menin-MLL(KMT2A) Inhibitor KO-539 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

Quick Facts

Study Start:2019-09-12

Study Completion:2028-10-16

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04067336

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
1. Phase 1b: * Patients with a documented lysine\[K\]-specific methyltransferase 2-rearrangement (KMT2A-r), or * Patients with a documented nucleophosmin 1 mutation (NPM1-m) 2. Phase 2: * Patients with a documented nucleophosmin 1 mutation (NPM1-m) 3. Sub-studies: * Sub-studies 1 and 2: Patients with R/R AML with NPM1-m or other mutations associated with MEIS1 overexpression. * Sub-study 3: Patients with R/R Acute Lymphoblastic Leukemia (ALL) with KMT2A-r. * Sub-study 4: Patients with R/R AML with mutations associated with MEIS1 overexpression. 4. ≥ 18 years of age. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a life expectancy of at least 2 months. 6. Adequate liver and kidney function according to protocol requirements. 7. Peripheral white blood cell (WBC) counts ≤ 30,000/μL. Patients may receive hydroxyurea to control and maintain white blood cell count prior to enrollment. 8. Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and for at least 187 days after the last dose of study treatment. 9. Males with female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 97 days after the last dose of study treatment.	1. Diagnosis of acute promyelocytic leukemia. 2. Diagnosis of chronic myelogenous leukemia in blast crisis. 3. Donor lymphocyte infusion \< 30 days prior to study entry. 4. Clinically active central nervous system (CNS) leukemia. 5. Undergone HSCT and have not had adequate hematologic recovery. 6. Receiving immunosuppressive therapy post HSCT within 2 weeks of Cycle 1 Day 1. 7. Grade ≥ 2 active graft-versus-host disease (GVHD), moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity. 8. Received chemotherapy immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) \< 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug. 9. Not recovered to \< Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) from all acute toxicities or deemed back to a stable baseline. 10. Treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450-isozyme 3A4 (CYP3A4), as follows: * Phase 1a, 1b, 2, and sub-studies 3 and 4: with the exception of antibiotics, antifungals, and antivirals that are used as standard of care or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient. * Sub-studies 1 and 2: No exceptions will be allowed except for the use of moderate CYP3A4 antifungal prophylaxis such as fluconazole or isavuconazole which is at steady state on Cycle 1 Day 1 and will continue through the completion of PKs on Cycle 1 Day 15 (for sub-study 1) or Cycle 1 Day 18 (for sub-study 2). 11. Detectable viral load for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen indicative of active infection. Patients with controlled disease will not be excluded from study enrollment. 12. Pre-existing disorder predisposing the patient to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML). 13. Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection. 14. Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within the past 6 months, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the first dose of study treatment. 15. Mean QTcF \>480 ms on triplicate ECG. 16. Major surgery within 4 weeks prior to the first dose of study treatment. 17. Women who are pregnant or lactating. All female patients with reproductive potential must have a negative serum pregnancy test within 72 hours prior to starting treatment. 18. For sub-studies 1 and 2: Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of ziftomenib until the end of Cycle 1. 19. For sub-studies 1 and 2: Moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment.

Inclusion Criteria

Exclusion Criteria

1. Phase 1b:
* Patients with a documented lysine\[K\]-specific methyltransferase 2-rearrangement (KMT2A-r), or
* Patients with a documented nucleophosmin 1 mutation (NPM1-m)
2. Phase 2:
* Patients with a documented nucleophosmin 1 mutation (NPM1-m)
3. Sub-studies:
* Sub-studies 1 and 2: Patients with R/R AML with NPM1-m or other mutations associated with MEIS1 overexpression.
* Sub-study 3: Patients with R/R Acute Lymphoblastic Leukemia (ALL) with KMT2A-r.
* Sub-study 4: Patients with R/R AML with mutations associated with MEIS1 overexpression.
4. ≥ 18 years of age.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a life expectancy of at least 2 months.
6. Adequate liver and kidney function according to protocol requirements.
7. Peripheral white blood cell (WBC) counts ≤ 30,000/μL. Patients may receive hydroxyurea to control and maintain white blood cell count prior to enrollment.
8. Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and for at least 187 days after the last dose of study treatment.
9. Males with female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 97 days after the last dose of study treatment.

1. Diagnosis of acute promyelocytic leukemia.
2. Diagnosis of chronic myelogenous leukemia in blast crisis.
3. Donor lymphocyte infusion \< 30 days prior to study entry.
4. Clinically active central nervous system (CNS) leukemia.
5. Undergone HSCT and have not had adequate hematologic recovery.
6. Receiving immunosuppressive therapy post HSCT within 2 weeks of Cycle 1 Day 1.
7. Grade ≥ 2 active graft-versus-host disease (GVHD), moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.
8. Received chemotherapy immunotherapy, radiotherapy, or any ancillary therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) \< 14 days prior to the first dose of ziftomenib or within 5 drug half-lives prior to the first dose of study drug.
9. Not recovered to \< Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) from all acute toxicities or deemed back to a stable baseline.
10. Treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450-isozyme 3A4 (CYP3A4), as follows:
* Phase 1a, 1b, 2, and sub-studies 3 and 4: with the exception of antibiotics, antifungals, and antivirals that are used as standard of care or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient.
* Sub-studies 1 and 2: No exceptions will be allowed except for the use of moderate CYP3A4 antifungal prophylaxis such as fluconazole or isavuconazole which is at steady state on Cycle 1 Day 1 and will continue through the completion of PKs on Cycle 1 Day 15 (for sub-study 1) or Cycle 1 Day 18 (for sub-study 2).
11. Detectable viral load for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen indicative of active infection. Patients with controlled disease will not be excluded from study enrollment.
12. Pre-existing disorder predisposing the patient to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML).
13. Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection.
14. Significant cardiovascular disease including unstable angina pectoris, uncontrolled hypertension or arrhythmia, history of cerebrovascular accident including transient ischemic attack within the past 6 months, congestive heart failure (NYHA Class III or IV) related to primary cardiac disease, ischemic or severe valvular heart disease, or a myocardial infarction within 6 months prior to the first dose of study treatment.
15. Mean QTcF \>480 ms on triplicate ECG.
16. Major surgery within 4 weeks prior to the first dose of study treatment.
17. Women who are pregnant or lactating. All female patients with reproductive potential must have a negative serum pregnancy test within 72 hours prior to starting treatment.
18. For sub-studies 1 and 2: Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of ziftomenib until the end of Cycle 1.
19. For sub-studies 1 and 2: Moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment.

Contacts and Locations

Study Contact

Clinical Operations

CONTACT

617-588-3755

KO-MEN-001@kuraoncology.com

Study Locations (Sites)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234

United States

Mayo Clinic

Phoenix, Arizona, 85054

United States

University of Southern California

Los Angeles, California, 90033

United States

UCLA Ronald Reagan Medical Center

Los Angeles, California, 90095

United States

Mayo Clinic

Jacksonville, Florida, 32224

United States

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611

United States

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202

United States

University of Maryland Greenebaum Comprehensive Cancer Center

Baltimore, Maryland, 21201

United States

Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

University of Michigan Hospitals

Ann Arbor, Michigan, 48109

United States

Karmanos Cancer Institute

Detroit, Michigan, 48201

United States

Mayo Clinic

Rochester, Minnesota, 55905

United States

Hackensack University Medical Center - John Theurer Cancer Center

Hackensack, New Jersey, 07601

United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14203

United States

Weill Cornell Medical College - NY Presbyterian Hospital

New York, New York, 10021

United States

The Mount Sinai Hospital

New York, New York, 10029

United States

Duke Cancer Institute

Durham, North Carolina, 27710

United States

Oklahoma University Health - Stephenson Cancer Center

Oklahoma City, Oklahoma, 73117

United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

United States

Vanderbilt-Ingram Cancer Center

Nashville, Tennessee, 37232

United States

Harold C. Simmons Comprehensive Cancer Center - UT Southwestern Medical Center

Dallas, Texas, 75390

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109

United States

Collaborators and Investigators

Sponsor: Kura Oncology, Inc.

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 Date2019-09-12

Study Completion Date2028-10-16

Study Record Updates

Study Start Date2019-09-12

Study Completion Date2028-10-16

Terms related to this study

Keywords Provided by Researchers

AML
Hematological malignancy
KMT2A
NPM1
Menin
Leukemia
Acute Leukemia
ALL
MLL
Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
MEIS1

Additional Relevant MeSH Terms

Advanced Malignant Neoplasm
Acute Myeloid Leukemia
Mixed Lineage Leukemia
Mixed Lineage Acute Leukemia
Acute Leukemia of Ambiguous Lineage
Mixed Phenotype Acute Leukemia
Acute Lymphoblastic Leukemia