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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04067336
Other study ID # KO-MEN-001
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date September 12, 2019
Est. completion date September 30, 2025

Study information

Verified date March 2024
Source Kura Oncology, Inc.
Contact Clinical Operations
Phone 858 500 8800
Email KO-MEN-001@kuraoncology.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess ziftomenib, a menin-MLL(KMT2A) inhibitor, in patients with relapsed or refractory acute myeloid leukemia (AML) as part of Phase 1. In Phase 2, assessment of ziftomenib will continue in patients with NPM1-m AML.


Description:

This Phase 1/2, first-in-human (FIH), open-label, dose-escalation and dose-validation/expansion study will assess ziftomenib, a menin-MLL(KMT2A) inhibitor, in patients with relapsed or refractory acute myeloid leukemia (AML). The dose-escalation part of the study (Phase 1a) will determine the maximal tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D). The dose-validation/expansion part of the study (Phase 1b) will determine the safety, tolerability, and minimal biologically effective dose of ziftomenib in dosing cohorts which have demonstrated early biological activity and have been determined to be safe in the dose-escalation phase. The Phase 2 portion of the study will determine the safety, tolerability, and anti-leukemia activity of ziftomenib in patients with NPM1-m AML.


Recruitment information / eligibility

Status Recruiting
Enrollment 199
Est. completion date September 30, 2025
Est. primary completion date September 30, 2024
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Key Inclusion Criteria: Patients with refractory or relapsed AML defined as the reappearance of = 5% blasts in the bone marrow and who have also failed or are ineligible for any approved standard of care therapies, including HSCT. 1. Phase 1b: 1. Patients with a documented lysine[K]-specific methyltransferase 2-rearrangement (KMT2A-r), or 2. Patients with a documented nucleophosmin 1 mutation (NPM1-m) 2. Phase 2: a. Patients with a documented nucleophosmin 1 mutation (NPM1-m) 3. = 18 years of age. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a life expectancy of at least 2 months. 5. Adequate liver and kidney function according to protocol requirements. 6. Peripheral white blood cell (WBC) counts = 30,000/µL. Patients may receive hydroxyurea to control and maintain white blood cell count prior to enrollment. 7. Women of childbearing potential must be willing to use a highly effective method of contraception throughout the study and for at least 180 days after the last dose of study treatment. 8. Males with female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and for at least 90 days after the last dose of study treatment. Key Exclusion Criteria: 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) 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. 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.

Study Design


Intervention

Drug:
Ziftomenib
Oral administration

Locations

Country Name City State
Belgium UZ Brussel Jette
Belgium AZ Delta - Campus Rumbeke Roeselare
Canada Queen Elizabeth II Health Sciences Centre Halifax Nova Scotia
Canada Hopital Maisonneuve-Rosemont Montréal Quebec
Canada CHU de Quebec - Universite Laval, Hopital de l'Enfant - Jesus Québec Quebec
Canada Hopital de l'Enfant-Jesus - Centre Integre en Cancerologie du CHU de Quebec - Universite Laval Québec Quebec
France CHU de Lille Lille
France CHU de Nantes Nantes
France Hopital Saint Louis Paris
France Magendie Hopital Haut-Leveque Pessac
France Centre Hospitalier Lyon Sud Pierre-Bénite
France Institut Gustave Roussy Villejuif
Germany Charitè-Campus Benjamin Franklin Berlin
Germany University Medicine Greifswald Greifswald
Germany Medizinische Hochsschule Hannover Hannover
Germany Johannes Gutenberg - University Mainz Mainz
Italy Institute of Hematology and Medical Oncology "L. and A. Seragnoli" Bologna
Italy IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" Meldola
Italy UO Ematologia Ospedale di Ravenna Ravenna
Italy Institution Fondazione Policlinico Tor Vergata Roma
Spain Hospital Universitari Vall d'Hebron Barcelona
Spain Universitat de Barcelona Barcelona
Spain Hospital Universitario HM Sanchinarro Madrid
Spain MD Anderson Cancer Center Madrid
Spain Hospital Universitario Central de Asturias Oviedo
Spain Hospital Universitario Virgen del Rocio Sevilla
Spain Hospital Universitari i Politecnic La Fe Valencia
United Kingdom Beatson West of Scotland Cancer Centre Glasgow
United Kingdom St. George's Hospital London
United States University of Michigan Hospitals Ann Arbor Michigan
United States University of Maryland Greenebaum Comprehensive Cancer Center Baltimore Maryland
United States Massachusetts General Hospital Boston Massachusetts
United States Roswell Park Comprehensive Cancer Center Buffalo New York
United States Northwestern University Chicago Illinois
United States Harold C. Simmons Comprehensive Cancer Center - UT Southwestern Medical Center Dallas Texas
United States Karmanos Cancer Institute Detroit Michigan
United States Duke Cancer Institute Durham North Carolina
United States Banner MD Anderson Cancer Center Gilbert Arizona
United States Hackensack University Medical Center - John Theurer Cancer Center Hackensack New Jersey
United States MD Anderson Cancer Center Houston Texas
United States Indiana University Melvin and Bren Simon Comprehensive Cancer Center Indianapolis Indiana
United States Mayo Clinic Jacksonville Florida
United States UCLA Bowyer Oncology Center Los Angeles California
United States University of Southern California Los Angeles California
United States Vanderbilt-Ingram Cancer Center Nashville Tennessee
United States The Mount Sinai Hospital New York New York
United States Weill Cornell Medical College - NY Presbyterian Hospital New York New York
United States Oklahoma University Health - Stephenson Cancer Center Oklahoma City Oklahoma
United States Mayo Clinic Phoenix Arizona
United States UPMC Hillman Cancer Center Pittsburgh Pennsylvania
United States Mayo Clinic Rochester Minnesota
United States Fred Hutchinson Cancer Research Center Seattle Washington

Sponsors (1)

Lead Sponsor Collaborator
Kura Oncology, Inc.

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  France,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type Measure Description Time frame Safety issue
Primary Phase 1a: Maximal tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) MTD is defined as the highest dose that is not expected to cause dose limiting toxicity (DLT) in more than 20% of patients. Dose Limiting Toxicities (DLTs) will be evaluated during the first 28 days (1 cycle)
Primary Phase 1b: Number of patients that experience Adverse Events (AEs) and Serious Adverse Events (SAEs). Assessed by NCI-CTCAE v5.0 During treatment and up to approximately 28 days after treatment discontinuation, or until immediately before the initiation of another anticancer therapy, whichever occurs first.
Primary Phase 1b: Minimal biologically effective dose Minimal biologically effective dose in dosing cohorts which have demonstrated biological activity and have been determined to be safe as a part of Part 1a Up to 12 months following end of treatment
Primary Phase 2: Evidence of anti-leukemia activity Anti-leukemia activity is assessed by the CR (CR+CRh) rate 12 months following end of treatment
Secondary Phase 1a: Number of patients that experience Adverse Events (AEs) and Serious Adverse Events (SAEs). Assessed by NCI-CTCAE v5.0 During treatment and up to approximately 28 days after treatment discontinuation, or until immediately before the initiation of another anticancer therapy, whichever occurs first.
Secondary Phase 1a: Tmax Time to observed maximum plasma concentration of ziftomenib and/or its metabolites Cycle 1 and Cycle 2. Each cycle is 28 days.
Secondary Phase 1a: AUC(0-last) Area under the plasma concentration-time curve from time 0 to time of last measurable concentration of ziftomenib and/or its metabolites Cycle 1 and Cycle 2. Each cycle is 28 days.
Secondary Phase 1a: Cmax Maximum plasma concentration of ziftomenib and/or its metabolites Cycle 1 and Cycle 2. Each cycle is 28 days.
Secondary Phases 1a, 1b, and 2: Composite definition of complete remission (CR) and complete remission with partial hematologic recovery (CRh) To assess the CR (CR+CRh) rate Up to 12 months following discontinuation of treatment
Secondary Phases 1a, 1b, and 2: Complete response (CR) with and without minimal residual disease (MRD) To assess the CR rate with and without MRD Up to 12 months following discontinuation of treatment
Secondary Phases 1a, 1b, and 2: Duration of remission (DOR) To assess the DOR Up to 12 months following discontinuation of treatment
Secondary Phases 1a, 1b, and 2: Transfusion independence (TI) To assess transfusion independence Up to 12 months following discontinuation of treatment
Secondary Phases 1a, 1b, and 2: Event-free survival (EFS) To assess event-free survival Up to 12 months following discontinuation of treatment
Secondary Phases 1a, 1b, and 2: Overall survival To assess overall survival Up to 12 months following discontinuation of treatment
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