Safety and Tolerability of Ziftomenib Combinations in Patients With Relapsed/Refractory Acute Myeloid Leukemia

NCT06001788 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: KO-MEN-008
• Study Type: interventional
• Target: 171
• Locations: 3 countries
• Sites: 45

Brief Summary

The safety, tolerability, and antileukemic response of ziftomenib in combination with standard of care treatments for patients with relapsed/refractory acute myeloid leukemia will be examined with the following agents: FLAG-IDA, low-dose cytarabine, and gilteritinib.

Conditions

AML; AML With Mutated NPM1; Hematologic Malignancy; KMT2Ar; NPM1 Mutation; MLL Rearrangement; Leukemia; Acute Myeloid Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Acute Leukemia; Neoplasms by Histologic Type

Outcome Measures

Primary Outcomes (2)

• Rate of dose limiting toxicities (DLTs) per dose level

  Assessed by the NCI-CTCAE v5.0

  During the first 28 days of ziftomenib in combination with SOC treatment (1 cycle)

• Descriptive statistics of adverse events

  Assessed by the NCI-CTCAE v5.0

  First dose of ziftomenib up to and including 28 days after last dose of ziftomenib, or if the patient is lost to follow-up, whichever comes first

Secondary Outcomes (20)

• Complete remission (CR) rate for cohorts A-1, A-2, B-1, and B-2

  Up to 12 months following discontinuation of treatment

• Complete remission (CR) / Complete remission with partial hematologic recovery (CRh) rate for cohort A-3

  Up to 12 months following discontinuation of treatment

• Composite complete remission (CRc) rate

  Up to 12 months following discontinuation of treatment

• Morphologic leukemia-free state (MLFS) rate

  Up to 12 months following discontinuation of treatment

• OS

  Up to 12 months following discontinuation of treatment

Study Arms (2)

Phase 1a

EXPERIMENTAL

Oral ziftomenib; sequential cohorts of escalating dose levels of ziftomenib to identify the safety and tolerability of the combination regimens. Participants will be enrolled in 1 of 5 dose escalation cohorts: A-1: Participants with a NPM1 mutation: ziftomenib plus FLAG-IDA A-2: Participants with a NPM1 mutation: ziftomenib plus low-dose cytarabine (LDAC) A-3: Participants with a NPM1 mutation: ziftomenib plus gilteritinib B-1: Participants with a KMT2A rearrangement: ziftomenib plus FLAG-IDA B-2: Participants with a KMT2A rearrangement: ziftomenib plus low-dose cytarabine (LDAC)

Drug: Ziftomenib; Drug: Fludarabine; Drug: Idarubicin; Drug: Cytarabine; Drug: Gilteritinib; Biological: Granulocyte colony-stimulating factor

Phase 1b

EXPERIMENTAL

Oral ziftomenib; Following the determination of the maximum tolerated dose in Phase 1a, participants will be enrolled in 1 of 5 dose validation/expansion cohorts: A-1: Participants with a NPM1 mutation: ziftomenib plus FLAG-IDA A-2: Participants with a NPM1 mutation: ziftomenib plus low-dose cytarabine (LDAC) A-3: Participants with a NPM1 mutation: ziftomenib plus gilteritinib B-1: Participants with a KMT2A rearrangement: ziftomenib plus FLAG-IDA B-2: Participants with a KMT2A rearrangement: ziftomenib plus low-dose cytarabine (LDAC)

Drug: Ziftomenib; Drug: Fludarabine; Drug: Idarubicin; Drug: Cytarabine; Drug: Gilteritinib; Biological: Granulocyte colony-stimulating factor

Interventions

Ziftomenib DRUG

Oral administration

Also known as: KO-539

Phase 1a; Phase 1b

Fludarabine DRUG

Intravenous infusion

Phase 1a; Phase 1b

Idarubicin DRUG

Intravenous infusion

Phase 1a; Phase 1b

Cytarabine DRUG

Intravenous Infusion

Phase 1a; Phase 1b

Gilteritinib DRUG

Oral administration

Also known as: Xospata

Phase 1a; Phase 1b

Granulocyte colony-stimulating factor BIOLOGICAL

Subcutaneous injection

Phase 1a; Phase 1b

Eligibility Criteria

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

You may qualify if:

• Has been diagnosed with relapsed/refractory AML.
• Has a documented NPM1 mutation or KMT2A rearrangement.
• Has a documented FLT3 mutation (cA-3 only).
• Has an Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 2.
• Has adequate hepatic and renal function as defined per protocol.
• Has an ejection fraction above a protocol defined limit.
• Participant, or legally authorized representative, must be able to understand and provide written informed consent prior to the first screening procedure.
• Has agreed to use contraception as defined per protocol.

You may not qualify if:

• Has a diagnosis of acute promyelocytic leukemia or blast chronic myeloid leukemia.
• Has clinically active central nervous system leukemia.
• Has an active and uncontrolled infection.
• Has a mean corrected QT interval (QTcF) \> 480ms.
• Has uncontrolled intercurrent illness, including, but not limited to protocol defined cardiac disease.
• Has received radiation, chemotherapy, immunotherapy, or any other anticancer therapy including investigational therapy \<14 days or within 5 drug half-lives prior to the first dose of study intervention.
• Has had major surgery within 4 weeks prior to the first dose of study intervention.
• Has received a hematopoietic stem cell transplant (HSCT) and has not previously had adequate recovery per protocol defined criteria.
• Has active graft-versus-host disease (GvHD) and or on immunosuppressive drugs for the treatment of GvHD
• Participant is pregnant or lactating.

Sponsors & Collaborators

• Kura Oncology, Inc.: lead

Study Sites (45)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

RECRUITING

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90089, United States

RECRUITING

UCLA Health - Bowyer Oncology Center

Los Angeles, California, 90095, United States

RECRUITING

UC Irvine Health Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94115, United States

RECRUITING

Colorado Blood Cancer Institute

Denver, Colorado, 80218, United States

RECRUITING

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut, 06511, United States

RECRUITING

Emory Healthcare - The Emory Clinic

Atlanta, Georgia, 30322, United States

RECRUITING

Georgia Cancer Center at Augusta University

Augusta, Georgia, 30912, United States

RECRUITING

Robert H. Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

RECRUITING

Loyola University Medical Center

Maywood, Illinois, 60153, United States

RECRUITING

Simmons Cancer Institute

Springfield, Illinois, 62702, United States

WITHDRAWN

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

The University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

RECRUITING

Henry Ford Cancer Institute

Detroit, Michigan, 48202, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263, United States

RECRUITING

Northwell Health, LLC PRIME

Lake Success, New York, 11042, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

RECRUITING

Weill Cornell Medical College-NY Presbyterian Hospital

New York, New York, 10065, United States

RECRUITING

Wilmot Cancer Institute, University of Rochester

Rochester, New York, 14642, United States

RECRUITING

Stony Brook Cancer Center

Stony Brook, New York, 11794, United States

RECRUITING

Atrium Health Levine Cancer Center

Charlotte, North Carolina, 60201, United States

RECRUITING

UH Seidman Cancer Center

Cleveland, Ohio, 44106, United States

RECRUITING

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Lehigh Valley Topper Cancer Institute

Allentown, Pennsylvania, 18103, United States

WITHDRAWN

Prisma Health

Greenville, South Carolina, 29615, United States

RECRUITING

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

RECRUITING

Texas Oncology - Baylor Charles A. Sammons Cancer Center

Dallas, Texas, 75246, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

University of Vermont

Burlington, Vermont, 05401, United States

RECRUITING

University of Virginia Comprehensive Cancer Center

Charlottesville, Virginia, 22903, United States

RECRUITING

University of Washington

Seattle, Washington, 98109, United States

RECRUITING

Froedtert & Medical College Clinics

Milwaukee, Wisconsin, 53226, United States

RECRUITING

IRCCS Azienda Ospedaliero-Universitaria do Bologna - Policlinico di Sant'Orsola

Bologna, 40138, Italy

RECRUITING

Ospedale Santa Maria delle Croci

Ravenna, 48121, Italy

RECRUITING

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Roma, 00168, Italy

RECRUITING

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario Central de Asturias

Oviedo, 33011, Spain

RECRUITING

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

RECRUITING

Hospital Universitari y Politecnic La Fe

Valencia, 46026, Spain

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms; Leukemia; Leukemia, Myeloid, Acute; Leukemia, Myeloid; Neoplasms by Histologic Type

Interventions

fludarabine; Idarubicin; Cytarabine; gilteritinib; Granulocyte Colony-Stimulating Factor

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Central Study Contacts

Kura Medical Information

CONTACT

844-KURAONC (844-587-2662); medinfo@kuraoncology.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: August 7, 2023
• First Posted: August 21, 2023
• Study Start: February 22, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-04

Locations

IT (3); ES (4); US (38)