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Trial record 1 of 1 for:    KO-539
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First in Human Study of KO-539 in Relapsed or Refractory Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT04067336
Recruitment Status : Recruiting
First Posted : August 26, 2019
Last Update Posted : May 2, 2022
Sponsor:
Information provided by (Responsible Party):
Kura Oncology, Inc.

Brief Summary:
This first-in-human (FIH) dose-escalation and dose-validation/expansion study will assess ziftomenib (KO-539), a menin-MLL(KMT2A) inhibitor, in patients with relapsed or refractory acute myeloid leukemia (AML).

Condition or disease Intervention/treatment Phase
Advanced Malignant Neoplasm Acute Myeloid Leukemia Mixed Lineage Leukemia Mixed Lineage Acute Leukemia Acute Leukemia of Ambiguous Lineage Mixed Phenotype Acute Leukemia Drug: Ziftomenib Phase 1 Phase 2

Detailed Description:

This Phase 1/2a, first-in-human (FIH), open-label, dose-escalation and dose-validation/expansion study will assess ziftomenib (KO-539), a menin-MLL(KMT2A) inhibitor, in patients with relapsed or refractory acute myeloid leukemia (AML).

The dose-escalation part of the study (part 1a) will determine the maximal tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D).

The dose-validation/expansion part of the study (part 1b) will determine the safety, tolerability, and minimal biologically effective dose of ziftomenib (KO-539) in dosing cohorts which have demonstrated early biological activity and have been determined to be safe in the dose-escalation part.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1/2A First in Human Study of the Menin-MLL(KMT2A) Inhibitor KO-539 in Patients With Relapsed or Refractory Acute Myeloid Leukemia
Actual Study Start Date : September 12, 2019
Estimated Primary Completion Date : June 30, 2022
Estimated Study Completion Date : December 31, 2022


Arm Intervention/treatment
Experimental: Part 1a: Dose-Escalation Drug: Ziftomenib
Oral administration
Other Name: KO-539

Experimental: Part 1b: Dose-Validation Expansion

Cohort 1: KMT2A-r / NPM1-m patients will receive a dose previously studied in Part 1a

Cohort 2: KMT2A-r / NPM1-m patients will receive a dose previously studied in Part 1a

Drug: Ziftomenib
Oral administration
Other Name: KO-539




Primary Outcome Measures :
  1. Part 1a: Maximal tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) [ Time Frame: Dose Limiting Toxicities (DLTs) will be evaluated during the first 28 days (1 cycle) ]
    MTD is defined as the highest dose that is not expected to cause dose limiting toxicity (DLT) in more than 20% of patients.

  2. Part 1b: Number of patients that experience Adverse Events (AEs) and Serious Adverse Events (SAEs). [ Time Frame: During treatment and up to approximately 28 days after treatment discontinuation, or until immediately before the initiation of another anticancer therapy, whichever occurs first. ]
    Assessed by NCI-CTCAE v5.0

  3. Part 1b: Minimal biologically effective dose [ Time Frame: Up to 6 months following end of treatment ]
    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


Secondary Outcome Measures :
  1. Part 1a: Number of patients that experience Adverse Events (AEs) and Serious Adverse Events (SAEs). [ Time Frame: During treatment and up to approximately 28 days after treatment discontinuation, or until immediately before the initiation of another anticancer therapy, whichever occurs first. ]
    Assessed by NCI-CTCAE v5.0

  2. Part 1a: Tmax [ Time Frame: Cycle 1 and Cycle 2. Each cycle is 28 days. ]
    Time to observed maximum plasma concentration of ziftomenib (KO-539)

  3. Part 1a: AUC(0-last) [ Time Frame: Cycle 1 and Cycle 2. Each cycle is 28 days. ]
    Area under the plasma concentration-time curve from time 0 to time of last measurable concentration of ziftomenib (KO-539)

  4. Part 1a: Cmax [ Time Frame: Cycle 1 and Cycle 2. Each cycle is 28 days. ]
    Maximum plasma concentration of ziftomenib (KO-539)

  5. Parts 1a and 1b: Composite definition of complete remission (CR) and complete remission with partial hematologic recovery (CRh) [ Time Frame: Up to 6 months following discontinuation of treatment ]
    To assess the CR (CR+CRh) rate

  6. Parts 1a and 1b: Complete response (CR) with and without minimal residual disease (MRD) [ Time Frame: Up to 6 months following discontinuation of treatment ]
    To assess the CR rate with and without MRD

  7. Parts 1a and 1b: Duration of remission (DOR) [ Time Frame: Up to 6 months following discontinuation of treatment ]
    To assess the DOR

  8. Part 1b: Transfusion independence (TI) [ Time Frame: Up to 6 months following discontinuation of treatment ]
    To assess transfusion independence

  9. Part 1b: Relapse-free survival (RFS) [ Time Frame: Up to 6 months following discontinuation of treatment ]
    To assess relapse-free survival

  10. Part 1b: Overall survival [ Time Frame: Up to 12 months following discontinuation of treatment ]
    To assess overall survival



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria (Parts 1a and 1b):

  1. 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.
  2. ≥ 18 years of age.
  3. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  4. Adequate liver and kidney function according to protocol requirements.
  5. Peripheral white blood cell (WBC) counts ≤ 30,000/μL.
  6. 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.
  7. 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.

In Part 1b Dose-Validation /Cohort Expansion, patient must have documented specific genetic subtypes determined by testing and defined as either KMT2A-r or NPM1-m.

Key Exclusion Criteria (Parts 1a and 1b):

  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 (i.e. ANC >1,000 and platelet count > 100,000).
  6. Receiving immunosuppressive therapy post HSCT at the time of screening (must be off all immunosuppression therapy for at least 2 weeks).
  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, or 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 (KO-539) or within 5 drug half-lives (whichever is longer) prior to the first dose of study drug.
  9. 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.
  10. Detectable viral load for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen indicative of active infection.
  11. Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection.
  12. 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.
  13. Mean QTcF >480 ms on triplicate ECG.
  14. Major surgery within 4 weeks prior to the first dose of study treatment.
  15. Women who are pregnant or lactating. All female patients with reproductive potential must have a negative pregnancy test prior to starting treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04067336


Contacts
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Contact: Mary Pevear 781-346-9905 mpevear@kuraoncology.com
Contact: Mollie Leoni, MD 617-302-9755 mleoni@kuraoncology.com

Locations
Show Show 26 study locations
Sponsors and Collaborators
Kura Oncology, Inc.
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Kura Oncology, Inc.
ClinicalTrials.gov Identifier: NCT04067336    
Other Study ID Numbers: KO-MEN-001
First Posted: August 26, 2019    Key Record Dates
Last Update Posted: May 2, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kura Oncology, Inc.:
AML
Hematological malignancy
KMT2A
NPM1
Menin
MLLr
Leukemia
Acute Leukemia
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Leukemia, Biphenotypic, Acute
Acute Disease
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases