First in Human Study of KO-539 in Relapsed or Refractory Acute Myeloid Leukemia

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Brief Title

First in Human Study of KO-539 in Relapsed or Refractory Acute Myeloid Leukemia

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

Brief Summary

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

Detailed Description

      This Phase 1/2a, first-in-human (FIH), open-label, dose-escalation and
      dose-validation/expansion study will assess KO-539, a menin-MLL(KMT2A) inhibitor, in patients
      with refractory or relapsed acute myeloid leukemia (AML). The dose-escalation part of the
      study (part 1a) will determine the maximal tolerated dose (MTD). The
      dose-validation/expansion part of the study (part 1b) will determine the safety,
      tolerability, and minimal biologically effective dose of KO-539 in dosing cohorts which have
      demonstrated early biological activity and have been determined to be safe as part of the
      dose-escalation part.
    

Study Phase

Phase 1/Phase 2

Study Type

Interventional


Primary Outcome

Part 1a: Maximal tolerated dose (MTD).

Secondary Outcome

 Part 1a: Number of patients that experience Adverse Events (AEs) and Serious Adverse Events (SAEs).

Condition

Advanced Malignant Neoplasm

Intervention

KO-539

Study Arms / Comparison Groups

 KO-539
Description:  Part 1a: Dose Escalation
Part 1b: Dose-Validation/Expansion
Cohort 1: KMT2A/NPM1 patients will receive a dose previously studied in Part 1a
Cohort 2: KMT2A/NPM1 patients will receive a dose previously studied in Part 1a

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

90

Start Date

September 12, 2019

Completion Date

August 1, 2022

Primary Completion Date

February 1, 2022

Eligibility Criteria

        Key Inclusion Criteria:

          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. Patients are allowed to receive
             hydroxyurea to control and maintain WBC count prior to enrollment.

          6. Both men and women (of childbearing potential) enrolled in this trial must use
             adequate birth control measures during the course of the trial and for at least 90
             days after their last dose of study treatment.

        Key Exclusion Criteria:

          1. Donor lymphocyte infusion < 30 days prior to study entry.

          2. Clinically active central nervous system (CNS) leukemia.

          3. Undergone HSCT and have not had adequate hematologic recovery (i.e. ANC >1000 and
             platelet count > 100,000).

          4. Receiving immunosuppressive therapy post HSCT at the time of screening (must be off
             all immunosuppression therapy for at least 2 weeks). The use of topical steroids for
             cutaneous GVHD is allowed and stable steroid doses less than or equal to 20 mg of
             prednisone daily is permitted.

          5. Grade > 2 active graft-versus-host disease (GVHD), moderate or severe limited chronic
             GVHD, or extensive chronic GVHD of any severity.

          6. 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 KO-539
             or within 5 drug half-lives (whichever is longer) prior to the first dose of study
             drug.

          7. 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.

          8. Known detectable viral load for human immunodeficiency virus, hepatitis C, or
             hepatitis B surface antigen indicative of active infection.

          9. Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other
             infection.

         10. 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.

         11. QTcF >480 ms.

         12. Major surgery within 4 weeks prior to the first dose of study treatment.

         13. Women who are pregnant or lactating. All female patients with reproductive potential
             must have a negative pregnancy test prior to starting treatment.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

, 617-588-2609, [email protected]

Location Countries

France

Location Countries

France

Administrative Informations


NCT ID

NCT04067336

Organization ID

KO-MEN-001


Responsible Party

Sponsor

Study Sponsor

Kura Oncology, Inc.


Study Sponsor

, , 


Verification Date

July 2021