A Study to Evaluate KO-539 to Treat Relapsed or Refractory Acute Myeloid Leukemia

Overview

About this study

The purpose of this study is to determine the maximum tolerated dose (MTD) of KO-539, a menin-MLL(KMT2A) inhibitor, in patients with refractory or relapsed  acute myeloid leukemia (AML) who have failed or are ineligible for any approved standard of care therapies, including hematopoietic stem cell transplantation (HSCT).

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

The following Inclusion and Exclusion Criteria are applicable to patients in both Part 1a - Dose-Escalation and Part 1b - Validation/ Cohort Expansion unless otherwise specified.

Inclusion Criteria:

  • Refractory or relapsed AML defined as the reappearance of > 5% blasts in the bone marrow and who have also failed or are not eligible for any approved standard of care therapies, including HSCT.
  • ≥ 18 years of age.
  • Read, understood, and provided written informed consent and, if applicable, Health Insurance Portability and Accountability Act (HIPAA) authorization after the nature of the study has been fully explained and must be willing to comply with all study requirements and procedures including serial bone marrow and peripheral blood sampling.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
  • Adequate organ function including:
    • creatinine ≤ 2.0 × upper limit of normal (ULN) OR creatinine clearance ≥ 40 mL/min using the Cockcroft-Gault equation;
    • serum bilirubin ≤ 1.5 × ULN (unless known Gilbert’s syndrome or secondary to leukemic disease); aspartate aminotransferase and alanine aminotransferase ≤ 2.0 × ULN.
  • Peripheral white blood cell (WBC) counts ≤ 30,000/μL. Patients are allowed to receive hydroxyurea to control and maintain WBC count prior to enrollment and can continue on hydroxyurea through Cycle 1 Day 28 or until first disease assessment. After which, approval by Kura Medical Monitor is required.
  • Women of childbearing potential (WOCBP) must be willing to use a highly effective method of contraception throughout the study and study follow-up or for at least 90 days after the last dose of study treatment.
    • NOTE: A woman is considered to be of non-childbearing potential if she meets one of the following criteria:
    • post-menopausal with at least 12 months of spontaneous amenorrhea;
    • has had a bilateral oophorectomy; or
    • has had a hysterectomy.
  • Males with female partners of childbearing potential must agree to use a highly effective method of contraception throughout the study and study follow-up or for at least 90 days after the last dose of study treatment. All men with female partners of childbearing potential will be instructed to contact the Investigator immediately if their partner becomes pregnant at any time during study participation. All men must agree not to donate semen throughout the study and for 90 days after the last dose of study treatment.

In Part 1b Dose-Validation/ Cohort Expansion, patients must meet ALL of the above inclusion criteria as well as:

  • Adult patients that have documented specific genetic subtypes determined by local institutional genomic testing and defined as either lysine[K]-specific methyltransferase 2- rearranged (KMT2A-r) or nucleophosmin 1-mutant (NPM1-m).

Exclusion Criteria:

  • Patient has a diagnosis of acute promyelocytic leukemia.
  • Patient has a diagnosis of chronic myelogenous leukemia in blast crisis.
  • Donor lymphocyte infusion 1000 and platelet count >n100,000).
  • Patients on 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 graft-versus-host disease (GVHD) is allowed and stable steroid doses less than or equal to 20 mg of prednisone daily is permitted with Kura Medical Monitor approval.
  • Grade > 2 active GVHD, moderate or severe limited chronic GVHD, or extensive chronic GVHD of any severity.
  • Patient has 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 KO-539.
  • Patients who have not recovered to NCI CTCAE ≤ v5.0 Grade 2 from all acute toxicities or deemed back to a stable baseline.
  • Patient requires treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450 (CYP)3A4 with the exception of antibiotics, antifungals, and antivirals that are used as standard of care to prevent or treat infections. Other such drugs that are considered absolutely essential for the care of the patient should be discussed on a caseby-case basis with the Kura Medical Monitor.
  • Patient has a known detectable viral load for human immunodeficiency virus or hepatitis C, or evidence of a hepatitis B surface antigen, all being indicative of active infection.
  • Patient has a 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).
  • Patient has an active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection.
  • 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 (New York Heart Association [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.
  • Mean corrected QT interval by Fredericia’s formula (QTcF) >480 ms on triplicate electrocardiograms (ECGs) performed within 5 minutes of each other. Please refer to the following Credible Meds web page for a list of drugs that prolong QT and/or increase risk of torsades de pointes, https://crediblemeds.org/pdftemp/pdf/CombinedList.pdf.
  • Major surgery within 4 weeks prior to the first dose of study treatment. Surgery requiring local/epidural anesthesia must be completed at least 72 hours before study drug administration and patients should be recovered.
  • Underlying medical condition that, in the Principal Investigator’s opinion, will make the administration of study treatment hazardous or obscure the interpretation of toxicity determination or adverse events (AEs).
  • Women who are pregnant or lactating. All female patients with reproductive potential must have a negative pregnancy test prior to starting treatment.
  • Known alcohol or drug abuse or dependence.

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status Contact

Rochester, Minn.

Mayo Clinic principal investigator

Mrinal Patnaik, M.B.B.S.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

Jacksonville, Fla.

Mayo Clinic principal investigator

James Foran, M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

(855) 776-0015

More information

Publications

Publications are currently not available

Study Results Summary

Not yet available

Supplemental Study Information

Not yet available

Additional contact information

Cancer-related trials contact form

Phone: 855-776-0015 (toll-free)

International patient clinical studies questions