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A Phase 1/2 First in Human Study of the Menin-MLL (KMT2A) Inhibitor KO-539 in Patients with Relapsed or Refractory Acute Myeloid Leukemia
EU CTIS ID: 2023-510509-17-00
What this study is testing
Phase 1 Part 1a: Dose-Escalation - To determine the MTD and/or the RP2D of ziftomenib in patients with R/R AML Phase 1 Part 1b: Dose-Validation/ Cohort Expansion - Determine the safety, tolerability and MBED of ziftomenib in biomarker specific dosing cohorts, which have demonstrated early biological activity and have been determined to be safe as part of the dose-escalation phase Phase 2: - Assess evidence of ALA of ziftomenib in patients with NPM1-m R/R AML Sub study 2: - will evaluate the effect of CYP3A4 inhibition on ziftomenib exposure in patients with R/R AML with mutations associated with MEIS1 overexpression - To confirm adequate itraconazole exposure Sub-Study 3: - Determine the safety, tolerability, and MBED/RP2D of ziftomenib in patients with R/R KMT2A-r ALL Sub study 4: - Assess evidence of clinical activity of ziftomenib according to the 2022 ELN Recommendations for AML and the US FDA Guidance for Industry for AML in patients with R/R AML with mutations associated with MEIS1 overexpression.
- Phase I and Phase II (Integrated)- First administration to humans
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 1. Relapsed/refractory (R/R) acute myeloid leukemia (AML) defined as those who have also failed or are not appropriate for any approved standard-of-care (SOC) therapies or hematopoietic stem cell transplant (HSCT)with reappearance of ≥ 5% blasts in the bone marrow (BM)
- 2. ≥ 18 years of age
- 3. Eastern Cooperative Oncology Group performance status of ≤ 2, and a life expectancy of at least 2 months
- 4. Peripheral white blood cell counts ≤ 30,000/μL
You likely can't join if
- 1. Diagnosis of acute promyelocytic leukemia or chronic myelogenous leukemia in blast crisis
- 10. Has an active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection
- 11. 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 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
- 12. Mean corrected QT interval by Fredericia's formula > 480 ms on triplicate electrocardiograms
- 2. Donor lymphocyte infusion < 30 days prior to study entry
- 3. Clinically active central nervous system (CNS) leukemia
See the full eligibility criteria
- 1. Relapsed/refractory (R/R) acute myeloid leukemia (AML) defined as those who have also failed or are not appropriate for any approved standard-of-care (SOC) therapies or hematopoietic stem cell transplant (HSCT)with reappearance of ≥ 5% blasts in the bone marrow (BM)
- 2. ≥ 18 years of age
- 3. Eastern Cooperative Oncology Group performance status of ≤ 2, and a life expectancy of at least 2 months
- 4. Peripheral white blood cell counts ≤ 30,000/μL
- 1. Diagnosis of acute promyelocytic leukemia or chronic myelogenous leukemia in blast crisis
- 10. Has an active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection
- 11. 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 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
- 12. Mean corrected QT interval by Fredericia's formula > 480 ms on triplicate electrocardiograms
- 2. Donor lymphocyte infusion < 30 days prior to study entry
- 3. Clinically active central nervous system (CNS) leukemia
- 4. Has undergone HSCT and has not had adequate hematologic recovery (Recovery is defined as peripheral absolute neutrophil count (ANC) ≥ 1 × 10^9/L and platelets at least ≥ 50 × 10^9/L [but preferably ≥ 100 × 10^9/L] and signs of a cellular BM at any time after HSCT).
- 5. Patients on immunosuppressive therapy post HSCT must be off all immunosuppression therapy within 2 weeks of Cycle 1 Day 1
- 6. ≥ Grade 2 active acute GvHD, moderate or severe limited chronic GvHD, or extensive chronic GvHD of any severity
- 7. Has received prior menin inhibitor
- 8. Has received chemotherapy, immunotherapy, radiotherapy (unless if given for management of CNS leukemia), or any ancillary therapy that is considered to be investigational (ie, 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, whichever is shorter, to ensure that patient time without necessary AML therapy is appropriately limited
- 9. Requires treatment with concomitant drugs that are strong inducers of CYP3A4 with the exception of antibiotics, antifungals, and antivirals that are used as SOC or to prevent or treat infections. Other such drugs that are considered absolutely essential by the Investigator for the care of the patient should be discussed on a case-by-case basis with the Medical Monitor
The study team makes the final eligibility decision.
Where it's taking place
- United Kingdom
- United States
- Canada
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 65+ years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include United Kingdom; United States; Canada. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.