NCT04067336
First in Human Study of Ziftomenib in Relapsed or Refractory Acute Myeloid Leukemia
Active, Not Recruiting
PHASE1Ages 18+InterventionalTreatmentKura Oncology, Inc.
~263 participants
Updated 2026-05-13 on ClinicalTrials.gov
What's tested:ZiftomenibMidazolamItraconazole
At a glance
Recruiting sites
0 of 43 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Phase 1a: Maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D)
Measured over Dose Limiting Toxicities (DLTs) will be evaluated during the first 28 days (1 cycle)
+16 more outcomes measured
Conditions
Where it's being run
43 sites across 23 statesSpain7
France6
Italy4
New York3
Michigan2
Texas2
Quebec2
Germany2
Who to contact
This trial hasn't published a contact. View it on ClinicalTrials.gov
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Patients with a documented lysine\[K\]-specific methyltransferase 2-rearrangement (KMT2A-r), or
Patients with a documented nucleophosmin 1 mutation (NPM1-m) 2. Phase 2:
Patients with a documented nucleophosmin 1 mutation (NPM1-m) 3. Sub-studies:
Sub-studies 1 and 2: Patients with R/R AML with NPM1-m or other mutations associated with MEIS1 overexpression.
Sub-study 3: Patients with R/R Acute Lymphoblastic Leukemia (ALL) with KMT2A-r.
Sub-study 4: Patients with R/R AML with mutations associated with MEIS1 overexpression. 4. ≥ 18 years of age. 5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a life expectancy of at least 2 months. 6. Adequate liver and kidney function according to protocol requirements. 7. Peripheral white blood cell (WBC) counts ≤ 30,000/μL. Patients may receive hydroxyurea to control and maintain white blood cell count prior to enrollment. 8. 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. 9. 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.
Exclusion
Phase 1a, 1b, 2, and sub-studies 3 and 4: 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.
Sub-studies 1 and 2: No exceptions will be allowed except for the use of moderate CYP3A4 antifungal prophylaxis such as fluconazole or isavuconazole which is at steady state on Cycle 1 Day 1 and will continue through the completion of PKs on Cycle 1 Day 15 (for sub-study 1) or Cycle 1 Day 18 (for sub-study 2). 11. Detectable viral load for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen indicative of active infection. Patients with controlled disease will not be excluded from study enrollment. 12. 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). 13. Active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection. 14. 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. 15. Mean QTcF \>480 ms on triplicate ECG. 16. Major surgery within 4 weeks prior to the first dose of study treatment. 17. Women who are pregnant or lactating. All female patients with reproductive potential must have a negative serum pregnancy test within 72 hours prior to starting treatment. 18. For sub-studies 1 and 2: Any intake of grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade, or other products containing grapefruit or Seville oranges within 7 days of the first administration of ziftomenib until the end of Cycle 1. 19. For sub-studies 1 and 2: Moderate (Child-Pugh class B) or severe (Child-Pugh class C) hepatic impairment.
What this trial measures
- Phase 1a: Maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D)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.
- Phase 1b: Number of patients who experience Adverse Events (AEs) and Serious Adverse Events (SAEs)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
- Phase 1b: Minimum biologically effective doseFor at least 12 months following end of treatment
Minimum biologically effective dose in dosing cohorts which have demonstrated biological activity and have been determined to be safe as a part of Part 1a
- Phase 1a, 1b, and 2: Evidence of anti-leukemia activityFor at least 12 months following end of treatment
Assessed by the CR + CRh rate
- Sub-study 1: Time to observed maximum plasma concentration (Tmax) of ziftomenib and midazolamCycle 1 on Days 1 and 15 at predose and postdose
Tmax of ziftomenib, its metabolites, midazolam, and 1-hydroxymidazolam
- Sub-study 1: Area under the plasma concentration-time curve from time 0 to time t (AUC0-t) of ziftomenib and midazolamCycle 1 on Days 1 and 15 at predose and postdose
AUC0-t of ziftomenib, its metabolites, midazolam, and 1-hydroxymidazolam
- Sub-study 1: Maximum observed plasma concentration (Cmax) of ziftomenib and midazolamCycle 1 on Days 1 and 15 at predose and postdose
Cmax of ziftomenib, its metabolites, midazolam, and 1-hydroxymidazolam
- Sub-study 2: Time to observed maximum plasma concentration (Tmax) of ziftomenib and itraconazoleCycle 1 on Days 1, 15, and 22 at predose and postdose
Tmax of ziftomenib, its metabolites, and itraconazole
- Sub-study 2: Area under the plasma concentration-time curve from time 0 to time t (AUC0-t) of ziftomenib and itraconazoleCycle 1 on Days 1, 15, and 22 at predose and postdose
AUC0-t of ziftomenib, its metabolites, and itraconazole
- Sub-study 2: Maximum observed plasma concentration (Cmax) of ziftomenib and itraconazoleCycle 1 on Days 1, 15, and 22 at predose and postdose
Cmax of ziftomenib, its metabolites, and itraconazole
- Sub-study 3: Minimum biologically effective dose (MBED) and/or the recommended Phase 2 dose (RP2D)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 the number of patients that experience Adverse Events (AEs) and Serious Adverse Events (SAEs) per NCI-CTCAE v5.0
- Sub-study 3: Minimum biologically effective dose (MBED) and/or the recommended Phase 2 dose (RP2D)For at least 12 months following end of treatment
Assessed by CR
- Sub-study 3: Change in Eastern Cooperative Oncology Group (ECOG) statusTimeframe: from Baseline to End of Treatment
To assess the change in ECOG status
- Sub-study 3: Time to observed maximum plasma concentration (Tmax) of ziftomenibPostdose on Cycle 1 Day 1 and Cycle 2 Day 1. Predose at Cycle 2 onwards
Tmax of ziftomenib
- Sub-study 3: Area under the plasma concentration-time curve from time 0 to time t (AUC0-t) of ziftomenibPostdose on Cycle 1 Day 1 and Cycle 2 Day 1. Predose at Cycle 2 onwards
AUC0-t of ziftomenib
- Sub-study 3: Maximum observed plasma concentration (Cmax) of ziftomenibPostdose on Cycle 1 Day 1 and Cycle 2 Day 1. Predose at Cycle 2 onwards.
Cmax of ziftomenib
- Sub-study 4: Complete remission (CR) and complete remission with partial hematologic recovery (CRh)For at least 12 months following end of treatment
To assess the CR+CRh rate