Ziftomenib with Chemotherapy for Relapsed/Refractory Acute Leukemia in Children
This study is testing a new drug called ziftomenib in combination with standard chemotherapy (cytarabine and fludarabine) for children and young adults (ages 0-21) with acute leukemia that has come back or hasn't responded to previous treatments. Specifically, this trial is for those with KMT2A-r, NPM1-m, or NUP98-r types of acute leukemia. The main goals are to find the safest and most effective dose of ziftomenib when given with chemotherapy, and to understand how the body processes ziftomenib. The study plans to enroll about 20 participants. The current status of the study is unclear.
- Study design
- This is an interventional study planning to enroll 20 participants. It is testing ziftomenib in combination with chemotherapy.
- What's involved
- Participants will receive ziftomenib as an oral capsule and cytarabine and fludarabine through an IV. Blood samples will be taken on specific days in Cycle 1 and Cycle 2 to measure ziftomenib levels.
- Compensation
- Not stated in the trial record.
- Follow-up
- Safety will be monitored from Day 1 to Day 49. Ziftomenib levels will be measured during Cycle 1 (49 days) and Cycle 2 (28 days).
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT06376162
Ziftomenib in Combination With Chemotherapy for Children With Relapsed/Refractory Acute Leukemia
Recruiting
PHASE1Ages 0–21InterventionalTreatmentPedAL BCU, LLCInvestigator-initiated
~20 participants
Updated 2025-10-20 on ClinicalTrials.gov
What's tested:ZiftomenibCytarabineFludarabine
At a glance
Recruiting sites
20 of 20 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Number of Participants Who Experience a Dose-limiting Toxicity (DLT)
Measured over Day 1 to Day 49
+1 more outcome measured
Conditions
Where it's being run
20 sites across 19 statesSpain2
California1
Colorado1
Georgia1
Illinois1
Massachusetts1
New York1
Ohio1
Who to contact
Opens a ready-to-send draft in your own email app — review before sending.
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
Age: 0-21 years (and at least 5 kg body weight), with a minimum of 80% of participants under 18 years of age.
Diagnosis: KMT2A-r, NPM1-m, or NUP98-r acute leukemia in first or greater relapse or refractory to standard (re-) induction treatment (including HSCT). Please note that genetic alteration must be confirmed by the central laboratory, or the participant will discontinue protocol therapy.
Eligible participants also must fulfill one of the following conditions:
a single bone marrow sample with at least two tests showing ≥ 1% leukemic blasts, examples of tests (confirmed by central lab) include: Flow cytometry showing leukemia ≥ 1% by multiparameter flow cytometry (MFC) confirmed by central lab.
Karyotypic abnormality as confirmed by central cytogenetic review.
FISH abnormality identical to one present at diagnosis (must be above level of sensitivity of specific FISH probe; central cytogenetic review required).
Polymerase chain reaction (PCR) or next generation sequencing (NGS)-based demonstration of validated leukemogenic lesion (e.g., fusion, mutation) in a Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory that matches initial diagnosis and is quantifiable as ≥1% confirmed by central lab. 2. Participants with combined extramedullary and bone marrow relapse (defined as above) are eligible. 3. Participants with isolated extramedullary disease (EMD) are not eligible. EMD relapse is defined as biopsy-proven extramedullary disease without bone marrow disease after documented complete response (CR) following initial therapy. Participants with isolated central nervous system (CNS) relapse are not eligible. Participants with a combined medullary/extramedullary relapse, including CNS disease, are eligible. 4. Participants with asymptomatic CNS3 disease are eligible if they do not have isolated CNS3 extramedullary relapse. 5. For participants unable to undergo bone marrow assessment, a peripheral blood absolute blast count ≥ 1,000 cell/microliter is sufficient to diagnose relapsed or refractory disease and facilitate confirmation of required genetic alterations for protocol therapy. 2. Refractory disease/induction failure:
Performance status: Participants must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1 or 2 (≥ 50% Lansky or Karnofsky score). Use ECOG for adult participants (≥18 to 21 years), Karnofsky for participants ≥16 to 18 years of age, and Lansky for participants \< 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.
Adequate organ function:
Prior therapy: Participants must have recovered from the acute toxic effects of all prior anti-cancer therapy (excluding Grade 2 toxicities that are not considered a safety risk or medically significant toxicity deemed irreversible by the Investigator) and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment.
Informed consent: Written, signed and dated informed consent and pediatric assent (if applicable) according to local law and legislation should be collected before start of any study procedures.
Female participants of childbearing potential must have a negative urine or serum pregnancy test confirmed prior to enrollment.
Female participants with infants must agree not to breastfeed their infants while on this study.
Contraception:
Enrollment APAL2020SC trial (US and Canada only): Participants in the US and Canada must have enrolled in the APAL2020SC trial prior to enrollment in the APAL2020K trial.
Exclusion
Participants who in the opinion of the investigator may not be able to comply with the study requirements of the study.
Participants with Down syndrome.
Participants with EMD are not eligible. EMD relapse is defined as biopsy proven extramedullary disease without bone marrow disease after documented CR following initial therapy.
Participants with isolated CNS relapse are not eligible, as well as symptomatic CNS3 disease.
Participants with acute promyelocytic leukemia (APL) or juvenile myelomonocytic leukemia (JMML).
Participants with malabsorption syndrome or any other condition that precludes enteral administration of a menin inhibitor.
Concomitant therapy: Gastric pH has great influence on absorption of ziftomenib; therefore, the use of proton pump inhibitors is prohibited, if necessary H2 Blockers may provide an alternative treatment option.
Participants who are currently receiving another investigational drug.
Participants with any known congenital bone marrow failure syndrome.
Participants with known prior allergy to any of the medications used in protocol therapy.
Participants with documented active, uncontrolled infection at the time of study entry.
Active/uncontrolled known human immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) and hepatitis C virus (HCV). Note: HIV testing does not need to be conducted at screening unless it is required per local guidelines or institutional standard.
Post menarche female participants with positive pregnancy test, and a lactating female participant.
Participant has a pre-existing disorder predisposing the participant to a serious or life-threatening infection (e.g., cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenia not related to the leukemia or its treatment).
Participants must not be receiving other investigational medications (defined as medicinal products not yet approved for any indications, including alternative/herbal therapies) within 30 days of first dose of study drug or while on study.
Significant congenital cardiovascular disease including, but not limited to conditions such as long QT syndrome, fundamental uncorrected cardiac defect (e.g., coarctation of the aorta) that poses a significant risk to the participant (ventricular septal defect or atrial septal defect are considered non-significant).
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 AEs.
For fludarabine and cytarabine: Hypersensitivity to the active substance or to any of the excipients.
Recent live vaccinations for at least 6 months.
What this trial measures
- Number of Participants Who Experience a Dose-limiting Toxicity (DLT)Day 1 to Day 49
- Area Under the Plasma Concentration-time Curve (AUC) of ZiftomenibCycle 1 Day 8: Pre-dose and 3, 8 and 24 hours post-dose. Cycle 1 Day 22: 0, 3, 8 and 24 hours post-dose (Cycle 1 is 49 days). Cycle 2: Any day pre-dose (Cycle 2 is 28 days).