Ziftomenib in Combination With Chemotherapy for Children With Relapsed/Refractory Acute Leukemia

Recruiting now · Phase 1

Conditions studied: Relapsed/Refractory KMT2A-r Acute Leukemia, Relapsed/Refractory NUP98-r Acute Leukemia, Relapsed/Refractory NPM1-m Acute Leukemia

In brief

The primary objective of the study is to determine the recommended phase 2 dose (RP2D) of ziftomenib in combination with chemotherapy (FLA) in children with relapsed or refractory KMT2A-r, NUP98-r, or NPM1-m acute leukemia based on safety and pharmacokinetics (PK).

Key facts

Study ID: NCT06376162
Run by: PedAL BCU, LLC
People needed: 20
Starts: 2025-03-18
Expected to finish: 2027-01-01
Last updated by the study team: 2025-10-20

Who can join

Age: any, up to 21. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

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:
Bone marrow relapse is defined as:
A single bone marrow sample showing ≥ 5% leukemic blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing, or other molecular method.
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.
Participants with combined extramedullary and bone marrow relapse (defined as above) are eligible.
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.
Participants with asymptomatic CNS3 disease are eligible if they do not have isolated CNS3 extramedullary relapse.
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.
Refractory disease/induction failure:
Acute myeloid leukemia (AML): The bone marrow contains ≥ 1% leukemic blasts by MFC at the end of 2 cycles of induction therapy.
Acute lymphoblastic leukemia (ALL)/mixed-phenotype acute leukemia (MPAL)/acute undifferentiated leukemia (AUL): The bone marrow contains ≥ 1% leukemic blasts by MFC at the end of induction and consolidation, or persistent MRD prior HSCT (defined as > 0.01%).
For participants unable to have bone marrow assessed, a peripheral blood absolute blast count ≥ 1,000 cell/microliter is sufficient to diagnose relapsed or refractory disease.
Molecular refractory disease in infant ALL, defined as MRD >0.05% after primary induction and consolidation therapy measured by MFC or PCR.
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:
Renal function defined as: Creatinine clearance (CrCl) ≥60 mL/min (as measured by a nuclear glomerular filtration rate [GFR] scan or calculated by the Schwartz formula and normalized to a body surface area of 1.73 m\^2).
Liver function defined as:
Direct bilirubin < 3 x upper limit of normal (ULN) and Serum glutamic pyruvic transaminase (SGPT) (alanine transaminase [ALT]) ≤ 5 x ULN.
If liver abnormality is due to radiographically identifiable leukemia infiltrate, the participant will remain eligible.
Cardiac function defined as: Pre-treatment left ventricular function on echocardiography: Fractional shortening (FS) ≥ 25% or ejection fraction (EF) ≥ 40%, and no signs of congestive heart failure within 4 weeks before start of screening.

You may not qualify if…

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.

Where it is running

Children's Hospital Los Angeles — Los Angeles, California, United States (enrolling)
Children's Hospital Colorado — Aurora, Colorado, United States (enrolling)
Children's Healthcare of Atlanta — Atlanta, Georgia, United States (enrolling)
Ann & Robert H. Lurie Children's Hospital of Chicago — Chicago, Illinois, United States (enrolling)
Dana-Farber Cancer Institute — Boston, Massachusetts, United States (enrolling)
Memorial Sloan Kettering Cancer Center - New York — New York, New York, United States (enrolling)
Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States (enrolling)
Children's Hospital of Philadelphia — Philadelphia, Pennsylvania, United States (enrolling)
St. Jude Children's Research Hospital — Memphis, Tennessee, United States (enrolling)
Texas Children's Hospital — Houston, Texas, United States (enrolling)
Seattle Children's Hospital — Seattle, Washington, United States (enrolling)
Sankt Anna-Kinderspital — Vienna, State of Vienna, Austria (enrolling)
SickKids - The Hospital for Sick Children — Toronto, Ontario, Canada (enrolling)
CHU de Nantes - Hôpital Femme-Enfant-Adolescent — Nantes, Loire-Atlantique, France (enrolling)
CHU de Reims - Hôpital Robert Debré — Paris, Île-de-France Region, France (enrolling)
Ospedale Pediatrico Bambino Gesù — Roma, Rome, Italy (enrolling)
Fondazione IRCCS San Gerardo dei Tintori (Ospedale San Gerardo) — Monza, Italy (enrolling)
Prinses Maxima Centrum Kinderoncologie — Utrecht, Netherlands (enrolling)
Hospital Universitari Vall d'Hebrón — Barcelona, Spain (enrolling)
Hospital Infantil Universitario Niño Jesús — Madrid, Spain (enrolling)

Full record on ClinicalTrials.gov

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