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Relapsed/Refractory KMT2A-r Acute LeukemiaPhase 1NCT06376162

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

A Phase 1 study testing Ziftomenib, Cytarabine and Fludarabine in people with Relapsed/Refractory KMT2A-r Acute Leukemia and Relapsed/Refractory NUP98-r Acute Leukemia, run by PedAL BCU, LLC at 20 sites in 7 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial summary

The primary objective of the trial 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). Read more about this study

Who is it for?
Ages 0 to 21 years
What is being tested?
Ziftomenib, Cytarabine and Fludarabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
20 sitesin 7 countries
Study dates
18 Mar 2025to Mar 2033
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 0 to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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:
  • First or subsequent relapse:
  • Bone marrow relapse is defined as: a single bone marrow sample or bone biopsy showing ≥ 5% leukemic blasts by local morphology.
  • Participants with combined extramedullary and bone marrow relapse (defined as above), including central nervous system (CNS) disease, are eligible.
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  • Participants with asymptomatic CNS3 disease are eligible if they do not have isolated CNS3 extramedullary relapse.
  • Refractory disease/induction failure:
  • Acute myeloid leukemia (AML): The bone marrow contains ≥ 5% leukemic blasts by local morphology 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 ≥ 5% leukemic blasts by local morphology multiparameter flow cytometry at the end of induction and consolidation.
  • Performance status: Participants must have a performance status corresponding to Lansky or Karnofsky scores of ≥60. Use Karnofsky score for patients ≥16 years of age and Lansky score for patients <16 years of age. Patients 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 < 1.5x ULN unless increase is due to Gilbert's disease or leukemic involvement and ASAT or ALAT ≤ 3 x ULN unless considered due to leukemic involvement, in which case direct bilirubin < 3x ULN or ASAT and/or ALAT < 5x ULN will be considered eligible.
  • 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.
  • 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 confirmed by Sponsor's medical monitor) and must meet the following minimum duration from prior anti-cancer directed therapy prior to enrollment.
  • Cytotoxic chemotherapy: Must not have received within 14 days or within 5 drug half-lives (whichever is longer), of entry onto this trial, except for hydroxyurea or corticosteroids. Use of steroids and hydroxyurea for other purposes such as differentiation syndrome, or to premedication to prevent allergic reaction or during anesthesia is allowed.
  • Intrathecal cytotoxic therapy: No washout or waiting period is required for participants having received any combination of intrathecal cytarabine, methotrexate, and/or hydrocortisone.
  • Antibodies: ≥ 21 days must have elapsed from infusion of last dose of an antibody-drug conjugate. For unmodified antibodies or T cell engaging antibodies, 2 half-lives must have elapsed before enrollment. Any toxicity related to prior antibody therapy must be recovered back to baseline.
  • Interleukins, interferons and cytokines (other than hematopoietic growth factors): ≥ 21 days after the completion of interleukins, interferon or cytokines (other than hematopoietic growth factors).
  • Hematopoietic growth factors: ≥ 14 days after the last dose of a long-acting growth factor (e.g., peg-filgrastim) or 7 days for short-acting growth factor.
  • Radiation therapy (RT): 14 days have elapsed for local palliative RT (small port); ≥ 84 days must have elapsed if prior craniospinal RT or if ≥ 50% radiation of pelvis; ≥ 42 days must have elapsed if other substantial bone marrow (BM) radiation.
  • Stem cell infusions:
  • Participants who have relapsed after allogeneic (non-autologous) BM or stem cell transplant (with or without total body irradiation [TBI]) or boost infusion (any stem cell product; not including donor lymphocyte infusion [DLI]) must be at least 84 days post HSCT and without evidence of graft versus host disease (GVHD) of any severity except: the use of topical steroids for cutaneous GVHD is allowed and stable steroid doses less than or equal to 10 mg of prednisone daily is permitted. Prednisone dose must be adjusted for body surface area (BSA) in young children. Physiologic doses of hydrocortisone for participants with adrenal insufficiency is allowed.
  • Participants who after relapse and continue to receive cyclosporine, tacrolimus or other agents to treat or prevent either GVHD post BM transplant or organ rejection post-transplant are not eligible for this trial. In the relapse setting, participants must be off medications to treat or prevent either GVHD post BM transplant or organ rejection post-transplant for at least 14 days prior to enrollment. A stable steroid dose as mentioned above is allowed.
  • Cellular therapy: ≥ 30 days after the completion of DLI or any type of cellular Therapy (e.g., modified T cells, NK cells, dendritic cells, etc.).
  • Prior exposure to a different menin inhibitor: Participants who received previous treatment with a different menin inhibitor are allowed to enrol in the trial with the exception of those who experienced a severe adverse event attributable to the strong anti-proliferative/pro-differentiation effects of other menin inhibitors (such as severe differentiation syndrome). Participants who experienced a severe adverse event, which can directly be attributed to specific effects (e.g., long QT syndrome) observed with other menin inhibitors can participate in the trial if they fulfill the inclusion criteria. A washout period of 5x the drug half-life is required for prior menin inhibitors before 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 trial 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 trial.
  • Contraception:
  • Participants of reproductive potential, starting from menarche and onwards, may not participate unless they have agreed to use a highly effective contraceptive method per Clinical Trial Facilitation Group (CTFG) guidelines for the duration of trial therapy and for 6 months after the completion of all trial therapy. For further guidance please review the CTFG website.
  • Male participants must use a condom during intercourse and agree not to father a child or donate sperm during therapy and for the duration of trial therapy and for 4 months after the completion of all trial therapy.
  • 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.

Who cannot join

  • Participants who in the opinion of the investigator may not be able to comply with the trial requirements of the trial.
  • 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.
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  • 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 trial 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 trial drug or while on trial.
  • 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 trial 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.

Trial locations and contacts

20 sites in 7 countries. Contact the study team or a site near you to ask about taking part.

Dr. Branko Cuglievan contact

(713) 563-1499

bcuglievan@mdanderson.org

Dr. Sarah Tasian, MD contact

(215) 590-2299

tasians@chop.edu

20 sites in 7 countries

United States11 sites, 11 recruiting

  • Children's Healthcare of Atlanta

    Atlanta, Georgia, 30329

    Recruiting

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

    Recruiting

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

    Recruiting

  • Ann & Robert H. Lurie Children's Hospital of Chicago

    Chicago, Illinois, 60611

    Recruiting

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229-3026

    Recruiting

  • Texas Children's Hospital

    Houston, Texas, 77030

    Recruiting

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

    Recruiting

  • St. Jude Children's Research Hospital

    Memphis, Tennessee, 38105-3678

    Recruiting

  • Memorial Sloan Kettering Cancer Center - New York

    New York, New York, 10065

    Recruiting

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

    Recruiting

  • Seattle Children's Hospital

    Seattle, Washington, 98105

    Recruiting

Other trials in United States

France2 sites, 2 recruiting

  • CHU de Nantes - Hôpital Femme-Enfant-Adolescent

    Nantes, Loire-Atlantique, 44093

    Recruiting

  • CHU de Reims - Hôpital Robert Debré

    Paris, Île-de-France Region, 75019

    Recruiting

Other trials in France

Italy2 sites, 2 recruiting

  • Fondazione IRCCS San Gerardo dei Tintori (Ospedale San Gerardo)

    Monza, 20900

    Recruiting

  • Ospedale Pediatrico Bambino Gesù

    Roma, Rome, 00165

    Recruiting

Other trials in Italy

Spain2 sites, 2 recruiting

  • Hospital Universitari Vall d'Hebrón

    Barcelona, 08035

    Recruiting

  • Hospital Infantil Universitario Niño Jesús

    Madrid, 28009

    Recruiting

Other trials in Spain

Austria1 site, 1 recruiting

  • Sankt Anna-Kinderspital

    Vienna, State of Vienna, 1090

    Recruiting

Other trials in Austria

Canada1 site, 1 recruiting

  • SickKids - The Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

    Recruiting

Other trials in Canada

Netherlands1 site, 1 recruiting

  • Prinses Maxima Centrum Kinderoncologie

    Utrecht, 3584 CS

    Recruiting

Other trials in Netherlands

About this study

Official title: A Phase 1 Trial of Menin-inhibitor Ziftomenib in Combination With Chemotherapy for Children With Relapsed/Refractory KMT2A-r/NUP98-r/NPM1-m Acute Leukemia

The primary objective of the trial 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).

Being tested
Ziftomenib, Cytarabine, Fludarabine
Keywords
Ziftomenib, Acute leukemia, KMT2A-r, NUP98-r, NPM1-m
Medical subject headings
Recurrence

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT06376162
Study groupRoleWhat they receive
ZiftomenibExperimentalDuring Cycle 1 (49 days), participants will receive escalating doses of ziftomenib once daily (QD) on Days 8 to 49. Participants will also receive FLA chemotherapy consisting of fludarabine at a dose of 30 mg/m^2 (1 mg/kg/dose in infants <1 year of age or ≤10 kg) and cytarabine at a dose of 2000 mg/m^2 (67 mg/kg/dose in infants <1 year of age or ≤10 kg) QD on Day 1 to Day 5. Participants with <5% blasts will continue ziftomenib monotherapy until Day 49. Participants with a response and >5% blasts will continue to Cycle 2. During Cycle 2 (28 days), participants will receive escalating doses of ziftomenib QD on Day 1 to Day 28 in combination with FLA chemotherapy on Day 1 to Day 5. Participants who respond to treatment, but experience a delay prior to hematopoietic stem cell transplantation (HSCT), may receive up to 10 additional cycles (28 days) of ziftomenib monotherapy. Participants may also receive intrathecal therapy prophylaxis, if needed, during all cycles.
Receives: Drug: Ziftomenib; Drug: Cytarabine; Drug: Fludarabine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experience a Dose-limiting Toxicity (DLT)

    Measured: Day 1 to Day 49

  2. Area Under the Plasma Concentration-time Curve (AUC) of Ziftomenib

    Measured: Cycle 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).

Secondary outcomes (18)

  1. Number of Participants Who Experience an Adverse Event (AE)

    Including seriousness and relation to study therapy.

    Measured: Up to 1 month following the last administration of study drug (up to approximately 13 months)

  2. Number of AEs by Severity

    As graded using CTCAE version 5.0.

    Measured: Up to 1 month following the last administration of study drug (up to approximately 13 months)

  3. Maximum Observed Plasma Concentration (Cmax) of Ziftomenib

    Measured: Cycle 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).

  4. Minimum Observed Plasma Concentration (Cmin) of Ziftomenib

    Measured: Cycle 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).

  5. Time to Cmax (Tmax)

    Measured: Cycle 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).

  6. Truncated AUC (AUC0-t) of Ziftomenib in Combination with FLA Chemotherapy

    Measured: Cycle 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).

  7. Extrapolated AUC (AUC0-∞) of Ziftomenib in Combination with FLA Chemotherapy

    Measured: Cycle 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).

  8. Oral Plasma Clearance (CL/F) of Ziftomenib in Combination with FLA Chemotherapy

    Measured: Cycle 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).

  9. Volume of Distribution (Vz/F) of Ziftomenib in Combination with FLA Chemotherapy

    Measured: Cycle 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).

  10. Terminal Elimination Half-life (t1/2) of Ziftomenib in Combination with FLA Chemotherapy

    Measured: Cycle 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).

  11. HSCT Rate

    Calculated as the number of participants who receive a hematopoietic stem cell infusion divided by the total number of participants enrolled and started treatment.

    Measured: Up to 2 years

  12. Morphological Overall Response Rate (ORR)

    Measured: Up to 2 years

  13. Flow-based ORR

    Measured: Up to 2 years

  14. Flow-based Measurable Residual Disease (MRD) Negativity Rate

    Measured: Up to 2 years

  15. Duration of Response (DOR)

    Measured: Up to 2 years

  16. Event-free Survival (EFS)

    Measured: Up to 2 years

  17. Overall Survival (OS)

    Measured: Up to 2 years

  18. Cumulative Incidence of Relapse (CIR)

    Measured: Up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Apr 2024
  2. Study start18 Mar 2025
  3. Primary completionMar 2033 (estimated)
  4. Study completionMar 2033 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06376162
Sponsor's protocol ID
ITCC-101/APAL2020K
Other IDs
2023-505262-28-00, 2023
Status last verified
Oct 2026
First submitted
28 Mar 2024
Last updated
9 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Ziftomenib, Cytarabine and Fludarabine in people with Relapsed/Refractory KMT2A-r Acute Leukemia and Relapsed/Refractory NUP98-r Acute Leukemia, run by PedAL BCU, LLC at 20 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 36 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 9 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in United States, France, Italy, Spain, Austria and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Dr. Branko Cuglievan ((713) 563-1499, bcuglievan@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experience a Dose-limiting Toxicity (DLT) (time frame: Day 1 to Day 49). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06376162.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Oct 2026.

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