Clinical trial for Relapsed/Refractory KMT2A-r Acute Leukemia
Official title Ziftomenib in Combination With Chemotherapy for Children With Relapsed/Refractory Acute Leukemia
ClinicalTrials.gov ID: NCT06376162
What this study is testing
What is Ziftomenib?
An investigational oral capsule being studied as a potential treatment for relapsed or refractory KMT2A‑r acute leukemia in children. It is designed to inhibit the menin protein, which may disrupt abnormal gene signaling in leukemia cells.
Plain-language explanation of the investigational treatment. It is being studied and is not an approved or proven therapy. The study team can confirm the details.
- What it's testing
- The study aims to find the safest and most effective dose of ziftomenib when given with chemotherapy, based on safety and how the drug behaves in the body.
- Who it's for
- Children with relapsed or refractory KMT2A‑r, NUP98‑r, or NPM1‑m acute leukemia.
- What's involved
- Participants will receive ziftomenib together with standard chemotherapy and will have regular safety checks and blood tests to measure drug levels.
- Time commitment
- Treatment follows the chemotherapy schedule with regular clinic visits for monitoring during the study period.
- Phase 1: an early, usually small safety study
A plain-language read of the study's public ClinicalTrials.gov listing. The study team confirms the details.
Who can take part
Ages 0 to 21
You may be able to join 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...
- 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.
- Participants with asymptomatic CNS3 disease are eligible if they do not have isolated CNS3 extramedullary relapse.
You likely can't join if
- 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...
- 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.
See the full eligibility criteria
Who can 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).
- 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.
- Participants with asymptomatic CNS3 disease are eligible if they do not have isolated CNS3 extramedullary relapse.
- 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...
- 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.
- 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).
- 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...
- 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...
- 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...
- 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.
- 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.
- 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
- 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
- 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.
- 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...
- 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.
- 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)...
- 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.
What rules you out
- 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.
- 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).
- 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...
- 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...
- 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...
- 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.
The study team makes the final eligibility decision.
Where it is enrolling
- Los Angeles, California, United States
- Aurora, Colorado, United States
- Atlanta, Georgia, United States
- Chicago, Illinois, United States
- Boston, Massachusetts, United States
- New York, New York, United States
- Cincinnati, Ohio, United States
- Philadelphia, Pennsylvania, United States
- Memphis, Tennessee, United States
- Houston, Texas, United States
- Seattle, Washington, United States
- Vienna, State of Vienna, Austria
- Toronto, Ontario, Canada
- Nantes, Loire-Atlantique, France
- Paris, Île-de-France Region, France
- Roma, Rome, Italy
- Monza, Italy
- Utrecht, Netherlands
- Barcelona, Spain
- Madrid, Spain
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, but 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, 0 years to 21 years. The study team makes the final eligibility decision.
Where is this trial taking place?
This study is enrolling now at Los Angeles, California, United States; Aurora, Colorado, United States; Atlanta, Georgia, United States; Chicago, Illinois, United States; Boston, Massachusetts, United States; New York, New York, United States and 14 more locations. Enter your location above to see the nearest enrolling site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool that is independent of the study sponsor. Details come from ClinicalTrials.gov. The study team decides eligibility, and your own doctor gives medical advice.