Promising new combo targets Hard-to-Treat infant leukemia
NCT ID NCT05761171
First seen Jun 27, 2026 · Last updated Aug 26, 2026 · Updated 4 times
Summary
This study tests a new oral drug (revumenib) combined with standard chemotherapy for infants and young children with a specific type of leukemia (KMT2A-rearranged) that has returned or not responded to treatment. The goal is to see if the combination is safe and works better than current options. About 78 children aged 1 month to under 6 years will take part.
This is an AI summary of the original study and may miss details. Read our disclaimer.
Study facts
What this study's own registry entry says, in plain language.
- Phase
-
Phase 2
Tests whether the treatment actually works, and watches for side effects, in a larger group.
- Participants
-
About 78 people
The number the study aims to enrol. It can still change while the study runs.
- Started
-
Jan 2024
- Expected to finish
-
Dec 2027
An estimate. End dates often move.
- Lead sponsor
-
A research network
The lead sponsor is a research network or cooperative group.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
-
1 month to 6 years
- Sex
-
Anyone
- Healthy volunteers
-
Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
Inclusion Criteria: * Patients must be 1 month to \< 6 years old at the time of study enrollment and must have had initial diagnosis of leukemia at \< 2 years old. * Patients must have KMT2A-rearranged acute lymphoblastic leukemia (ALL), acute leukemia of ambiguous lineage (ALAL), or mixed phenotype acute leukemia (MPAL), which is determined to be refractory or in first marrow relapse. Patients who have experienced lineage switch to acute myeloid leukemia (AML) are eligible assuming documented prior diagnosis of KMT2A-rearranged ALL/ALAL/MPAL. All patients must undergo cytogenetics and fluorescence in situ hybridization (FISH) testing of a relapsed/refractory blast sample at a Children's Oncology Group (COG)-approved laboratory for KMT2A-R status determination and the presence of a KMT2A- rearrangement must be confirmed by central review. Cytogenetics results must be submitted for central review by Day 10 of protocol therapy, for confirmation of KMT2A-R status. Patients enrolled with refractory disease may utilize initial diagnostic cytogenetics for eligibility and submission for central review if testing was performed at a COG approved laboratory. Patients will be eligible to remain on protocol therapy if KMT2A-R is confirmed by central review. Additional methods of assessing for KMT2A-R may be considered if FISH does not detect the rearrangement. * Disease status at time of enrollment must be one of the following: * First relapse (untreated): Any recurrence of marrow disease, with or without other extramedullary sites(s), at any point after achieving remission ("remission-1", per definition below) and meeting one of the below criteria. Patients must not have received any disease-directed therapy for the marrow relapse prior to enrollment, other than permitted cytoreduction. * Relapse M1: M1 morphology (\< 5% blasts) + at least 2 confirmatory tests showing \>= 1% blasts (testing includes flow, cytogenetics, polymerase chain reaction \[PCR\]/next-generation sequencing \[NGS\] of immunoglobulin \[Ig\]/T-cell receptor \[TCR\] rearrangement, and/or PCR or NGS of fusion gene identical to diagnosis), OR * Relapse M2: M2 morphology (5-25% blasts) + 1 confirmatory test showing \> 1% blasts, OR * Relapse M3: M3 morphology (\> 25% blasts) * Primary refractory, or failure to achieve remission-1: remission-1 is defined as \< 1% marrow blasts by flow MRD and resolution of extramedullary disease following at least 2 courses of frontline chemotherapy. Patients who receive 2 courses of chemotherapy and 1 course of blinatumomab are also eligible, but no further treatment attempts beyond that are permitted * Central nervous system (CNS) disease: Patients must have CNS1 or CNS2 status and no clinical signs or neurologic symptoms suggestive of CNS leukemia, such as cranial palsy. * Patients with CNS3 disease may receive antecedent intrathecal chemotherapy to achieve CNS1 or CNS2 status prior to enrollment. * Patients with a history of CNS chloromatous disease are required to have no radiographic evidence of CNS disease prior to enrollment. * White blood cell (WBC) must be \< 50,000/uL at the time of study enrollment. Patients can receive cytoreduction with hydroxyurea and/or corticosteroids for up to 7 days prior to enrollment. * Patients \>= 12 months of age must have a performance status by Lansky Scale of \>= 50%. * Patients must be able to take enteral medications. Acceptable routes of administration for revumenib (SNDX-5613) include: oral (PO), nasogastric (NG) tube, nasojejunal (NJ) tube, nasoduodenal (ND), and gastrostomy tube (G-tube). * Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study * Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive: * \>= 14 days must have elapsed after the completion of other cytotoxic therapy, including patients who relapse during pre-Maintenance upfront therapy, with these specific exceptions: cytoreduction with hydroxyurea and/or corticosteroids, and intrathecal chemotherapy, which have no required washout periods. For patients who relapse during upfront Maintenance therapy, \>= 7 days must have elapsed after the last dose of chemotherapy. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy. * NOTE: Cytoreduction with hydroxyurea and/or corticosteroids is permitted prior to enrollment for patients with WBC \>= 50,000/uL, and by provider discretion regardless of WBC, to reduce potential risk of differentiation syndrome with revumenib initiation. Hydroxyurea and/or corticosteroids may be given for up to 7 days, with no wash-out required. * NOTE: No waiting period is required for patients having received intrathecal cytarabine, methotrexate, and/or hydrocortisone. Intrathecal chemotherapy that is given up to 7 days prior to the initiation of protocol therapy counts as protocol therapy and not prior anti-cancer therapy. Intrathecal chemotherapy given \> 7 days prior does not count as protocol therapy. * NOTE: Prior exposure to fludarabine and cytarabine (FLA) is permitted. * Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count \[ANC\] counts): \>= 7 days after the last dose of agent. * Antibodies: \>= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =\< 1. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria. * Hematopoietic growth factors: \>= 14 days after the last dose of a long-acting growth factor (e.g., pegfilgrastim) or \>= 7 days for short-acting growth factor. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator. * Interleukins, interferons and cytokines (other than hematopoietic growth factors): \>= 21 days after the completion of interleukins, interferon, or cytokines * Stem cell infusions (with or without total body irradiation \[TBI\]): * Allogeneic (non-autologous) bone marrow or stem cell transplant, or stem cell boost: \>= 84 days after infusion * Donor leukocyte infusion: \>= 28 days * Cellular therapy: \>= 28 days after the completion of any type of cellular therapy (e.g., modified T cells, natural killer \[NK\] cells, dendritic cells, etc.) * Radiation therapy (XRT)/external beam irradiation including protons: \>= 14 days after local XRT; \>= 84 days after TBI, craniospinal XRT or if radiation to \>= 50% of the pelvis; \>= 42 days if other substantial bone marrow radiation. * A creatinine based on age as follows: * Age 1 month to \< 6 months: maximum creatinine 0.4 mg/dL * Age 6 months to \< 1 year: maximum creatinine 0.5 mg/dL * Age 1 to \< 2 years: maximum creatinine 0.6 mg/dL * Age 2 to \< 6 years: maximum creatinine 0.8 mg/dL OR * A 24-hour urine creatinine clearance \>= 70 mL/min/1.73 m\^2 OR * A glomerular filtration rate (GFR) \>= 70 mL/min/1.73 m\^2. GFR must be performed using direct measurement with a nuclear blood sampling method OR direct small molecule clearance method (iothalamate or other molecule per institutional standard). * NOTE: Estimated GFR (eGFR) from creatinine, cystatin C or other estimates are not acceptable for determining eligibility. * A direct bilirubin =\< 1.5 x upper limit of normal (ULN) for age, unless disease related * Serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) =\< 135 U/L (3 x ULN) unless disease related. * Note: For the purpose of eligibility, the ULN for SGPT (ALT) has been set to the value of 45 U/L * Shortening fraction of \>= 27% by echocardiogram, or ejection fraction of \>= 50% by radionuclide angiogram. * Corrected QT interval using Fridericia formula (QTcF) of \< 450 msec (using the average of triplicate measurements) * NOTE: There are no specific electrolyte parameters for eligibility. However, it should be noted that, to limit QTc prolongation risk, patients must maintain adequate potassium and magnesium levels to initiate and continue revumenib (SNDX-5613) on protocol therapy. * Patients must be able to comply with the safety monitoring requirements of the study, in the opinion of the treating investigator. Exclusion Criteria: * Patients with isolated extramedullary leukemia. * Patients diagnosed with Down syndrome. * Patients known to have one of the following syndromes: * Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known bone marrow failure syndrome. * Patients with a secondary KMT2A-R leukemia that developed after treatment of prior malignancy with cytotoxic chemotherapy. * Patients with a history of congenital prolonged QT syndrome, congestive heart failure or uncontrolled arrhythmia in the past 6 months prior to study enrollment. * Patients with an active, uncontrolled infection, further defined below: * Positive bacterial blood culture within 48 hours of study enrollment * Fever above 38.2 degrees Celsius (C) within 48 hours of study enrollment with clinical signs of infection. Fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability * A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection * Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved. For patients with Clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline * Active viral or protozoal infection requiring IV treatment * Human immunodeficiency virus (HIV)-infected patients are eligible if on effective anti-retroviral therapy that does not interact with planned study agents and with undetectable viral load within 6 months of enrollment. * Patients with active acute graft-versus-host disease (GVHD) \> grade 0 (unless skin only), or chronic GVHD \> mild (unless skin only) are not eligible. Patients with acute or chronic skin GVHD that is =\< grade 1, or chronic skin GVHD that is graded as mild are eligible. * Patients who have received a prior solid organ transplantation. * Patients with known Charcot-Marie-Tooth disease, if treating on Regimen A (with vincristine). * CYP3A4 Inhibitors or Inducers: Strong CYP3A4 inhibitors or moderate or strong CYP3A4 inducers are prohibited during treatment, with the exception of strong CYP3A4 inhibitor -azoles during monotherapy cycles. These agents should be discontinued at least 5 half-lives prior to starting protocol therapy. Concomitant use of a strong CYP3A4 inhibitor -azole antifungal is permitted during the revumenib (SNDX-5613) monotherapy cycles, with appropriate revumenib (SNDX-5613) dose modification. * P-glycoprotein (P-gp) inhibitors or inducers: Vincristine is a substrate for P-gp. Concomitant use of P-gp inhibitors or inducers with vincristine (patients receiving Regimen A Cycle 1) should be avoided. * Investigational drugs: Patients who are currently receiving another investigational drug. * Anti-cancer agents: Patients who are currently receiving other anti-cancer agents (exceptions: hydroxyurea and corticosteroids, which may be used as cytoreduction prior to enrollment). * Anti-GVHD agents: Patients who are receiving cyclosporine, tacrolimus, or other systemic agents to treat graft-versus-host disease post bone marrow transplant. Patients should discontinue anti-GVHD agents \> 7 days prior to enrollment and have no evidence of worsening GVHD. Topical steroids are permitted. * Patients who have previously been treated with revumenib (SNDX-5613). Prior exposure to other menin inhibitors is permitted. * All patients and/or their parents or legal guardians must sign a written informed consent. * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met.
Get updates
Get notified about this study
Sign up to get updates when this study changes or when new studies for KMT2A-rearranged acute leukemia of ambiguous lineage are added.
Genom att skicka in godkänner du våra Användarvillkor
Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
Contacts and locations
Locations
-
AdventHealth Orlando
Orlando, Florida, 32803, United States
-
Albany Medical Center
Albany, New York, 12208, United States
-
Alfred I duPont Hospital for Children
Wilmington, Delaware, 19803, United States
-
Alliance for Childhood Diseases/Cure 4 the Kids Foundation
Las Vegas, Nevada, 89135, United States
-
Arkansas Children's Hospital
Little Rock, Arkansas, 72202-3591, United States
-
Arnold Palmer Hospital for Children
Orlando, Florida, 32806, United States
-
BI-LO Charities Children's Cancer Center
Greenville, South Carolina, 29605, United States
-
Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center
Houston, Texas, 77030, United States
-
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4, Canada
-
Bronson Methodist Hospital
Kalamazoo, Michigan, 49007, United States
-
C S Mott Children's Hospital
Ann Arbor, Michigan, 48109, United States
-
CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)
Québec, G1V 4G2, Canada
-
CancerCare Manitoba
Winnipeg, Manitoba, R3E 0V9, Canada
-
Centre Hospitalier Universitaire Sainte-Justine
Montreal, Quebec, H3T 1C5, Canada
-
Children's Healthcare of Atlanta - Arthur M Blank Hospital
Atlanta, Georgia, 30329, United States
-
Children's Hospital
London, Ontario, N6A 5W9, Canada
-
Children's Hospital Colorado
Aurora, Colorado, 80045, United States
-
Children's Hospital Medical Center of Akron
Akron, Ohio, 44308, United States
-
Children's Hospital and Medical Center of Omaha
Omaha, Nebraska, 68114, United States
-
Children's Hospital of Alabama
Birmingham, Alabama, 35233, United States
-
Children's Hospital of Eastern Ontario
Ottawa, Ontario, K1H 8L1, Canada
-
Children's Hospital of Michigan
Detroit, Michigan, 48201, United States
-
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104, United States
-
Children's Hospital of Pittsburgh of UPMC
Pittsburgh, Pennsylvania, 15224, United States
-
Children's Hospital of San Antonio
San Antonio, Texas, 78207, United States
-
Children's Hospital of The King's Daughters
Norfolk, Virginia, 23507, United States
-
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
-
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
-
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229, United States
-
Connecticut Children's Medical Center
Hartford, Connecticut, 06106, United States
-
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
-
Dayton Children's Hospital
Dayton, Ohio, 45404, United States
-
Dell Children's Medical Center of Central Texas
Austin, Texas, 78723, United States
-
Geisinger Medical Center
Danville, Pennsylvania, 17822, United States
-
Golisano Children's Hospital of Southwest Florida
Fort Myers, Florida, 33908, United States
-
Hackensack University Medical Center
Hackensack, New Jersey, 07601, United States
-
Hospital for Sick Children
Toronto, Ontario, M5G 1X8, Canada
-
IWK Health Centre
Halifax, Nova Scotia, B3K 6R8, Canada
-
Johns Hopkins University/Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287, United States
-
Kaiser Permanente Downey Medical Center
Downey, California, 90242, United States
-
Kaiser Permanente-Oakland
Oakland, California, 94611, United States
-
Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York, 10016, United States
-
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227, United States
-
Loma Linda University Medical Center
Loma Linda, California, 92354, United States
-
Lurie Children's Hospital-Chicago
Chicago, Illinois, 60611, United States
-
McMaster Children's Hospital at Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5, Canada
-
Medical City Dallas Hospital
Dallas, Texas, 75230, United States
-
Memorial Regional Hospital/Joe DiMaggio Children's Hospital
Hollywood, Florida, 33021, United States
-
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
-
Mercy Hospital Saint Louis
St Louis, Missouri, 63141, United States
-
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
-
Nemours Children's Hospital
Orlando, Florida, 32827, United States
-
Newark Beth Israel Medical Center
Newark, New Jersey, 07112, United States
-
Nicklaus Children's Hospital
Miami, Florida, 33155, United States
-
Oregon Health and Science University
Portland, Oregon, 97239, United States
-
Prisma Health Richland Hospital
Columbia, South Carolina, 29203, United States
-
Renown Regional Medical Center
Reno, Nevada, 89502, United States
-
Riley Hospital for Children
Indianapolis, Indiana, 46202, United States
-
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
-
Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital
New Brunswick, New Jersey, 08903, United States
-
Saint Christopher's Hospital for Children
Philadelphia, Pennsylvania, 19134, United States
-
Saint Joseph's Hospital/Children's Hospital-Tampa
Tampa, Florida, 33607, United States
-
Saint Jude Children's Research Hospital
Memphis, Tennessee, 38105, United States
-
Sanford Broadway Medical Center
Fargo, North Dakota, 58122, United States
-
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota, 57117-5134, United States
-
Seattle Children's Hospital
Seattle, Washington, 98105, United States
-
State University of New York Upstate Medical University
Syracuse, New York, 13210, United States
-
The Children's Hospital at TriStar Centennial
Nashville, Tennessee, 37203, United States
-
UCSF Benioff Children's Hospital Oakland
Oakland, California, 94609, United States
-
UCSF Medical Center-Mission Bay
San Francisco, California, 94158, United States
-
UF Health Cancer Institute - Gainesville
Gainesville, Florida, 32610, United States
-
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599, United States
-
UT MD Anderson Cancer Center
Houston, Texas, 77030, United States
-
UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas, 75390, United States
-
University of Chicago Comprehensive Cancer Center
Chicago, Illinois, 60637, United States
-
University of Iowa/Holden Comprehensive Cancer Center
Iowa City, Iowa, 52242, United States
-
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, 40536, United States
-
University of Minnesota/Masonic Cancer Center
Minneapolis, Minnesota, 55455, United States
-
University of Mississippi Medical Center
Jackson, Mississippi, 39216, United States
-
University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
-
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106, United States
-
University of Virginia Cancer Center
Charlottesville, Virginia, 22908, United States
-
Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee, 37232, United States
-
Washington University School of Medicine
St Louis, Missouri, 63110, United States
More trials for these conditions
Other studies related to the condition(s) this trial covers.
- Engineered immune cells aim to wipe out stubborn leukemia
- Engineered immune cells take aim at tough childhood leukemia
- New combo aims to wipe out hidden leukemia cells
- Selective immune cell removal may tame transplant complications
- Triple-Target CAR T-Cells offer new hope for tough blood cancers
- New drug cocktail shows promise for Hard-to-Treat leukemia