AzTrials
AzTrials

Recurrent Acute Leukemia of Ambiguous LineagePhase 2NCT05761171

A Study of Revumenib in Combination With Chemotherapy for Patients Diagnosed With Relapsed or Refractory Leukemia

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Calaspargase Pegol in people with Recurrent Acute Leukemia of Ambiguous Lineage and Recurrent Acute Lymphoblastic Leukemia, run by Children's Oncology Group at 84 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This phase II trial tests the safety and best dose of revumenib in combination with chemotherapy, and evaluates whether this treatment improves the outcome in infants and young children who have leukemia that has come back (relapsed) or does not respond to treatment (refractory) and is associated with a KMT2A (MLL)… Read more about this study

Who is it for?
Ages 1 month to 6 years
What is being tested?
Biospecimen Collection, Bone Marrow Aspiration and Calaspargase Pegol
Could I receive a placebo?
No, everyone receives an active treatment
How many people
78 participants
Where
84 sitesin 2 countries
Study dates
8 Jan 2024to 31 Dec 2027
Phase
Phase 2
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 1 month to 6 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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
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  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

84 sites in 2 countries.

84 sites in 2 countries

United States75 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • Albany Medical Center

    Albany, New York, 12208

  • University of New Mexico Cancer Center

    Albuquerque, New Mexico, 87106

  • C S Mott Children's Hospital

    Ann Arbor, Michigan, 48109

  • Children's Healthcare of Atlanta - Arthur M Blank Hospital

    Atlanta, Georgia, 30329

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Dell Children's Medical Center of Central Texas

    Austin, Texas, 78723

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Children's Hospital of Alabama

    Birmingham, Alabama, 35233

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Lurie Children's Hospital-Chicago

    Chicago, Illinois, 60611

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Cincinnati Children's Hospital Medical Center

    Cincinnati, Ohio, 45229

  • Prisma Health Richland Hospital

    Columbia, South Carolina, 29203

  • Nationwide Children's Hospital

    Columbus, Ohio, 43205

  • Medical City Dallas Hospital

    Dallas, Texas, 75230

  • UT Southwestern/Simmons Cancer Center-Dallas

    Dallas, Texas, 75390

  • Geisinger Medical Center

    Danville, Pennsylvania, 17822

  • Dayton Children's Hospital

    Dayton, Ohio, 45404

  • Children's Hospital of Michigan

    Detroit, Michigan, 48201

  • Kaiser Permanente Downey Medical Center

    Downey, California, 90242

  • Sanford Broadway Medical Center

    Fargo, North Dakota, 58122

  • Golisano Children's Hospital of Southwest Florida

    Fort Myers, Florida, 33908

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • BI-LO Charities Children's Cancer Center

    Greenville, South Carolina, 29605

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Connecticut Children's Medical Center

    Hartford, Connecticut, 06106

  • Memorial Regional Hospital/Joe DiMaggio Children's Hospital

    Hollywood, Florida, 33021

  • Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

    Houston, Texas, 77030

  • UT MD Anderson Cancer Center

    Houston, Texas, 77030

  • Riley Hospital for Children

    Indianapolis, Indiana, 46202

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Bronson Methodist Hospital

    Kalamazoo, Michigan, 49007

  • Children's Mercy Hospitals and Clinics

    Kansas City, Missouri, 64108

  • Alliance for Childhood Diseases/Cure 4 the Kids Foundation

    Las Vegas, Nevada, 89135

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Arkansas Children's Hospital

    Little Rock, Arkansas, 72202-3591

  • Loma Linda University Medical Center

    Loma Linda, California, 92354

  • Saint Jude Children's Research Hospital

    Memphis, Tennessee, 38105

  • Nicklaus Children's Hospital

    Miami, Florida, 33155

  • University of Minnesota/Masonic Cancer Center

    Minneapolis, Minnesota, 55455

  • The Children's Hospital at TriStar Centennial

    Nashville, Tennessee, 37203

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

    New Brunswick, New Jersey, 08903

  • Laura and Isaac Perlmutter Cancer Center at NYU Langone

    New York, New York, 10016

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Newark Beth Israel Medical Center

    Newark, New Jersey, 07112

  • Children's Hospital of The King's Daughters

    Norfolk, Virginia, 23507

  • UCSF Benioff Children's Hospital Oakland

    Oakland, California, 94609

  • Kaiser Permanente-Oakland

    Oakland, California, 94611

  • Children's Hospital and Medical Center of Omaha

    Omaha, Nebraska, 68114

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

  • AdventHealth Orlando

    Orlando, Florida, 32803

  • Arnold Palmer Hospital for Children

    Orlando, Florida, 32806

  • Nemours Children's Hospital

    Orlando, Florida, 32827

  • Children's Hospital of Philadelphia

    Philadelphia, Pennsylvania, 19104

  • Saint Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134

  • Children's Hospital of Pittsburgh of UPMC

    Pittsburgh, Pennsylvania, 15224

  • Legacy Emanuel Children's Hospital

    Portland, Oregon, 97227

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Renown Regional Medical Center

    Reno, Nevada, 89502

  • Children's Hospital of San Antonio

    San Antonio, Texas, 78207

  • UCSF Medical Center-Mission Bay

    San Francisco, California, 94158

  • Seattle Children's Hospital

    Seattle, Washington, 98105

  • Sanford USD Medical Center - Sioux Falls

    Sioux Falls, South Dakota, 57117-5134

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • Saint Joseph's Hospital/Children's Hospital-Tampa

    Tampa, Florida, 33607

  • Children's National Medical Center

    Washington D.C., District of Columbia, 20010

  • Alfred I duPont Hospital for Children

    Wilmington, Delaware, 19803

Other trials in United States

Canada9 sites

  • IWK Health Centre

    Halifax, Nova Scotia, B3K 6R8

  • McMaster Children's Hospital at Hamilton Health Sciences

    Hamilton, Ontario, L8N 3Z5

  • Children's Hospital

    London, Ontario, N6A 5W9

  • Centre Hospitalier Universitaire Sainte-Justine

    Montreal, Quebec, H3T 1C5

  • Children's Hospital of Eastern Ontario

    Ottawa, Ontario, K1H 8L1

  • CHU de Quebec-Centre Hospitalier de l'Universite Laval (CHUL)

    Québec, G1V 4G2

  • Hospital for Sick Children

    Toronto, Ontario, M5G 1X8

  • British Columbia Children's Hospital

    Vancouver, British Columbia, V6H 3V4

  • CancerCare Manitoba

    Winnipeg, Manitoba, R3E 0V9

Other trials in Canada

About this study

Official title: A Phase 2 Study of SNDX-5613 in Combination With Chemotherapy for Patients With Relapsed or Refractory KMT2A-Rearranged Infant Leukemia

This phase II trial tests the safety and best dose of revumenib in combination with chemotherapy, and evaluates whether this treatment improves the outcome in infants and young children who have leukemia that has come back (relapsed) or does not respond to treatment (refractory) and is associated with a KMT2A (MLL) gene rearrangement (KMT2A-R). Leukemia is a cancer of the white blood cells, where too many underdeveloped (abnormal) white blood cells, called "blasts", are found in the bone marrow, which is the soft, spongy center of the bones that produces the three major blood cells: white blood cells to fight infection; red blood cells that carry oxygen; and platelets that help blood clot and stop bleeding. The blasts crowd out the normal blood cells in the bone marrow and spread to the blood. They can also spread to the brain, spinal cord, and/or other organs of the body. The leukemia cells of some children have a genetic change in which a gene (KMT2A) is broken and combined with other genes that typically do not interact with one another; this is called "rearranged". This genetic rearrangement alters how other genes are turned on or off in the cell, turning on genes that drive the development of leukemia. Patients with KMT2A rearrangement have higher risk for cancer coming back after treatment. Revumenib is an oral medicine that directly targets the changes that occur in a cell with a KMT2A rearrangement and has been shown to specifically kill these leukemia cells in preclinical laboratory settings and in animals. Drugs used in chemotherapy, such as vincristine, prednisone, asparaginase, fludarabine and cytarabine work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial is being done to find out if the combination of revumenib and chemotherapy would be safe and/or effective in treating infants and young children with relapsed or refractory KMT2A-R leukemia.

Read the detailed description

PRIMARY OBJECTIVES:

  1. To determine the recommended phase 2 dose (RP2D) of revumenib administered in combination with chemotherapy in patients with relapsed or refractory (R/R) KMT2A-rearranged (KMT2A-R) acute lymphoblastic leukemia (ALL).

II. To estimate the minimal residual disease (MRD) negative remission rate of patients age >= 6 months at enrollment with R/R infant KMT2A-R ALL treated with revumenib in combination with chemotherapy.

SECONDARY OBJECTIVES:

  1. To characterize the pharmacokinetics (PK) of revumenib administered with chemotherapy in patients with R/R infant KMT2A-R ALL.

II. To estimate the 18-month event-free survival (EFS) of patients with R/R infant KMT2A-R ALL treated with revumenib in combination with chemotherapy.

III. To estimate 18-month overall survival (OS) of patients with R/R infant KMT2A-R ALL treated with revumenib in combination with chemotherapy.

IV. To characterize the tolerability of revumenib given as monotherapy in patients with R/R infant KMT2A-R ALL.

EXPLORATORY OBJECTIVES:

  1. To assess the biologic activity of revumenib administered with chemotherapy in patients with R/R KMT2A-R ALL.

II. To estimate the MRD negative remission rate of patients with R/R non-infant KMT2A-R ALL treated with revumenib in combination with chemotherapy.

III. To characterize the PK of calaspargase pegol and describe associated toxicities for patients with R/R KMT2A-R ALL.

IV. To describe the anti-cancer therapies received before and after administration of revumenib by patients with R/R KMT2A-R ALL.

  1. To describe the MRD negative remission rate of patients age < 6 months at enrollment with R/R infant KMT2A-R ALL treated with revumenib in combination with chemotherapy.

OUTLINE: Patients with acute lymphoblastic leukemia (ALL), acute leukemia of ambiguous lineage (ALAL), or mixed phenotype acute leukemia (MPAL) are assigned to 1 of 2 regimens, by physician discretion. Patients with acute myeloid leukemia (AML) are assigned to Regimen B.

REGIMEN A:

COMBINATION CYCLE 1: Patients receive revumenib orally (PO) or via nasogastric (NG), nasojejunal (NJ), nasoduodenal (ND) or gastrostomy tube (G-tube) every 12 hours continuously. Patients also receive "3-drug re-induction" consisting of vincristine intravenously (IV) on days 1, 8, 15, and 22, prednisone or prednisolone PO or via NG, ND, NJ, or G-tube twice daily (BID) on days 1-28, calaspargase pegol IV on day 4, as well as methotrexate (MTX) intrathecally (IT) on days 1 and 8 then optionally weekly, hydrocortisone IT, and cytarabine IT. Patients who have early progressive disease may continue to Combination Cycle 2 early before fully completing cycle 1.

COMBINATION CYCLE 2: Patients receive revumenib PO or via NG, NJ, ND, or G-tube every 12 hours continuously, "FLA" consisting of fludarabine IV and high-dose cytarabine IV on days 1-5, and MTX IT, hydrocortisone IT, and cytarabine IT on day 0 then optionally on days 8, 15, and 22. After completion of Combination Cycle 2, patients who experienced early progressive disease in Combination Cycle 1 continue to Combination Cycle 3. All other patients proceed to Monotherapy.

COMBINATION CYCLE 3: Patients receive revumenib PO or via NG, NJ, ND, or G-tube every 12 hours continuously, "FLA" as in Combination Cycle 2, MTX IT, hydrocortisone IT, and cytarabine IT on day 0.

MONOTHERAPY: Patients receive revumenib PO or via NG, NJ, ND, or G-tube every 12 hours continuously. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive MTX IT, hydrocortisone IT, and cytarabine IT.

REGIMEN B:

COMBINATION CYCLES 1-2: Patients receive revumenib PO or via NG, ND, NJ, or G-tube every 12 hours continuously, "FLA" consisting of fludarabine IV and high-dose cytarabine IV on days 1-5, and MTX IT, hydrocortisone IT, and cytarabine IT on day 0 then optionally on days 8, 15, and 22. Cycles are a minimum of 29 days in duration.

MONOTHERAPY: Patients receive revumenib PO or via NG, ND, NJ, or G-tube every 12 hours continuously. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive MTX IT, hydrocortisone IT, and cytarabine IT.

All patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA), electrocardiogram (ECG), collection of blood, cerebrospinal fluid (CSF) and bone marrow samples, lumbar puncture, and bone marrow aspiration throughout the trial.

Being tested
Biospecimen Collection, Bone Marrow Aspiration, Calaspargase Pegol, Cytarabine, Echocardiography Test
Medical subject headings
Leukemia, Biphenotypic, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma

What participants receive

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

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of blood and CSF samples

  • Bone Marrow AspirationProcedure or surgery

    Undergo bone marrow aspiration

  • Calaspargase PegolDrug

    Also called Asparaginase (Escherichia coli Isoenzyme II), Conjugate with alpha-(((2,5-Dioxo-1-pyrrolidinyl)oxy)carbonyl)-omega-methoxypoly(oxy-1,2-ethanediyl), Asparlas, Calaspargase Pegol-mknl, EZN-2285

    Given IV

  • CytarabineDrug

    Also called .beta.-Cytosine arabinoside, 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone, 1-.beta.-D-Arabinofuranosylcytosine, 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone

    Given IV and IT

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • ElectrocardiogramProcedure or surgery

    Also called ECG, EKG, Electrocardiograms

    Undergo ECG

  • Fludarabine PhosphateDrug

    Also called 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara

    Given IV

  • Hydrocortisone Sodium SuccinateDrug

    Also called (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt, A-Hydrocort, Buccalsone, Corlan

    Given IT

  • Lumbar PunctureProcedure or surgery

    Also called LP, Spinal Tap

    Undergo lumbar puncture

  • MethotrexateDrug

    Also called Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate

    Given IT

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA scan

  • PrednisoloneDrug

    Also called (11beta)-11,17,21-Trihydroxypregna-1,4-diene-3,20-dione, .delta.1-Hydrocortisone, Adnisolone, Aprednislon

    Given PO or via NG, NJ, ND or G-tube

  • PrednisoneDrug

    Also called .delta.1-Cortisone, 1, 2-Dehydrocortisone, Adasone, Cortancyl

    Given PO or via NG, NJ, ND or G-tube

  • RevumenibDrug

    Also called Menin-Mixed Lineage Leukemia Protein-Protein Interaction Inhibitor SNDX-5613, Menin-MLL Inhibitor SNDX-5613, Menin-MLL Interaction Inhibitor SNDX-5613, SNDX 5613

    Given PO or via NG, NJ, ND or G-tube

  • Vincristine SulfateDrug

    Also called Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin

    Given IV

Study groups in NCT05761171
Study groupRoleWhat they receive
Regimen A (revumenib, 3-drug re-induction, FLA)ExperimentalSee Detailed Description.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Drug: Calaspargase Pegol; Drug: Cytarabine; Procedure: Echocardiography Test; Procedure: Electrocardiogram; Drug: Fludarabine Phosphate; Drug: Hydrocortisone Sodium Succinate; Procedure: Lumbar Puncture; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Prednisolone; Drug: Prednisone; Drug: Revumenib; Drug: Vincristine Sulfate
Regimen B (revumenib, FLA)ExperimentalCOMBINATION CYCLES 1-2: Patients receive revumenib PO or via NG, ND, NJ, or G-tube every 12 hours continuously, "FLA" consisting of fludarabine IV and high-dose cytarabine IV on days 1-5, and MTX IT, hydrocortisone IT, and cytarabine IT on day 0 then optionally on days 8, 15, and 22. Cycles are a minimum of 29 days in duration. MONOTHERAPY: Patients receive revumenib PO or via NG, ND, NJ, or G-tube every 12 hours continuously. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients may also receive MTX IT, hydrocortisone IT, and cytarabine IT. All patients also undergo ECHO or MUGA, ECG, collection of blood, CSF and bone marrow samples, lumbar puncture, and bone marrow aspiration throughout the trial.
Receives: Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Drug: Cytarabine; Procedure: Echocardiography Test; Procedure: Electrocardiogram; Drug: Fludarabine Phosphate; Drug: Hydrocortisone Sodium Succinate; Procedure: Lumbar Puncture; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Revumenib

What is being measured

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

  1. Incidence of dose-limiting toxicities (DLTs) for lymphoid directed chemotherapy block (Safety Phase)

    Regimen A Cycle 1 will be used for determination of recommended phase 2 dose (RP2D)-lymphoid (L) directed chemotherapy block. A patient will be considered as being evaluable for DLT if: (1) the patient receives at least 44 doses of the first planned 28 days (56 doses) of revumenib for cycle 1 (for patients with delayed revumenib shipment, will count 28 days from the start of revumenib); or (2) the patient experiences a DLT after the start of revumenib in that cycle.

    Measured: At the end of Cycle 1 of Regimen A (each cycle is a minimum of 29 days)

  2. Incidence of dose-limiting toxicities (DLTs) for myeloid directed chemotherapy block (Safety Phase)

    Regimen B Cycle 1 and Regimen A Cycle 2 will be used for determination of RP2D-myeloid (M) directed chemotherapy block. For each cycle mentioned above, a patient will be considered as being evaluable for DLT if: (1) the patient receives at least 44 doses of the first planned 28 days (56 doses) of revumenib for the cycle (for patients with delayed revumenib shipment, will count 28 days from the start of revumenib); or (2) the patient experiences a DLT after the start of revumenib in that cycle. For determination of RP2D-M, patients in Regimen A who have experienced a DLT in Cycle 1 or who have been evaluated as having Early Progressive Disease in Cycle 1 are excluded.

    Measured: At the end of Cycle 1 of Regimen B and at the end of Cycle 2 of Regimen A (each cycle is a minimum of 29 days)

  3. Minimal residual disease (MRD) negative remission rate in patients with relapsed/refractory (R/R) infant KMT2A-R ALL among patients >= 6 months at enrollment (Expansion Phase)

    A patient with R/R infant KMT2A-R ALL will be included in the primary analysis of MRD negative remission rate if the patient is enrolled at RP2D-L and RP2D-M (in the safety phase or the expansion phase) and receives at least one dose of protocol treatment. This response rate will be estimated using the approach of Jung and Kim. The corresponding 95% confidence interval will be calculated using the approach of Koyama and Chen.

    Measured: Up to 3 cycles of combination therapy (each cycle is a minimum of 29 days)

Secondary outcomes (4)

  1. Proportion of patients achieving desired SNDX-5613 pharmacokinetics (PK)

    Analyses will be conducted for lymphoid and myeloid blocks separately and then combined. Will monitor if there is evidence that the proportion of patients achieving desired PK is considerably lower than 90% using the Pocock stopping boundaries.

    Measured: Up to 2 years from enrollment

  2. Estimation of 18-month event-free survival (EFS) rate in patients with R/R infant KMT2A-R ALL

    Will be estimated using the Kaplan-Meier method. Cumulative incidence rates of each EFS event type (relapse, SMN and death) will be estimated and be presented with cumulative incidence curves.

    Measured: Time from date of enrollment to date of treatment failure, relapse, second or secondary malignancy (SMN), or death due to any cause, whichever occurs first, assessed up to 18 months

  3. Estimation of 18-month overall survival (OS) rate in patients with R/R infant KMT2A-R ALL

    Will be estimated using the Kaplan-Meier method.

    Measured: Time from date of enrollment to death due to any cause, assessed up to 18 months

  4. Characterization of tolerability of revumenib given as monotherapy in patients with R/R infant KMT2A-R ALL

    Grade 3+ adverse events (AEs) will be summarized among patients receiving monotherapy, by cycles, and the proportion of patients having grade 3+ AEs will be estimated.

    Measured: Up to 2 years from enrollment

Timeline

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

  1. First posted9 Mar 2023
  2. Study start8 Jan 2024
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 Dec 2027 (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 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
78 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05761171
Sponsor's protocol ID
AALL2121
Other IDs
NCI-2023-00503, AALL2121, AALL2121, U10CA180886
Status last verified
Apr 2026
First submitted
2 Feb 2023
Last updated
25 Aug 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Biospecimen Collection, Bone Marrow Aspiration and Calaspargase Pegol in people with Recurrent Acute Leukemia of Ambiguous Lineage and Recurrent Acute Lymphoblastic Leukemia, run by Children's Oncology Group at 84 sites in 2 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 44 inclusion and 24 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: under way, not looking for participants, as of the sponsor's last update on 25 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 84 sites in United States, Canada. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of dose-limiting toxicities (DLTs) for lymphoid directed chemotherapy block (Safety Phase) (time frame: At the end of Cycle 1 of Regimen A (each cycle is a minimum of 29 days)). The study lists 3 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 NCT05761171.

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 25 Aug 2026.

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