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

NCT ID: NCT05761171

Last Updated: 2025-12-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 78 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-08
• Study Completion Date: 2027-12-31

Brief 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) 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.

Detailed Description

PRIMARY OBJECTIVES:

I. 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 with R/R infant KMT2A-R ALL treated with revumenib in combination with chemotherapy.

SECONDARY OBJECTIVES:

I. 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 OBJECTIVE:

I. 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-mknl 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.

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-mknl IV over 1-2 hours 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 over 60 minutes and high-dose cytarabine IV over 1-3 hours on days 1-5. 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. Patients may also receive MTX IT, hydrocortisone IT, and cytarabine IT as clinically indicated.

REGIMEN B:

COMBINATION CYCLES 1-2: Patients receive revumenib PO or via NG, ND, NJ, or G-tube every 12 hours continuously, "FLA" IV on days 1-5, MTX IT, hydrocortisone IT, and cytarabine IT on day 0 and optionally on days 8, 15, and 22 of each cycle. Cycles repeat every 28 days for 2 cycles.

MONOTHERAPY: Patients receive revumenib PO or via NG, ND, NJ, or G-tube every 12 hours continuously. Treatment repeats every 28 days for up to 12 cycles on study in the absence of disease progression or unacceptable toxicity. Patients may also receive MTX IT, hydrocortisone IT, and cytarabine IT on days 0, 8, 15 and 22 as clinically indicated.

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

Conditions

Recurrent Acute Leukemia of Ambiguous Lineage; Recurrent Acute Lymphoblastic Leukemia; Recurrent Acute Myeloid Leukemia Due to Lineage Switch From Acute Leukemia of Ambiguous Lineage; Recurrent Acute Myeloid Leukemia Due to Lineage Switch From B Acute Lymphoblastic Leukemia, KMT2A-Rearranged; Recurrent Acute Myeloid Leukemia Due to Lineage Switch From Mixed Phenotype Acute Leukemia; Recurrent Mixed Phenotype Acute Leukemia; Refractory Acute Leukemia of Ambiguous Lineage; Refractory Acute Lymphoblastic Leukemia; Refractory Acute Myeloid Leukemia Due to Lineage Switch From Acute Leukemia of Ambiguous Lineage; Refractory Acute Myeloid Leukemia Due to Lineage Switch From B Acute Lymphoblastic Leukemia, KMT2A-Rearranged; Refractory Acute Myeloid Leukemia Due to Lineage Switch From Mixed Phenotype Acute Leukemia; Refractory Mixed Phenotype Acute Leukemia

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Regimen A (revumenib, 3-drug re-induction, FLA)

See Detailed Description.

Group Type: EXPERIMENTAL

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo collection of blood and CSF samples

Bone Marrow Aspiration

Intervention Type: PROCEDURE

Undergo bone marrow aspiration

Calaspargase Pegol

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IV and IT

Echocardiography Test

Intervention Type: PROCEDURE

Undergo ECHO

Fludarabine Phosphate

Intervention Type: DRUG

Given IV

Hydrocortisone Sodium Succinate

Intervention Type: DRUG

Given IT

Lumbar Puncture

Intervention Type: PROCEDURE

Undergo lumbar puncture

Methotrexate

Intervention Type: DRUG

Given IT

Multigated Acquisition Scan

Intervention Type: PROCEDURE

Undergo MUGA scan

Prednisolone

Intervention Type: DRUG

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

Prednisone

Intervention Type: DRUG

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

Revumenib

Intervention Type: DRUG

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

Vincristine Sulfate

Intervention Type: DRUG

Given IV

Regimen B (revumenib, FLA)

COMBINATION CYCLES 1-2: Patients receive revumenib PO or via NG, ND, NJ, or G-tube every 12 hours continuously, "FLA" IV on days 1-5, MTX IT, hydrocortisone IT, and cytarabine IT on day 0 and optionally on days 8, 15, and 22 of each cycle. Cycles repeat every 28 days for 2 cycles.

MONOTHERAPY: Patients receive revumenib PO or via NG, ND, NJ, or G-tube every 12 hours continuously. Treatment repeats every 28 days for up to 12 cycles on study in the absence of disease progression or unacceptable toxicity. Patients may also receive MTX IT, hydrocortisone IT, and cytarabine IT on days 0, 8, 15 and 22 as clinically indicated.

All patients also undergo ECHO or MUGA, collection of blood and CSF samples, lumbar puncture, and bone marrow aspiration throughout the trial.

Group Type: EXPERIMENTAL

Biospecimen Collection

Intervention Type: PROCEDURE

Undergo collection of blood and CSF samples

Bone Marrow Aspiration

Intervention Type: PROCEDURE

Undergo bone marrow aspiration

Cytarabine

Intervention Type: DRUG

Given IV and IT

Echocardiography Test

Intervention Type: PROCEDURE

Undergo ECHO

Fludarabine Phosphate

Intervention Type: DRUG

Given IV

Hydrocortisone Sodium Succinate

Intervention Type: DRUG

Given IT

Lumbar Puncture

Intervention Type: PROCEDURE

Undergo lumbar puncture

Methotrexate

Intervention Type: DRUG

Given IT

Multigated Acquisition Scan

Intervention Type: PROCEDURE

Undergo MUGA scan

Revumenib

Intervention Type: DRUG

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

Interventions

Biospecimen Collection

Undergo collection of blood and CSF samples

Intervention Type: PROCEDURE

Bone Marrow Aspiration

Undergo bone marrow aspiration

Intervention Type: PROCEDURE

Calaspargase Pegol

Given IV

Intervention Type: DRUG

Cytarabine

Given IV and IT

Intervention Type: DRUG

Echocardiography Test

Undergo ECHO

Intervention Type: PROCEDURE

Fludarabine Phosphate

Given IV

Intervention Type: DRUG

Hydrocortisone Sodium Succinate

Given IT

Intervention Type: DRUG

Lumbar Puncture

Undergo lumbar puncture

Intervention Type: PROCEDURE

Methotrexate

Given IT

Intervention Type: DRUG

Multigated Acquisition Scan

Undergo MUGA scan

Intervention Type: PROCEDURE

Prednisolone

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

Intervention Type: DRUG

Prednisone

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

Intervention Type: DRUG

Revumenib

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

Intervention Type: DRUG

Vincristine Sulfate

Given IV

Intervention Type: DRUG

Other Intervention Names

Biological Sample Collection; Biospecimen Collected; Specimen Collection; 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; SC-PEG E. Coli L-Asparaginase; Succinimidyl Carbonate Monomethoxypolyethylene Glycol E. coli L-Asparaginase; .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; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-Cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453; EC; Echocardiography; 2-F-ara-AMP; 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-; Beneflur; Fludara; SH T 586; (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt; A-Hydrocort; Buccalsone; Corlan; Cortisol Sodium Succinate; Cortop; Efcortelan; Emergent-EZ; Flebocortid; Hidroc Clora; Hycorace; Hydro-Adreson; Hydrocort; Hydrocortisone 21-Sodium Succinate; Hydrocortisone Na Succinate; Kinogen; Nordicort; Nositrol; Sinsurrene; Sodium hydrocortisone succinate; Solu-Cortef; Solu-Glyc; LP; Spinal Tap; Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; Jylamvo; Lantarel; Ledertrexate; Lumexon; Maxtrex; Medsatrexate; Metex; Methoblastin; Methotrexate LPF; Methotrexate Methylaminopterin; Methotrexatum; Metotrexato; Metrotex; Mexate; Mexate-AQ; MTX; Novatrex; Rheumatrex; Texate; Tremetex; Trexeron; Trixilem; WR-19039; Blood Pool Scan; Equilibrium Radionuclide Angiography; Gated Blood Pool Imaging; Gated Heart Pool Scan; MUGA; MUGA Scan; Multi-Gated Acquisition Scan; Radionuclide Ventriculogram Scan; Radionuclide Ventriculography; RNV Scan; RNVG; SYMA Scanning; Synchronized Multigated Acquisition Scanning; (11beta)-11,17,21-Trihydroxypregna-1,4-diene-3,20-dione; .delta.1-Hydrocortisone; Adnisolone; Aprednislon; Capsoid; Cortalone; Cortisolone; Dacortin H; Decaprednil; Decortin H; Delta(1)Hydrocortisone; Delta- Cortef; Delta-Cortef; Delta-Diona; Delta-F; Delta-Phoricol; Delta1-dehydro-hydrocortisone; Deltacortril; Deltahydrocortisone; Deltasolone; Deltidrosol; Dhasolone; Di-Adreson-F; Dontisolon D; Estilsona; Fisopred; Frisolona; Gupisone; Hostacortin H; Hydeltra; Hydeltrasol; Klismacort; Kuhlprednon; Lenisolone; Lepi-Cortinolo; Linola-H N; Linola-H-Fett N; Longiprednil; Metacortandralone; Meti Derm; Meticortelone; Opredsone; Panafcortelone; Precortisyl; Pred-Clysma; Predeltilone; Predni-Coelin; Predni-Helvacort; Prednicortelone; Prednisolonum; Prelone; Prenilone; Sterane; .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltasone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Orasone; Panafcort; Panasol-S; Paracort; Perrigo Prednisone; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisone Intensol; Prednisonum; Prednitone; Promifen; Rayos; Servisone; SK-Prednisone; Menin-Mixed Lineage Leukemia Protein-Protein Interaction Inhibitor SNDX-5613; Menin-MLL Inhibitor SNDX-5613; Menin-MLL Interaction Inhibitor SNDX-5613; SNDX 5613; SNDX-5613; SNDX5613; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Oncovin; Vincasar; Vincosid; Vincrex; Vincristine, sulfate

Eligibility Criteria

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. 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.

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.

• 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: Patients who require concomitant therapy with strong CYP3A4 inhibitors or moderate or strong CYP3A4 inducers, as these are prohibited during the chemotherapy combination cycles. These agents should be discontinued at least 5 half-lives prior to starting protocol therapy. Concomitant use of strong CYP3A4 inhibitor -azole antifungals are 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.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Oncology Group

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kelly E Faulk

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

Children's Hospital of Alabama

Birmingham, Alabama, United States

Arkansas Children's Hospital

Little Rock, Arkansas, United States

Kaiser Permanente Downey Medical Center

Downey, California, United States

Loma Linda University Medical Center

Loma Linda, California, United States

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

UF Health Cancer Institute - Gainesville

Gainesville, Florida, United States

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Nicklaus Children's Hospital

Miami, Florida, United States

AdventHealth Orlando

Orlando, Florida, United States

Arnold Palmer Hospital for Children

Orlando, Florida, United States

Nemours Children's Hospital

Orlando, Florida, United States

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

Tampa, Florida, United States

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, United States

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Children's Hospital of Michigan

Detroit, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, United States

Renown Regional Medical Center

Reno, Nevada, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

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

New Brunswick, New Jersey, United States

Newark Beth Israel Medical Center

Newark, New Jersey, United States

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Albany Medical Center

Albany, New York, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

State University of New York Upstate Medical University

Syracuse, New York, United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Sanford Broadway Medical Center

Fargo, North Dakota, United States

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Dayton Children's Hospital

Dayton, Ohio, United States

Legacy Emanuel Children's Hospital

Portland, Oregon, United States

Oregon Health and Science University

Portland, Oregon, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Prisma Health Richland Hospital

Columbia, South Carolina, United States

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Medical City Dallas Hospital

Dallas, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Children's Hospital of San Antonio

San Antonio, Texas, United States

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Seattle Children's Hospital

Seattle, Washington, United States

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

IWK Health Centre

Halifax, Nova Scotia, Canada

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Children's Hospital

London, Ontario, Canada

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Hospital for Sick Children

Toronto, Ontario, Canada

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, Canada

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

Québec, , Canada

Countries

United States; Canada

Other Identifiers

NCI-2023-00503

Identifier Type: REGISTRY

Identifier Source: secondary_id

AALL2121

Identifier Type: OTHER

Identifier Source: secondary_id

AALL2121

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA180886

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AALL2121

Identifier Type: -

Identifier Source: org_study_id