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

NCT05761171 | Active Not Recruiting Phase 2 FDA Drug

• 3 other identifiers: AALL2121NCI-2023-00503U10CA180886
• Study Type: interventional
• Target: 78
• Locations: 2 countries
• Sites: 84

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.

Conditions

Recurrent Acute Leukemia of Ambiguous Lineage; Recurrent Acute Lymphoblastic Leukemia; 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; Recurrent Acute Myeloid Leukemia Due to Lineage Switch From Acute Leukemia of Ambiguous Lineage

Outcome Measures

Primary Outcomes (3)

• 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.

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

• 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.

  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)

• 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.

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

Secondary Outcomes (4)

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

  Up to 2 years from enrollment

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

  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

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

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

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

  Up to 2 years from enrollment

Other Outcomes (6)

• Changes in KMT2A-R transcriptional program

  Up to 5 years from enrollment

• Changes to menin displacement

  Up to 5 years from enrollment

• MRD negative remission rates in patients with R/R non-infant KMT2A-R ALL

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

Study Arms (2)

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

EXPERIMENTAL

See Detailed Description.

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)

EXPERIMENTAL

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 ECHO or MUGA, ECG, collection of blood, CSF and bone marrow samples, lumbar puncture, and bone marrow aspiration throughout the trial.

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

Interventions

Calaspargase Pegol DRUG

Given IV

Also known as: 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

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

Cytarabine DRUG

Given IV and IT

Also known as: .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

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

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

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

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

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

Hydrocortisone Sodium Succinate DRUG

Given IT

Also known as: (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

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

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

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

Methotrexate DRUG

Given IT

Also known as: 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

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

Multigated Acquisition Scan PROCEDURE

Undergo MUGA scan

Also known as: 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

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

Prednisolone DRUG

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

Also known as: (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

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

Prednisone DRUG

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

Also known as: .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

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

Revumenib DRUG

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

Also known as: 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

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

Vincristine Sulfate DRUG

Given IV

Also known as: Kyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfate

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

Biospecimen Collection PROCEDURE

Undergo collection of blood and CSF samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

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

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

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

Electrocardiogram PROCEDURE

Undergo ECG

Also known as: ECG, EKG, Electrocardiograms

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

Eligibility Criteria

• Age: 1 Month - 6 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Children's Oncology Group: lead

Study Sites (84)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States

Location

Kaiser Permanente Downey Medical Center

Downey, California, 90242, United States

Location

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

Location

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

Location

Kaiser Permanente-Oakland

Oakland, California, 94611, United States

Location

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

Location

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, 33908, United States

Location

UF Health Cancer Institute - Gainesville

Gainesville, Florida, 32610, United States

Location

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

Location

Nicklaus Children's Hospital

Miami, Florida, 33155, United States

Location

AdventHealth Orlando

Orlando, Florida, 32803, United States

Location

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

Location

Nemours Children's Hospital

Orlando, Florida, 32827, United States

Location

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

Tampa, Florida, 33607, United States

Location

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

Location

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

Location

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

Location

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Children's Hospital of Michigan

Detroit, Michigan, 48201, United States

Location

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

Location

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, 68114, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, 89135, United States

Location

Renown Regional Medical Center

Reno, Nevada, 89502, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

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

New Brunswick, New Jersey, 08903, United States

Location

Newark Beth Israel Medical Center

Newark, New Jersey, 07112, United States

Location

University of New Mexico Cancer Center

Albuquerque, New Mexico, 87106, United States

Location

Albany Medical Center

Albany, New York, 12208, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27599, United States

Location

Sanford Broadway Medical Center

Fargo, North Dakota, 58122, United States

Location

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

Location

Legacy Emanuel Children's Hospital

Portland, Oregon, 97227, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, 19134, United States

Location

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

Location

Prisma Health Richland Hospital

Columbia, South Carolina, 29203, United States

Location

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, 29605, United States

Location

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, 57117-5134, United States

Location

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, 37203, United States

Location

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

Location

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

Location

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

Location

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Children's Hospital of San Antonio

San Antonio, Texas, 78207, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

CancerCare Manitoba

Winnipeg, Manitoba, R3E 0V9, Canada

Location

IWK Health Centre

Halifax, Nova Scotia, B3K 6R8, Canada

Location

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, L8N 3Z5, Canada

Location

Children's Hospital

London, Ontario, N6A 5W9, Canada

Location

Children's Hospital of Eastern Ontario

Ottawa, Ontario, K1H 8L1, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Centre Hospitalier Universitaire Sainte-Justine

Montreal, Quebec, H3T 1C5, Canada

Location

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

Québec, G1V 4G2, Canada

Location

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Specimen Handling; calaspargase pegol; Asparaginase; Cytarabine; fludarabine phosphate; Hydrocortisone; hydrocortisone hemisuccinate; Spinal Puncture; Methotrexate; merphos; Prednisolone; Methylprednisolone; Prednisone; deltacortene; prednylidene; revumenib; Vincristine

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Biopsy; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnadienediols; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Kelly E Faulk

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 2, 2023
• First Posted: March 9, 2023
• Study Start: January 8, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 21, 2026

Record last verified: 2026-04

Locations

US (75); CA (9)