Testing the Addition of the Anti-cancer Drug Venetoclax and/or the Anti-cancer Immunotherapy Blinatumomab to the Usual Chemotherapy Treatment for Infants With Newly Diagnosed KMT2A-rearranged or KMT2A-non-rearranged Leukemia

NCT06317662 | Recruiting Phase 2 FDA Drug

• 3 other identifiers: NCI-2024-01994AALL2321U10CA180886
• Study Type: interventional
• Target: 153
• Locations: 2 countries
• Sites: 107

Brief Summary

This phase II trial tests the addition of venetoclax and/or blinatumomab to usual chemotherapy for treating infants with newly diagnosed acute lymphoblastic leukemia (ALL) with a KMT2A gene rearrangement (KMT2A-rearranged \[R\]) or without a KMT2A gene rearrangement (KMT2A-germline \[G\]). Venetoclax is in a class of medications called B-cell lymphoma-2 (Bcl-2) inhibitors. It may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Blinatumomab is a monoclonal antibody that may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs 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. Adding venetoclax and/or blinatumomab to standard chemotherapy may be more effective at treating patients with ALL than standard chemotherapy alone, but it may also cause more side effects. This clinical trial evaluates the safety and effectiveness of adding venetoclax and/or blinatumomab to chemotherapy for the treatment of infants with KMT2A-R or KMT2A-G ALL.

Conditions

B Acute Lymphoblastic Leukemia; Acute Leukemia of Ambiguous Lineage

Outcome Measures

Primary Outcomes (3)

• Incidence of dose-limiting toxicities (DLTs) (safety phase)

  For the safety phase, DLTs of the induction + venetoclax cycle of KMT2A-rearranged (R) patients will be assessed.

  For the duration of the induction + venetoclax cycle

• Incidence of DLTs (expansion phase)

  For the expansion phase, DLTs of Arm B will be assessed and monitored for the cycles that contain venetoclax (induction, consolidation, and MARMA cycles of Arm B).

  During the induction, consolidation, and MARMA cycles of Arm B

• Minimal residual disease (MRD)-negative remission rate

  The end of induction MRD-negative remission rate will be compared between Arm A and Arm B. MRD negativity is defined as achievement of complete remission and MRD \< 0.01% by flow cytometry. The MRD-negative remission rate at the end of induction between Arm A and Arm B will be compared using a one-sided Z test of proportions with Type I error of 0.15.

  At the end of induction

Secondary Outcomes (6)

• MRD-negative remission rate

  At the end of induction

• Event free survival (EFS) rates of infants with KMT2A-R ALL

  From date of randomization to treatment failure, first documented relapse following achievement of remission-1, occurrence of a second or secondary malignant neoplasm, or death, assessed up to 3 years

• 3-year EFS of infants with KMT2A-R ALL

  From date of randomization to treatment failure, first documented relapse following achievement of remission-1, occurrence of a second or secondary malignant neoplasm, or death, assessed up to 3 years

• Proportion of KMT2A-germline (G) patients in Arm C who are able to receive all treatment cycles before maintenance

  Up to interim maintenance 2

• 3-year EFS of infants with KMT2A-G ALL treated on Arm C

  From date of enrollment to treatment failure, first documented relapse following achievement of remission-1, occurrence of a second or secondary malignant neoplasm, or death, assessed up to 3 years

Other Outcomes (8)

• 3-year EFS of infants with KMT2A-R ALL treated on Arm B

  From date of randomization to treatment failure, first documented relapse following achievement of remission-1, occurrence of a second or secondary malignant neoplasm, or death, assessed up to 3 years

• Use of high-throughput sequencing (HTS) for MRD detection in infant ALL compared to centralized flow cytometry

  Up to 3 years

• PK of calaspargase pegol in infants with ALL

  At completion of the trial, up to 3 years

Study Arms (8)

Arm A

EXPERIMENTAL

See Detailed Description for Arm A.

Drug: Asparaginase Erwinia chrysanthemi; Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Procedure: Echocardiography Test; Procedure: FDG-Positron Emission Tomography; Drug: Leucovorin; Drug: Levoleucovorin; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Drug: Vincristine

Arm B, Cohort 1

EXPERIMENTAL

See Detailed Description for Arm B, Cohort 1.

Drug: Asparaginase Erwinia chrysanthemi; Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Procedure: Echocardiography Test; Procedure: FDG-Positron Emission Tomography; Drug: Leucovorin; Drug: Levoleucovorin; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Drug: Venetoclax; Drug: Vincristine

Arm B, Cohort 2

EXPERIMENTAL

See Detailed Description for Arm B, Cohort 2.

Drug: Asparaginase Erwinia chrysanthemi; Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Procedure: Echocardiography Test; Procedure: FDG-Positron Emission Tomography; Drug: Leucovorin; Drug: Levoleucovorin; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Drug: Venetoclax; Drug: Vincristine

Arm B, Cohort 3

EXPERIMENTAL

See Detailed Description for Arm B, Cohort 3.

Drug: Asparaginase Erwinia chrysanthemi; Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Procedure: Echocardiography Test; Procedure: FDG-Positron Emission Tomography; Drug: Leucovorin; Drug: Levoleucovorin; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Drug: Venetoclax; Drug: Vincristine

Arm B, Cohort 4

EXPERIMENTAL

See Detailed Description for Arm B, Cohort 4.

Drug: Asparaginase Erwinia chrysanthemi; Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Procedure: Echocardiography Test; Procedure: FDG-Positron Emission Tomography; Drug: Leucovorin; Drug: Levoleucovorin; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Drug: Venetoclax; Drug: Vincristine

Arm C

EXPERIMENTAL

See Detailed Description for Arm C.

Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography Test; Procedure: FDG-Positron Emission Tomography; Drug: Leucovorin; Drug: Levoleucovorin; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine; Drug: Methotrexate; Drug: Methylprednisolone; Procedure: Multigated Acquisition Scan; Drug: Prednisolone; Drug: Prednisone; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Drug: Vincristine

Safety Phase Cohort

EXPERIMENTAL

See Detailed Description for Safety Phase Cohort.

Drug: Asparaginase Erwinia chrysanthemi; Procedure: Biospecimen Collection; Biological: Blinatumomab; Procedure: Bone Marrow Aspiration; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Procedure: Echocardiography Test; Procedure: FDG-Positron Emission Tomography; Drug: Leucovorin; Drug: Levoleucovorin; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Drug: Venetoclax; Drug: Vincristine

Steroid Prephase(prednisone, prednisolone, methylprednisolone)

EXPERIMENTAL

All patients receive prednisone or prednisolone PO or NG TID or methylprednisolone IV TID for 7 days prior to the start of induction therapy (on days 1-7).

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Computed Tomography; Procedure: Echocardiography Test; Procedure: FDG-Positron Emission Tomography; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Methylprednisolone; Procedure: Multigated Acquisition Scan; Drug: Prednisolone; Drug: Prednisone

Interventions

Asparaginase Erwinia chrysanthemi DRUG

Given recombinant crisantaspase IM or crisantaspase IM or IV

Also known as: Asparaginase Erwinia chrysanthemi (Recombinant)-rywn, Asparaginase Erwinia chrysanthemi, Recombinant-rywn, Asparaginase Erwinia chrysanthemi-rywn, Crisantaspase, Crisantaspase Biobetter JZP-458, Crisantaspasum, Enrylaze, Erwinase, Erwinaze, JZP 458, JZP-458, JZP458, PF743, RC-P JZP-458, Recombinant Asparaginase erwinia chrysanthemi JZP-458, Recombinant Crisantaspase JZP-458, Recombinant Erwinia asparaginase JZP-458, Rylaze

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Safety Phase Cohort

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

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

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort; Steroid Prephase(prednisone, prednisolone, methylprednisolone)

Blinatumomab BIOLOGICAL

Given IV

Also known as: AMG 103, AMG-103, AMG103, Anti-CD19 x Anti-CD3 Bispecific Monoclonal Antibody, Anti-CD19/Anti-CD3 Recombinant Bispecific Monoclonal Antibody MT103, Blincyto, MEDI 538, MEDI-538, MEDI538, MT 103, MT-103, MT103

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort; Steroid Prephase(prednisone, prednisolone, methylprednisolone)

Cyclophosphamide DRUG

Given IV

Also known as: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Asta B 518, B 518, B-518, B518, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamide Monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR 138719, WR- 138719, WR-138719, WR138719

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort

Levoleucovorin DRUG

Given IV

Also known as: CL-307,782, Elvorine, Isovorin, Levofolene, Levorin, Isovorin, L-Leucovorin, Levofolinate, Levofolinic acid

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort; Steroid Prephase(prednisone, prednisolone, methylprednisolone)

Methotrexate DRUG

Given IT or IV or PO or NG

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

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort

Prednisolone DRUG

Given PO or NG

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

Arm C; Steroid Prephase(prednisone, prednisolone, methylprednisolone)

Prednisone DRUG

Given PO or NG

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

Arm C; Steroid Prephase(prednisone, prednisolone, methylprednisolone)

Therapeutic Hydrocortisone DRUG

Given IT

Also known as: Aeroseb-HC, Barseb HC, Barseb-HC, Cetacort, Cort-Dome, Cortef, Cortenema, Cortifan, Cortisol, Cortispray, Cortril, Dermacort, Domolene, Eldecort, Hautosone, Heb-Cort, Hydrocortisone, Hydrocortone, Hytone, Komed-HC, Nutracort, Proctocort, Rectoid

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort

Thioguanine DRUG

Given PO or NG

Also known as: 2-Amino 6MP, 2-Amino-1,7-dihydro-6H-purine-6-thione, 2-Amino-6-mercaptopurine, 2-Amino-6-purinethiol, 2-Aminopurin-6-thiol, 2-Aminopurine-6(1H)-thione, 2-Aminopurine-6-thiol, 2-Aminopurine-6-thiol Hemihydrate, 2-Mercapto-6-aminopurine, 6-Amino-2-mercaptopurine, 6-Mercapto-2-aminopurine, 6-Mercaptoguanine, 6-TG, 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI), BW 5071, Lanvis, Tabloid, Thioguanine Hemihydrate, Thioguanine Hydrate, Tioguanin, Tioguanine, Wellcome U3B, WR-1141, X 27

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort

Venetoclax DRUG

Given PO or NG

Also known as: ABT 199, ABT-0199, ABT-199, ABT199, GDC 0199, GDC-0199, GDC0199, RG7601, Venclexta, Venclyxto

Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Safety Phase Cohort

Vincristine DRUG

Given IV

Also known as: LCR, Leurocristine, VCR, Vincrystine

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort

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

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort; Steroid Prephase(prednisone, prednisolone, methylprednisolone)

Cytarabine DRUG

Given IT or IV

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

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort

Daunorubicin DRUG

Given IV

Also known as: Daunomycin, Daunorrubicina, DNR, Leukaemomycin C, Rubidomycin, Rubomycin C

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort

Dexamethasone DRUG

Given PO or NG or IV

Also known as: Aacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycadron, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, Decadron DP, Decalix, Decameth, Decasone R.p., Dectancyl, Dekacort, Deltafluorene, Deronil, Desamethasone, Desameton, Dexa-Mamallet, Dexa-Rhinosan, Dexa-Scheroson, Dexa-sine, Dexacortal, Dexacortin, Dexafarma, Dexafluorene, Dexalocal, Dexamecortin, Dexameth, Dexamethasone Intensol, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Dxevo, Fluorodelta, Fortecortin, Gammacorten, Hemady, Hexadecadrol, Hexadrol, LenaDex, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort

Doxorubicin DRUG

Given IV

Also known as: Adriablastin, Hydroxydaunomycin, Hydroxyl Daunorubicin, Hydroxyldaunorubicin

Arm C

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort; Steroid Prephase(prednisone, prednisolone, methylprednisolone)

FDG-Positron Emission Tomography PROCEDURE

Undergo FDG-PET

Also known as: FDG, FDG-PET, FDG-PET Imaging

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort; Steroid Prephase(prednisone, prednisolone, methylprednisolone)

Leucovorin DRUG

Given PO or NG or IV

Also known as: Folinic acid

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort

Mercaptopurine DRUG

Given PO or NG

Also known as: 3H-Purine-6-thiol, 6 MP, 6 Thiohypoxanthine, 6 Thiopurine, 6-Mercaptopurine, 6-Mercaptopurine Monohydrate, 6-MP, 6-Purinethiol, 6-Thiopurine, 6-Thioxopurine, 6H-Purine-6-thione, 1,7-dihydro- (9CI), 7-Mercapto-1,3,4,6-tetrazaindene, Alti-Mercaptopurine, Azathiopurine, Bw 57-323H, Flocofil, Ismipur, Leukerin, Leupurin, Mercaleukim, Mercaleukin, Mercaptina, Mercaptopurinum, Mercapurin, Mern, NCI-C04886, Puri-Nethol, Purimethol, Purine, 6-mercapto-, Purine-6-thiol (8CI), Purine-6-thiol, monohydrate, Purinethiol, Purinethol, U-4748, WR-2785

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

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

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort; Steroid Prephase(prednisone, prednisolone, methylprednisolone)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Arm A; Arm B, Cohort 1; Arm B, Cohort 2; Arm B, Cohort 3; Arm B, Cohort 4; Arm C; Safety Phase Cohort; Steroid Prephase(prednisone, prednisolone, methylprednisolone)

Methylprednisolone DRUG

Given IV

Also known as: Adlone, Caberdelta M, DepMedalone, Depo Moderin, Depo-Nisolone, Duralone, Emmetipi, Esametone, Firmacort, Medlone 21, Medrate, Medrol, Medrol Veriderm, Medrone, Mega-Star, Meprolone, Methylprednisolonum, Metilbetasone Solubile, Metrocort, Metypresol, Metysolon, Predni-M-Tablinen, Prednilen, Radilem, Sieropresol, Solpredone, Summicort, Urbason, Veriderm Medrol, Wyacort

Arm C; Steroid Prephase(prednisone, prednisolone, methylprednisolone)

Eligibility Criteria

• Age: Up to 365 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• All patients must be enrolled on APEC14B1 and consented to eligibility screening (part A) prior to treatment and enrollment on AALL2321
• Infants (aged 365 days or less) on the date of diagnosis are eligible; infants must be \> 36 weeks gestational age at the time of enrollment
• Patients must have newly diagnosed B-acute lymphoblastic leukemia (B-ALL, 2017 World Health Organization \[WHO\] classification), also termed B-precursor ALL, or acute leukemia of ambiguous lineage (ALAL), which includes mixed phenotype acute leukemia. For patients with ALAL, the immunophenotype of the leukemia must comprise at least 50% B lineage
• Diagnostic immunophenotype: Leukemia cells must express CD19

You may not qualify if:

• Patients with Down Syndrome
• Patients with secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy
• Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of infant ALL or for any cancer diagnosis prior to the initiation of protocol therapy, with the exception of:
• Steroid pretreatment:
• PredniSONE, prednisoLONE, or methylPREDNISolone for ≤ 72 hours (3 days) in the 7 days prior to enrollment. The dose of predniSONE, prednisoLONE or methylPREDNISolone does not affect eligibility
• Inhaled and topical steroids are not considered pretreatment
• Note: Pretreatment with dexamethasone in the 28 days prior to initiation of protocol therapy is not allowed with the exception of a single dose of dexamethasone used during or within 6 hours prior to or after sedation to prevent or treat airway edema. However, prior exposure to ANY steroids that occurred \> 28 days before enrollment does not affect eligibility
• Intrathecal cytarabine or methotrexate:
• An intrathecal dose of cytarabine or methotrexate in the 7 days prior to enrollment does not affect eligibility
• Note: The preference is to defer the diagnostic lumbar puncture with intrathecal chemotherapy to day 1 of induction to allow for cytoreduction of circulating blasts and decrease the potential for central nervous system (CNS) contamination due to a traumatic tap. If done prior to day 1 of induction, these results will be used to determine CNS status
• Hydroxyurea:
• Pretreatment with ≤ 72 hours (3 days) of hydroxyurea in the 7 days prior to enrollment does not affect eligibility
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (107)

Children's Hospital of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Providence Alaska Medical Center

Anchorage, Alaska, 99508, United States

RECRUITING

Banner Children's at Desert

Mesa, Arizona, 85202, United States

RECRUITING

Arkansas Children's Hospital

Little Rock, Arkansas, 72202-3591, United States

RECRUITING

Loma Linda University Medical Center

Loma Linda, California, 92354, United States

RECRUITING

Miller Children's and Women's Hospital Long Beach

Long Beach, California, 90806, United States

RECRUITING

UCSF Benioff Children's Hospital Oakland

Oakland, California, 94609, United States

RECRUITING

Kaiser Permanente-Oakland

Oakland, California, 94611, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

UCSF Medical Center-Mission Bay

San Francisco, California, 94158, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Connecticut Children's Medical Center

Hartford, Connecticut, 06106, United States

RECRUITING

Yale University

New Haven, Connecticut, 06520, United States

RECRUITING

Alfred I duPont Hospital for Children

Wilmington, Delaware, 19803, United States

RECRUITING

Children's National Medical Center

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

RECRUITING

UF Health Cancer Institute - Gainesville

Gainesville, Florida, 32610, United States

RECRUITING

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, 33021, United States

RECRUITING

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, 32207, United States

RECRUITING

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

RECRUITING

AdventHealth Orlando

Orlando, Florida, 32803, United States

RECRUITING

Arnold Palmer Hospital for Children

Orlando, Florida, 32806, United States

RECRUITING

Nemours Children's Hospital

Orlando, Florida, 32827, United States

RECRUITING

Nemours Children's Clinic - Pensacola

Pensacola, Florida, 32504, United States

RECRUITING

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, 33701, United States

RECRUITING

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

Tampa, Florida, 33607, United States

RECRUITING

Saint Mary's Medical Center

West Palm Beach, Florida, 33407, United States

RECRUITING

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, 30329, United States

RECRUITING

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, 96826, United States

RECRUITING

Saint Luke's Cancer Institute - Boise

Boise, Idaho, 83712, United States

RECRUITING

Lurie Children's Hospital-Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, 60453, United States

RECRUITING

Advocate Children's Hospital-Park Ridge

Park Ridge, Illinois, 60068, United States

RECRUITING

Southern Illinois University School of Medicine

Springfield, Illinois, 62702, United States

RECRUITING

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

RECRUITING

Norton Children's Hospital

Louisville, Kentucky, 40202, United States

RECRUITING

Children's Hospital New Orleans

New Orleans, Louisiana, 70118, United States

RECRUITING

Ochsner Medical Center Jefferson

New Orleans, Louisiana, 70121, United States

RECRUITING

Maine Children's Cancer Program

Scarborough, Maine, 04074, United States

RECRUITING

Sinai Hospital of Baltimore

Baltimore, Maryland, 21215, United States

RECRUITING

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

UMass Memorial Medical Center - University Campus

Worcester, Massachusetts, 01655, United States

RECRUITING

C S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

RECRUITING

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, 49503, United States

RECRUITING

Bronson Methodist Hospital

Kalamazoo, Michigan, 49007, United States

RECRUITING

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

RECRUITING

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, 64108, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Mercy Hospital Saint Louis

St Louis, Missouri, 63141, United States

RECRUITING

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, 68114, United States

RECRUITING

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, 03756, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

Morristown Medical Center

Morristown, New Jersey, 07960, United States

RECRUITING

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

New Brunswick, New Jersey, 08903, United States

RECRUITING

Saint Joseph's Regional Medical Center

Paterson, New Jersey, 07503, United States

RECRUITING

Albany Medical Center

Albany, New York, 12208, United States

RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

RECRUITING

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, 11040, United States

RECRUITING

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, 10016, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

NYP/Weill Cornell Medical Center

New York, New York, 10065, United States

RECRUITING

University of Rochester

Rochester, New York, 14642, United States

RECRUITING

State University of New York Upstate Medical University

Syracuse, New York, 13210, United States

RECRUITING

Montefiore Medical Center - Moses Campus

The Bronx, New York, 10467, United States

RECRUITING

New York Medical College

Valhalla, New York, 10595, United States

RECRUITING

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, 27710, United States

RECRUITING

East Carolina University

Greenville, North Carolina, 27834, United States

RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Children's Hospital Medical Center of Akron

Akron, Ohio, 44308, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

RECRUITING

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, 44106, United States

RECRUITING

Dayton Children's Hospital

Dayton, Ohio, 45404, United States

RECRUITING

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Toledo, Ohio, 43606, United States

RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Lehigh Valley Hospital-Cedar Crest

Allentown, Pennsylvania, 18103, United States

RECRUITING

Geisinger Medical Center

Danville, Pennsylvania, 17822, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15224, United States

RECRUITING

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

Prisma Health Richland Hospital

Columbia, South Carolina, 29203, United States

RECRUITING

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, 29605, United States

RECRUITING

Sanford USD Medical Center - Sioux Falls

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

RECRUITING

East Tennessee Childrens Hospital

Knoxville, Tennessee, 37916, United States

RECRUITING

Saint Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, 37203, United States

RECRUITING

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, 37232, United States

RECRUITING

Dell Children's Medical Center of Central Texas

Austin, Texas, 78723, United States

RECRUITING

Driscoll Children's Hospital

Corpus Christi, Texas, 78411, United States

RECRUITING

Medical City Dallas Hospital

Dallas, Texas, 75230, United States

RECRUITING

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, 75390, United States

RECRUITING

El Paso Children's Hospital

El Paso, Texas, 79905, United States

RECRUITING

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

RECRUITING

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Children's Hospital of San Antonio

San Antonio, Texas, 78207, United States

RECRUITING

Methodist Children's Hospital of South Texas

San Antonio, Texas, 78229, United States

RECRUITING

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

RECRUITING

Children's Hospital of The King's Daughters

Norfolk, Virginia, 23507, United States

RECRUITING

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

RECRUITING

Carilion Children's

Roanoke, Virginia, 24014, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, 99204, United States

RECRUITING

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, 54301, United States

RECRUITING

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

University Pediatric Hospital

San Juan, 00926, Puerto Rico

RECRUITING

MeSH Terms

Conditions

Leukemia, Biphenotypic, Acute; Burkitt Lymphoma

Interventions

asparaginase erwinia chrysanthemi recombinant; Asparaginase; Specimen Handling; blinatumomab; N,N-dicyclohexyl-isoborneol-10-sulfonamide; calaspargase pegol; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Doxorubicin; Leucovorin; Levoleucovorin; Spinal Puncture; Magnetic Resonance Spectroscopy; Mercaptopurine; azathiopurine; Methotrexate; merphos; Methylprednisolone; exifone; Medrol Veriderm; Prednisolone; Prednisone; deltacortene; prednylidene; Hydrocortisone; Thioguanine; venetoclax; 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; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Intervention Hierarchy (Ancestors)

Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Biopsy; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Surgical Procedures, Operative; Spectrum Analysis; Chemistry Techniques, Analytical; Sulfhydryl Compounds; Purines; Aminopterin; Pregnadienediols; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Erin H Breese

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: March 16, 2024
• First Posted: March 19, 2024
• Study Start: June 5, 2025
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: April 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

US (106); PR (1)