Testing the Addition of Daratumumab to Chemotherapy for Treating Patients With Newly-Diagnosed T-Cell Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LL)

NCT07072585 | Not Yet Recruiting Phase 2 FDA Drug

• 3 other identifiers: AALL2331NCI-2025-02230U10CA180886
• Study Type: interventional
• Target: 1,708
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II/III trial tests the addition of daratumumab to chemotherapy for treating patients with newly-diagnosed T-ALL and T-LL. Daratumumab is in a class of medications called monoclonal antibodies. It binds to a protein called CD38, which is found on some types of immune cells and cancer cells. Daratumumab may block CD38 and help the immune system kill cancer cells. 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. Giving chemotherapy with daratumumab may kill more cancer cells.

Conditions

Stage II T Lymphoblastic Leukemia/Lymphoma; Stage III T Lymphoblastic Leukemia/Lymphoma; Stage IV T Lymphoblastic Leukemia/Lymphoma; T Acute Lymphoblastic Leukemia; T Lymphoblastic Lymphoma

Outcome Measures

Primary Outcomes (2)

• Event-free survival (EFS) in patients with newly diagnosed T-cell lymphoblastic leukemia (T-ALL)

  Will compare EFS in patients with newly diagnosed T-ALL who are randomized to either receive a modified augmented Berlin-Frankfurt-Munich (aBFM) chemotherapy backbone or a modified aBFM backbone with the addition of daratumumab. Patients without an EFS event will be censored at the date of last follow-up. The survival time analyses assume a Weibull distribution with a shape parameter of 0.45 (based on historical controls). A phase 2/3 design will be used.

  From date of randomization (randomization conducted at the end of induction [EOI]) to date of first event (consolidation failure, interim maintenance failure, relapse, secondary malignant neoplasm [SMN], death from any cause), assessed up to 4 years

• EFS in patients with newly diagnosed T-cell lymphoblastic lymphoma (T-LL)

  Will compare EFS in patients with newly diagnosed T-LL who are randomized to a modified aBFM chemotherapy backbone with bortezomib or to a modified aBFM backbone with bortezomib and the addition of daratumumab. Patients without an EFS event will be censored at the date of last follow-up. The survival time analyses assume a Weibull distribution with a shape parameter of 0.45 (based on historical controls).

  From date of randomization (randomization conducted at the EOI) to date of first event (consolidation failure, relapse, progressive disease, SMN, death from any cause), assessed up to 4 years

Secondary Outcomes (4)

• Health-related quality of life (HRQoL)

  Baseline (at time of randomization) to day 64 of consolidation

• Incidence of therapy-related toxicity and tolerability

  Assessed up to 3 cycles post randomization (each cycle is approximately 2-3 months)

• Overall survival (OS) in patients with newly diagnosed T-ALL

  From date of randomization (randomization conducted at the EOI) to date of death (death due to any cause), assessed up to 4 years

• Overall survival (OS) in patients with newly diagnosed T-LL

  From date of randomization (randomization conducted at the EOI) to date of death (death due to any cause), assessed up to 4 years

Other Outcomes (11)

• EFS from end of induction patients with newly diagnosed T-LL

  Assessed up to 4 years

• OS from end of Induction in patients with newly diagnosed T-LL

  Assessed up to 4 years

• Immunophenotype in T-ALL patients

  Assessed at baseline, end of Induction (Induction is 29 days), and relapse (up to 10 years)

Study Arms (4)

Group I, Arm A (T-ALL, no daratumumab)

ACTIVE COMPARATOR

See Detailed Description

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine Oral Suspension; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Nelarabine; Drug: Pegaspargase; Drug: Prednisolone; Drug: Prednisone; Other: Questionnaire Administration; Radiation: Radiation Therapy; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Procedure: Ultrasound Imaging; Drug: Vincristine Sulfate

Group I, Arm B (T-ALL, daratumumab)

EXPERIMENTAL

See Detailed Description

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Drug: Cyclophosphamide; Drug: Cytarabine; Biological: Daratumumab; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine Oral Suspension; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Nelarabine; Drug: Pegaspargase; Drug: Prednisolone; Drug: Prednisone; Other: Questionnaire Administration; Radiation: Radiation Therapy; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Procedure: Ultrasound Imaging; Drug: Vincristine Sulfate

Group II, Arm C (T-LL, no daratumumab)

ACTIVE COMPARATOR

See Detailed Description

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Bone Scan; Drug: Bortezomib; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine Oral Suspension; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Prednisolone; Drug: Prednisone; Other: Questionnaire Administration; Radiation: Radiation Therapy; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Procedure: Ultrasound Imaging; Drug: Vincristine Sulfate

Group II, Arm D (T-LL, daratumumab)

EXPERIMENTAL

See Detailed Description

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Procedure: Bone Scan; Drug: Bortezomib; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Biological: Daratumumab; Drug: Daunorubicin Hydrochloride; Drug: Dexamethasone; Drug: Doxorubicin Hydrochloride; Procedure: Echocardiography Test; Procedure: Lumbar Puncture; Procedure: Magnetic Resonance Imaging; Drug: Mercaptopurine Oral Suspension; Drug: Methotrexate; Drug: Methylprednisolone; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Prednisolone; Drug: Prednisone; Other: Questionnaire Administration; Radiation: Radiation Therapy; Drug: Therapeutic Hydrocortisone; Drug: Thioguanine; Procedure: Ultrasound Imaging; Drug: Vincristine Sulfate

Interventions

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

Also known as: Biopsy of Bone Marrow, Biopsy, Bone Marrow

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Bone Scan PROCEDURE

Undergo bone scan

Also known as: Bone Scintigraphy

Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Bortezomib DRUG

Given IV or SC

Also known as: [(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, LDP-341, LDP341, MLN 341, MLN-341, MLN341, PS 341, PS-341, PS341, Velcade

Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

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

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

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

Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

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

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Cytarabine DRUG

Given IT or IV or SC

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

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Daratumumab BIOLOGICAL

Given IV

Also known as: Daratumumab Biosimilar HLX15, Daratumumab-fihj, Darzalex, HLX15, HuMax-CD38, JNJ 54767414, JNJ-54767414, JNJ54767414

Group I, Arm B (T-ALL, daratumumab); Group II, Arm D (T-LL, daratumumab)

Daunorubicin Hydrochloride DRUG

Given IV

Also known as: Cerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin, Daunoblastina, Daunoblastine, Daunomycin Hydrochloride, Daunomycin, hydrochloride, Daunorubicin.HCl, Daunorubicini Hydrochloridum, FI-6339, Ondena, RP-13057, Rubidomycin Hydrochloride, Rubilem

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Dexamethasone DRUG

Given PO 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

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Doxorubicin Hydrochloride DRUG

Given IV

Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, FI106, hydroxydaunorubicin, Rubex

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Lumbar Puncture PROCEDURE

Under lumbar puncture

Also known as: LP, Spinal Tap

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

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

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Mercaptopurine Oral Suspension DRUG

Given PO

Also known as: 6-MP Oral Suspension, Purixan, Xaluprine

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Methotrexate DRUG

Given IT or IV or PO

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

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

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

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Nelarabine DRUG

Given IV

Also known as: 2-Amino-6-methoxypurine arabinoside, 506U78, Arranon, Compound 506U78, GW506U78

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab)

Pegaspargase DRUG

Given IV or IM

Also known as: L-Asparaginase with Polyethylene Glycol, Oncaspar, Oncaspar-IV, PEG-Asparaginase, PEG-L-Asparaginase, PEG-L-Asparaginase (Enzon - Kyowa Hakko), PEGLA, Polyethylene Glycol L-Asparaginase, Polyethylene Glycol-L-Asparaginase

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Positron Emission Tomography PROCEDURE

Undergo PET or PET-CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Prednisolone DRUG

Given PO or IV

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

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Prednisone DRUG

Given PO or IV

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

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Questionnaire Administration OTHER

Ancillary studies

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Radiation Therapy RADIATION

Undergo radiation therapy

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

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

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Thioguanine DRUG

Given PO

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

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Ultrasound Imaging PROCEDURE

Undergo ultrasound

Also known as: 2-Dimensional Grayscale Ultrasound Imaging, 2-Dimensional Ultrasound Imaging, 2D-US, Ultrasonography, Ultrasound, Ultrasound Test, Ultrasound, Medical, US

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Vincristine Sulfate DRUG

Given IV

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

Group I, Arm A (T-ALL, no daratumumab); Group I, Arm B (T-ALL, daratumumab); Group II, Arm C (T-LL, no daratumumab); Group II, Arm D (T-LL, daratumumab)

Eligibility Criteria

• Age: 365 Days - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• All patients must be enrolled on APEC14B1 and consented to eligibility screening (part A) prior to treatment and enrolled on AALL2331.
• Patients must be \> 365 days and \< 21 years of age at the time of diagnosis.
• \* Newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or T-lineage lymphoblastic lymphoma (T-LL) stages II-IV.
• Note: A diagnosis of T-ALL is established when leukemic blasts lack myeloperoxidase or evidence of B-lineage derivation (CD19/CD22/CD20), and express either surface or cytoplasmic CD3 or two or more of the antigens CD8, CD7, CD5, CD4, CD2 or CD1a, and are present either in peripheral blood or \> 25% in the bone marrow. If surface CD3 is expressed on all leukemic cells, additional markers of immaturity, including TdT, CD34 or CD99 will be assessed for expression. Cases with uncertain expression will receive additional review within the appropriate Children's Oncology Group (COG) reference laboratory.
• For T-LL patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to T-ALL. For tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of T-LL defined by the submitting institution will be accepted.

You may not qualify if:

• Diagnosis of Down syndrome (trisomy 21).
• Patients with known Charcot-Marie-Tooth disease.
• \* Patients must not have received any cytotoxic chemotherapy for either the current diagnosis of T-ALL, T-LL or for any cancer diagnosis prior to the initiation of protocol therapy on AALL2331 with the exception of:
• Steroid pretreatment: Prednisone or methylprednisolone for ≤ 120 hours (5 days) in the 7 days prior to initiating induction chemotherapy or for ≤ 336 hours (14 days) in the 28 days prior to initiation of protocol therapy does not affect eligibility.
• Intrathecal cytarabine; or
• Pretreatment with hydroxyurea; or
• cGy of chest irradiation, if medically necessary.
• Pre-treatment 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 sedation to prevent or treat airway edema. Patients who receive a single dose of dexamethasone to prevent or treat airway edema in the 28 days preceding diagnosis are eligible for this study.
• \* Female patients who are pregnant since fetal toxicities and teratogenic effects have been noted for several of the study drugs. A pregnancy test is required for female patients of childbearing potential.
• Lactating females who plan to breastfeed their infants.
• Sexually active patients of reproductive potential who have not agreed to use an effective contraceptive method for the duration of their study participation.
• Known severe persistent asthma anytime in the previous two years or uncontrolled asthma of any classification.
• Peripheral neurotoxicity: Pre-existing ≥ grade 2 sensory or motor peripheral neurotoxicity.
• Seizure disorder: Patients must not have an uncontrolled seizure disorder. Patients with a seizure history or a controlled seizure disorder are eligible. A controlled seizure disorder is defined as having stable or decreasing symptoms over the past 3 months without anti-epileptic medications or is on a stable or decreasing dose of anti-epileptic medication.
• \* Patients who are previously known to be seropositive for HIV except for HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months of enrollment on this trial.

Sponsors & Collaborators

• Children's Oncology Group: lead

MeSH Terms

Conditions

Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Biopsy; Specimen Handling; Bortezomib; calaspargase pegol; Asparaginase; Cyclophosphamide; Cytarabine; daratumumab; Daunorubicin; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Doxorubicin; Spinal Puncture; Magnetic Resonance Spectroscopy; Mercaptopurine; Methotrexate; merphos; Methylprednisolone; exifone; Medrol Veriderm; nelarabine; pegaspargase; Prednisolone; Prednisone; deltacortene; prednylidene; Radiotherapy; Radiation; Hydrocortisone; Thioguanine; High-Energy Shock Waves; Vincristine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Organic Chemicals; Pyrazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; 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; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Spectrum Analysis; Chemistry Techniques, Analytical; Sulfhydryl Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines; Pregnadienediols; Physical Phenomena; Pregnenediones; Pregnenes; 11-Hydroxycorticosteroids; Hydroxycorticosteroids; Adrenal Cortex Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; 17-Hydroxycorticosteroids; Ultrasonic Waves; Sound; Radiation, Nonionizing; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines

Study Officials

• Keith J August

  Children's Oncology Group

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 7, 2025
• First Posted: July 18, 2025
• Study Start (Estimated): June 28, 2026
• Primary Completion (Estimated): September 1, 2035
• Study Completion (Estimated): September 1, 2035
• Last Updated: December 31, 2025

Record last verified: 2025-12