Adding Targeted Drugs to Usual Chemotherapy for Adults With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia (T-ALL) and T-Cell Lymphoblastic Lymphoma (T-LBL)

NCT06210750 | Withdrawn Phase 2 FDA Drug

• 3 other identifiers: NCI-2023-09521S2306U10CA180888
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

This phase II trial tests the safety and effectiveness of giving chemotherapy with or without venetoclax and/or navitoclax for the treatment of patients with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or T-cell lymphoblastic lymphoma (T-LBL). 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. Venetoclax and navitoclax are in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. They may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Giving chemotherapy with or without venetoclax and/or navitoclax may be effective treatments for patients with newly diagnosed T-ALL or T-LBL.

Conditions

T Acute Lymphoblastic Leukemia; T Lymphoblastic Lymphoma

Outcome Measures

Primary Outcomes (4)

• Incidence of adverse events (Cohorts 1, 2 and 3)

  National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events will be used to determine severity of toxicity.

  Up to 10 years

• Undetectable minimal residual disease (MRD) (Cohort 1)

  There will be three primary analyses, each comparing an experimental arm with the shared control arm using Fisher's exact test with a one-sided alpha of 10%. All eligible randomized participants will be used in the efficacy comparison.

  At day 29 following induction

• Percent of participants with detectable disease in the bone marrow (Cohort 2)

  Binomial estimates will be reported along with exact 95% confidence intervals.

  At diagnosis and at days 29 and 57

• Undetectable MRD (Cohorts 1 and 3)

  Binomial estimates will be reported along with exact 95% confidence intervals.

  At days 29 and 78

Secondary Outcomes (8)

• Rate of complete remission (CR)

  End of consolidation therapy

• Rate of complete remission with incomplete count recovery (CRi) with and without MRD

  End of consolidation therapy

• Event free survival

  From the date of initial registration on study until the first of the following events: death from any cause, relapse from MRD-negative remission, or completion of protocol therapy without documentation of MRD-negative remission, up to 10 years

• Relapse free survival

  From the date the participant first achieves CR or CRi until relapse from CR/CRi or death from any cause, up to 10 years

• Overall survival

  From the day of registration to death from any cause, up to 10 years

Other Outcomes (3)

• Rates of MRD

  At day 29 (all cohorts), day 78 (cohorts 1 and 3), and day 57 (cohort 2)

• Percentage of participants with ETP and non-ETP immunophenotype

  Diagnosis

• Association of CR/CRi, event-free survival, relapse-free survival, and overall survival with early thymic precursor (ETP) and non-ETP immunophenotype

  Up to 10 years

Study Arms (8)

Arm 1 (AALL0434 regimen)

ACTIVE COMPARATOR

See detailed description for Arm 1

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Vincristine; Procedure: X-Ray Imaging

Arm 2 (AALL0434 regimen with venetoclax)

EXPERIMENTAL

See detailed description for Arm 2

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Venetoclax; Drug: Vincristine; Procedure: X-Ray Imaging

Arm 3 (AALL0434 regimen with navitoclax)

EXPERIMENTAL

See detailed description for Arm 3

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Biological: Navitoclax; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Vincristine; Procedure: X-Ray Imaging

Arm 4 (AALL0434 regimen with venetoclax and navitoclax)

EXPERIMENTAL

See detailed description for Arm 4

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Biological: Navitoclax; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Venetoclax; Drug: Vincristine; Procedure: X-Ray Imaging

Arm 5 (AALL0434 [no nelarabine])

ACTIVE COMPARATOR

See detailed description for Arm 5

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Vincristine; Procedure: X-Ray Imaging

Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax)

EXPERIMENTAL

See detailed description for Arm 6

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Biological: Navitoclax; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Venetoclax; Drug: Vincristine; Procedure: X-Ray Imaging

Arm 7 (AALL0434 regimen)

ACTIVE COMPARATOR

See detailed description for Arm 7

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Vincristine

Arm 8 (Remission induction with venetoclax and navitoclax)

EXPERIMENTAL

See detailed description for Arm 8

Procedure: Biospecimen Collection; Procedure: Bone Marrow Aspiration; Procedure: Bone Marrow Biopsy; Drug: Calaspargase Pegol; Procedure: Computed Tomography; Drug: Cyclophosphamide; Drug: Cytarabine; Drug: Daunorubicin; Drug: Dexamethasone; Drug: Doxorubicin; Procedure: Echocardiography; Procedure: Lumbar Puncture; Drug: Mercaptopurine; Drug: Methotrexate; Procedure: Multigated Acquisition Scan; Biological: Navitoclax; Drug: Nelarabine; Drug: Pegaspargase; Procedure: Positron Emission Tomography; Drug: Thioguanine; Drug: Venetoclax; Drug: Vincristine; Procedure: X-Ray Imaging

Interventions

Biospecimen Collection PROCEDURE

Undergo blood sample collection

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

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Bone Marrow Aspiration PROCEDURE

Undergo bone marrow aspiration

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Bone Marrow Biopsy PROCEDURE

Undergo bone marrow biopsy

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

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

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 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

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, tomography

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

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, 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

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Cytarabine DRUG

Given IT, 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

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Daunorubicin DRUG

Given IV

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

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Dexamethasone DRUG

Given PO

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, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, TaperDex, Visumetazone, ZoDex

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Doxorubicin DRUG

Given IV

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

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Echocardiography PROCEDURE

Undergo echocardiography

Also known as: EC

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Lumbar Puncture PROCEDURE

Undergo lumbar puncture

Also known as: LP, Spinal Tap

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Mercaptopurine DRUG

Given PO

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 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Methotrexate DRUG

Given IT

Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, 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 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

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, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Navitoclax BIOLOGICAL

Given PO

Also known as: A-855071.0, ABT-263, BcI-2 Family Protein Inhibitor ABT-263

Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 8 (Remission induction with venetoclax and navitoclax)

Nelarabine DRUG

Given IV

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

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Pegaspargase DRUG

Given IV

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

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Positron Emission Tomography PROCEDURE

Undergo PET scan

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, proton magnetic resonance spectroscopic imaging, PT

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

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

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

Venetoclax DRUG

Given PO

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

Arm 2 (AALL0434 regimen with venetoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 8 (Remission induction with venetoclax and navitoclax)

Vincristine DRUG

Given IV

Also known as: LCR, Leurocristine, VCR, Vincrystine

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 7 (AALL0434 regimen); Arm 8 (Remission induction with venetoclax and navitoclax)

X-Ray Imaging PROCEDURE

Undergo X-ray

Also known as: Conventional X-Ray, Diagnostic Radiology, Medical Imaging, X-Ray, Plain film radiographs, Radiographic Imaging, Radiographic imaging procedure (procedure), Radiography, RG, Static X-Ray, X-Ray

Arm 1 (AALL0434 regimen); Arm 2 (AALL0434 regimen with venetoclax); Arm 3 (AALL0434 regimen with navitoclax); Arm 4 (AALL0434 regimen with venetoclax and navitoclax); Arm 5 (AALL0434 [no nelarabine]); Arm 6 (AALL0434 [no nelarabine] + navitoclax & venetoclax); Arm 8 (Remission induction with venetoclax and navitoclax)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Participants must have newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) or T-lineage lymphoblastic lymphoma (T-LBL) based on 2022 World Health Organization (WHO) criteria. Participants with acute leukemia of ambiguous lineage (ALAL), including mixed phenotype acute leukemia (MPAL), are not eligible for this trial
• For T-ALL, immunophenotyping of the blood or marrow lymphoblasts must be performed by flow cytometry to confirm T-cell lineage and exclude ALAL or MPAL. Appropriate lineage-specific antigens include cytoplasmic or surface CD3 for T lineage, myeloperoxidase (MPO) or monocytic antigens (CD11c, CD14, CD64, lysozyme) for myeloid lineage, and CD19, CD20, CD22, CD79a, CD10 and PAX5 for B lineage. For T-LBL, immunohistochemistry on paraffin embedded tissue alone can be used to establish the diagnosis, although flow cytometry is preferred
• NOTE: Systemic chemotherapy must begin within 72 hours of first dose of intrathecal therapy
• Collection of pretreatment blood and bone marrow specimens must be completed within 14 days prior to registration for all participants. If bone marrow is unable to be aspirated and blood blast percentage is at least 5%, additional blood should be collected as instructed in the study calendar
• Participants must not have received prior induction chemotherapy for T-ALL/LBL. Prior treatments with hydroxyurea, all-trans retinoic acid (ATRA), corticosteroids, leukapheresis to reduce peripheral blast count and prevent complications from leukocytosis, and a single dose of intrathecal cytarabine and/or methotrexate with or without steroids are permitted
• Participants must discontinue strong CYP3A4 inducers within 7 days prior to registration. Dose adjustments for CYP3A4 inhibitors/inducers during protocol therapy are defined in the protocol
• Participants must be 18-60 years old
• Participants must have Zubrod/Eastern Cooperative Oncology Group (ECOG performance status of 0-2
• Participants must have a complete medical history and physical exam within 28 days prior to registration
• Participants with extramedullary disease at diagnosis must have a CT scan with contrast of chest, neck, abdomen, pelvis, or whole body to obtain baseline values within 28 days prior to registration
• Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN). Participants with history of Gilbert's disease or leukemia involving the liver must have total bilirubin ≤ 5 x institutional ULN within 7 days prior to registration
• Aspartate aminotransferase (AST)/ Alanine aminotransferase (ALT) Both must be ≤ 3 × institutional ULN unless related to leukemia involving the liver
• Participants must have a serum creatinine 1.5 ≤ the ULN OR measured OR calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault Formula. This specimen must have been drawn and processed within 7 days prior to registration
• Participants must have a lumbar puncture to determine CNS involvement of ALL within 14 days prior to registration. Intrathecal cytarabine and/or methotrexate administered prior to study registration may count as the first dose of intrathecal therapy required as part of protocol therapy
• Participants must have cardiac ejection fraction \>= 50% by MUGA or 2-D echocardiogram within 28 days before registration. Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, must have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants must be class 2B or better

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

MeSH Terms

Conditions

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Specimen Handling; Biopsy; calaspargase pegol; Asparaginase; Cyclophosphamide; Cytarabine; Daunorubicin; Dexamethasone; Calcium Dobesilate; auricularum; dexamethasone acetate; dexamethasone 21-phosphate; Doxorubicin; Spinal Puncture; Mercaptopurine; azathiopurine; Methotrexate; merphos; navitoclax; nelarabine; pegaspargase; Magnetic Resonance Spectroscopy; Thioguanine; venetoclax; Vincristine; X-Rays; Phantoms, Imaging

Condition Hierarchy (Ancestors)

Precursor Cell Lymphoblastic Leukemia-Lymphoma; 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; Cytodiagnosis; Cytological Techniques; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Amidohydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; 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; Diagnostic Techniques, Neurological; Punctures; Therapeutics; Sulfhydryl Compounds; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Aminopterin; Pterins; Pteridines; Spectrum Analysis; Chemistry Techniques, Analytical; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Equipment and Supplies

Study Officials

• Kristen M O'Dwyer

  SWOG Cancer Research Network

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: January 17, 2024
• First Posted: January 18, 2024
• Study Start: August 9, 2024
• Primary Completion (Estimated): September 22, 2026
• Study Completion (Estimated): September 22, 2026
• Last Updated: May 17, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share