Clinical Trials /

Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma

NCT02112916

Description:

This randomized phase III trial compares how well combination chemotherapy works when given with or without bortezomib in treating patients with newly diagnosed T-cell acute lymphoblastic leukemia or stage II-IV T-cell lymphoblastic lymphoma. Bortezomib may help reduce the number of leukemia or lymphoma cells by blocking some of the enzymes needed for cell growth. It may also help chemotherapy work better by making cancer cells more sensitive to the drugs. It is not yet known if giving standard chemotherapy with or without bortezomib is more effective in treating T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.

Related Conditions:
  • T-Cell Acute Lymphoblastic Leukemia
  • T-Cell Lymphoblastic Leukemia/Lymphoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma
  • Official Title: A Phase III Randomized Trial Investigating Bortezomib (NSC# 681239) on a Modified Augmented BFM (ABFM) Backbone in Newly Diagnosed T-Lymphoblastic Leukemia (T-ALL) and T-Lymphoblastic Lymphoma (T-LLy)

Clinical Trial IDs

  • ORG STUDY ID: NCI-2014-00712
  • SECONDARY ID: NCI-2014-00712
  • SECONDARY ID: AALL1231
  • SECONDARY ID: AALL1231
  • SECONDARY ID: U10CA180886
  • SECONDARY ID: U10CA098543
  • NCT ID: NCT02112916

Conditions

  • Acute Lymphoblastic Leukemia
  • Adult T Acute Lymphoblastic Leukemia
  • Childhood T Acute Lymphoblastic Leukemia
  • Stage II Childhood Lymphoblastic Lymphoma
  • Stage II Contiguous Adult Lymphoblastic Lymphoma
  • Stage II Non-Contiguous Adult Lymphoblastic Lymphoma
  • Stage III Adult Lymphoblastic Lymphoma
  • Stage III Childhood Lymphoblastic Lymphoma
  • Stage IV Adult Lymphoblastic Lymphoma
  • Stage IV Childhood Lymphoblastic Lymphoma
  • Untreated Adult Acute Lymphoblastic Leukemia
  • Untreated Childhood Acute Lymphoblastic Leukemia

Interventions

DrugSynonymsArms
Bortezomib[(1R)-3-Methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl)amino]propyl]amino]butyl]boronic Acid, LDP 341, MLN341, PS-341, PS341, VelcadeArm B (combination chemotherapy, bortezomib)
Cyclophosphamide(-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida, Ciclofosfamide, Cicloxal, Clafen, Claphene, CP monohydrate, CTX, CYCLO-cell, Cycloblastin, Cycloblastine, Cyclophospham, Cyclophosphamid monohydrate, Cyclophosphamidum, Cyclophosphan, Cyclophosphane, Cyclophosphanum, Cyclostin, Cyclostine, Cytophosphan, Cytophosphane, Cytoxan, Fosfaseron, Genoxal, Genuxal, Ledoxina, Mitoxan, Neosar, Revimmune, Syklofosfamid, WR- 138719Arm A (combination chemotherapy)
Cytarabine.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, Cytosar-U, Cytosine Arabinoside, Cytosine-.beta.-arabinoside, Cytosine-beta-arabinoside, Erpalfa, Starasid, Tarabine PFS, U 19920, U-19920, Udicil, WR-28453Arm A (combination chemotherapy)
Daunorubicin HydrochlorideCerubidin, Cerubidine, Cloridrato de Daunorubicina, Daunoblastin, Daunoblastina, Daunoblastine, Daunomycin hydrochloride, Daunomycin, hydrochloride, Daunorubicin.HCl, Daunorubicini Hydrochloridum, FI-6339, Ondena, RP-13057, Rubidomycin Hydrochloride, RubilemArm A (combination chemotherapy)
DexamethasoneAacidexam, Adexone, Aknichthol Dexa, Alba-Dex, Alin, Alin Depot, Alin Oftalmico, Amplidermis, Anemul mono, Auricularum, Auxiloson, Baycuten, Baycuten N, Cortidexason, Cortisumman, Decacort, Decadrol, Decadron, 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, Dexamethasonum, Dexamonozon, Dexapos, Dexinoral, Dexone, Dinormon, Fluorodelta, Fortecortin, Gammacorten, Hexadecadrol, Hexadrol, Lokalison-F, Loverine, Methylfluorprednisolone, Millicorten, Mymethasone, Orgadrone, Spersadex, VisumetazoneArm A (combination chemotherapy)
Doxorubicin Hydrochloride5,12-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, Doxorubin, Farmiblastina, FI 106, FI-106, hydroxydaunorubicin, RubexArm A (combination chemotherapy)
EtoposideDemethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213Arm A (combination chemotherapy)
Hydrocortisone Sodium Succinate(11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt, A-Hydrocort, Buccalsone, Corlan, Cortisol Sodium Succinate, Cortop, Efcortelan, Emergent-EZ, Flebocortid, Hidroc Clora, Hycorace, Hydro-Adreson, Hydrocort, Hydrocortisone 21-Sodium Succinate, Hydrocortisone Na Succinate, Kinogen, Nordicort, Nositrol, Sinsurrene, Sodium hydrocortisone succinate, Solu-Cortef, Solu-GlycArm A (combination chemotherapy)
IfosfamideAsta Z 4942, Asta Z-4942, Cyfos, Holoxan, Holoxane, Ifex, IFO, IFO-Cell, Ifolem, Ifomida, Ifomide, Ifosfamidum, Ifoxan, IFX, Iphosphamid, Iphosphamide, Iso-Endoxan, Isoendoxan, Isophosphamide, Mitoxana, MJF 9325, MJF-9325, Naxamide, Seromida, Tronoxal, Z 4942, Z-4942Arm A (combination chemotherapy)
Leucovorin CalciumAdinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Fusilev, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, WellcovorinArm A (combination chemotherapy)
Mercaptopurine3H-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-2785Arm A (combination chemotherapy)
MethotrexateAbitrexate, 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-19039Arm A (combination chemotherapy)
PegaspargaseL-Asparaginase with Polyethylene Glycol, Oncaspar, PEG-Asparaginase, PEG-L-Asparaginase, PEG-L-Asparaginase (Enzon - Kyowa Hakko), PEGLA, Polyethylene Glycol L-Asparaginase, Polyethylene Glycol-L-AsparaginaseArm A (combination chemotherapy)
Thioguanine2-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-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, Tioguanin, Tioguanine, Wellcome U3B, WR-1141, X 27Arm A (combination chemotherapy)
Vincristine SulfateKyocristine, Leurocristine Sulfate, Leurocristine, sulfate, Oncovin, Vincasar, Vincosid, Vincrex, Vincristine, sulfateArm A (combination chemotherapy)

Purpose

This randomized phase III trial compares how well combination chemotherapy works when given with or without bortezomib in treating patients with newly diagnosed T-cell acute lymphoblastic leukemia or stage II-IV T-cell lymphoblastic lymphoma. Bortezomib may help reduce the number of leukemia or lymphoma cells by blocking some of the enzymes needed for cell growth. It may also help chemotherapy work better by making cancer cells more sensitive to the drugs. It is not yet known if giving standard chemotherapy with or without bortezomib is more effective in treating T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma.

Detailed Description

      PRIMARY OBJECTIVES:

      I. To compare event-free survival (EFS) in patients with newly diagnosed T-cell acute
      lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LLy) who are randomized
      to a modified augmented Berlin-Frankfurt-Münster (ABFM) backbone versus bortezomib plus the
      modified ABFM backbone.

      SECONDARY OBJECTIVES:

      I. To determine the safety and feasibility of modifying standard therapy for T-ALL and T-LLy
      based on the results of UKALL 2003, which includes a dexamethasone-based induction,
      additional doses of pegaspargase (PEG-ASP) during induction and delayed intensification (DI),
      and dexamethasone pulses during maintenance therapy.

      II. To determine if prophylactic (presymptomatic) cranial irradiation (CRT) can be safely and
      effectively eliminated in the 85-90% of T-ALL patients classified as standard or intermediate
      risk.

      III. To determine the proportion of end of consolidation (EOC) minimal residual disease (MRD)
      >= 0.1% T-ALL patients who become MRD negative (undetectable by flow cytometry) after
      intensification of chemotherapy, using three high risk (HR) BFM blocks, and to compare EFS
      between the patients who become MRD negative after the three HR BFM blocks and continue on
      chemotherapy with those who continue to have detectable MRD and are eligible for other
      treatment strategies, including hematopoietic stem cell transplant (HSCT). Similarly, to
      compare the EFS between very high risk (induction failure) T-LLy patients treated with HR BFM
      intensification blocks who have partial or complete response (PR or CR) with those who do not
      respond (NR).

      TERTIARY OBJECTIVES:

      I. To investigate the prognostic significance of day 29 bone marrow (BM) MRD in T-LLy
      patients.

      II. To determine if protein expression patterns can predict bortezomib response and drug
      resistance in T-ALL.

      III. To analyze and target relevant signaling pathways in T-ALL blasts, focusing on early T
      cell precursor (ETP) acute lymphoblastic leukemia (ALL).

      OUTLINE: Patients are randomized to 1 of 2 treatment arms.

      INDUCTION ARM A: Patients receive cytarabine intrathecally (IT) at time of diagnostic lumbar
      puncture (if within 72 hours from start of protocol therapy) OR day 1; vincristine sulfate
      intravenously (IV) over 1 minute on days 1, 8, 15, and 22; dexamethasone orally (PO) twice
      daily (BID) on days 1-28 (no taper); daunorubicin hydrochloride IV over 1-15 minutes on days
      1, 8, 15, and 22; pegaspargase IV over 1-2 hours on days 4 and 18; and methotrexate IT on
      days 8 and 29 (and on days 15 and 22 for central nervous system 3 involvement [CNS3] T-ALL
      patients).

      INDUCTION ARM B: Patients receive bortezomib IV on days 1, 4, 8, and 11; and cytarabine,
      vincristine sulfate, dexamethasone, daunorubicin hydrochloride, pegaspargase, and
      methotrexate as in Induction Arm A.

      CONSOLIDATION: Beginning on day 36 from Induction, patients receive methotrexate IT on days
      1, 8, 15, and 22 (days 1 and 8 only for CNS3 T-ALL or CNS3 T-LLy patients); cyclophosphamide
      IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or subcutaneously
      (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD) on days 1-14 and
      29-42; pegaspargase IV over 1-2 hours on days 15 and 43; and vincristine sulfate IV on days
      15, 22, 43, and 50. Patients with persistent testicular disease undergo radiation therapy.

      Patients are then assigned to subsequent therapy according to risk assignment. Patients with
      standard risk (SR) disease receive Interim Maintenance with Capizzi methotrexate (CMTX);
      patients with intermediate risk (IR) disease receive Interim Maintenance with high-dose
      methotrexate (HDMTX), Delayed Intensification, and then Interim Maintenance with CMTX; and
      patients with very high risk (VHR) disease receive 3 HR Intensification Blocks, Delayed
      Intensification, and then Interim Maintenance with CMTX.

      CMTX INTERIM MAINTENANCE: Patients receive vincristine sulfate IV on days 1, 11, 21, 31, and
      41; methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11,
      21, 31, and 41; pegaspargase IV over 1-2 hours on days 2 and 22; and methotrexate IT on days
      1 and 31. The next course (based on risk assignment) begins on day 57 or when blood counts
      recover (whichever occurs later).

      DELAYED INTENSIFICATION ARM A: Patients receive vincristine sulfate IV on days 1, 8, 15, 43,
      and 50; dexamethasone PO BID or IV on days 1-7 and 15-21; doxorubicin hydrochloride IV over
      15 minutes on days, 1, 8, and 15; pegaspargase IV over 1-2 hours on days 4, 18, and 43;
      methotrexate IT on days 1, 29, and 36; cyclophosphamide IV over 30-60 minutes on day 29;
      cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO on days
      29-42. The next course (based on risk assignment) begins on day 64 or when blood counts
      recover (whichever occurs later).

      DELAYED INTENSIFICATION ARM B: Patients receive bortezomib IV on days 1, 4, 15, and 18; and
      vincristine sulfate, dexamethasone, doxorubicin hydrochloride, pegaspargase, methotrexate,
      cyclophosphamide, cytarabine, and thioguanine as in Delayed Intensification Arm A. The next
      course (based on risk assignment) begins on day 64 or when blood counts recover (whichever
      occurs later).

      HDMTX INTERIM MAINTENANCE: Patients receive high-dose methotrexate IV over 24 hours on days
      1, 15, 29, and 43; leucovorin calcium IV or PO on days 3-4, 17-18, 31-32, and 45-46;
      vincristine sulfate IV on days 1, 15, 29, and 43; mercaptopurine PO QD on days 1-56; and
      methotrexate IT on days 1 and 29. The next course (based on randomization assignment) begins
      on day 57 or when blood counts recover (whichever occurs later).

      INTENSIFICATION BLOCK I: Patients receive dexamethasone IV or PO BID on days 1-5; high-dose
      methotrexate IV over 24 hours on day 1; leucovorin calcium IV or PO on days 3-4; vincristine
      sulfate IV on days 1 and 6; cyclophosphamide IV over 1-6 hours on days 2-4; high-dose
      cytarabine IV over 3 hours every 12 hours on day 5; pegaspargase IV over 1-2 hours on day 6;
      and triple IT therapy comprising methotrexate IT, hydrocortisone IT, and cytarabine IT on day
      1. The next course (Intensification Block II) begins on day 22 or when blood counts recover
      (whichever occurs later).

      INTENSIFICATION BLOCK II: Patients receive dexamethasone PO BID or IV on days 1-5; high-dose
      methotrexate IV over 24 hours on day 1; leucovorin calcium PO or IV on days 3-4; vincristine
      sulfate IV on days 1 and 6; ifosfamide IV over 1 hour every 12 hours on days 2-4;
      daunorubicin hydrochloride IV over 30 minutes on day 5; pegaspargase IV over 1-2 hours on day
      6; and triple IT therapy on day 1 as in Intensification Block I. The next course
      (Intensification Block III) begins on day 22 or when blood counts recover (whichever occurs
      later).

      INTENSIFICATION BLOCK III: Patients receive dexamethasone PO BID or IV on days 1-5; high-dose
      cytarabine IV over 3 hours every 12 hours on days 1-2; etoposide IV over 1-2 hours every 12
      hours on days 3-5; pegaspargase IV over 1-2 hours on day 6; and triple IT therapy on day 5 as
      in Intensification Block I. The next course (based on randomization) begins on day 22 or when
      blood counts recover (whichever occurs later).

      MAINTENANCE THERAPY: All patients receive vincristine sulfate IV on days 1, 29, and 57;
      dexamethasone PO BID or IV on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84;
      methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (omit day 29 for SR
      patients during the first 4 courses); methotrexate IT on day 1 (and day 29 during the first 4
      courses for SR patients and during the first 2 courses for IR patients). Patients with CNS3
      IR disease also undergo cranial radiation therapy during the first 4 weeks (course 1).
      Treatment in female patients with T-ALL and patients with T-LLY repeats every 12 weeks for up
      to 2 years from the start of Interim Maintenance (week 119). Treatment in male patients with
      T-ALL repeats every 12 weeks for up to 3 years from the start of Interim Maintenance (week
      171).

      All treatment continues in the absence of disease progression or unacceptable toxicity.

      After completion of study treatment, patients are followed up periodically for up to 10
      years.
    

Trial Arms

NameTypeDescriptionInterventions
Arm A (combination chemotherapy)Active ComparatorPatients receive combination chemotherapy without bortezomib. See Detailed Description.
  • Cyclophosphamide
  • Cytarabine
  • Daunorubicin Hydrochloride
  • Dexamethasone
  • Doxorubicin Hydrochloride
  • Etoposide
  • Hydrocortisone Sodium Succinate
  • Ifosfamide
  • Leucovorin Calcium
  • Mercaptopurine
  • Methotrexate
  • Pegaspargase
  • Thioguanine
  • Vincristine Sulfate
Arm B (combination chemotherapy, bortezomib)ExperimentalPatients receive combination chemotherapy with bortezomib. See Detailed Description.
  • Bortezomib
  • Cyclophosphamide
  • Cytarabine
  • Daunorubicin Hydrochloride
  • Dexamethasone
  • Doxorubicin Hydrochloride
  • Etoposide
  • Hydrocortisone Sodium Succinate
  • Ifosfamide
  • Leucovorin Calcium
  • Mercaptopurine
  • Methotrexate
  • Pegaspargase
  • Thioguanine
  • Vincristine Sulfate

Eligibility Criteria

        Inclusion Criteria:

          -  T-ALL: T-ALL patients must be enrolled on Project Every Child (APEC14B1) prior to
             treatment and enrollment on AALL1231

               -  T-LLy: if Project: Every Child (APEC14B1) is available, T-LLy patients must be
                  enrolled on APEC14B1 prior to treatment and enrollment on AALL1231

          -  Patients must have newly diagnosed T-lymphoblastic leukemia (T-ALL) or T-lymphoblastic
             lymphoma (T-LLy) stages II-IV

               -  Note: a diagnosis of T-ALL is established when leukemic blasts lack
                  myeloperoxidase or evidence of B-lineage derivation (cluster of differentiation
                  [CD]19/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 terminal
                  deoxynucleotidyl transferase (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-LLy 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-LLy defined by the submitting institution will be
                  accepted

          -  All patients and/or their parents or legal guardians must sign a written informed
             consent; assent, when appropriate, will be obtained according to institutional
             guidelines

        Exclusion Criteria:

          -  Patients must not have received any cytotoxic chemotherapy for either the current
             diagnosis of T-ALL, T-L-Ly or for any cancer diagnosis prior to the initiation of
             protocol therapy on AALL1231, 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 initiating induction chemotherapy; prior exposure
                  to ANY steroids that occurred > 28 days before the initiation of protocol therapy
                  does not affect eligibility; the dose of prednisone or methylprednisolone does
                  not affect eligibility

               -  Intrathecal cytarabine (the CNS status must be determined based on a sample
                  obtained prior to administration of any systemic or intrathecal chemotherapy,
                  except for steroid pretreatment) system chemotherapy must begin with 72 hours of
                  this IT therapy; or

               -  600 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 use during sedation to prevent or treat airway edema

          -  Pre-existing >= grade 2 sensory or motor peripheral neurotoxicity

          -  Uncontrolled seizure disorder

          -  Diagnosis of Down syndrome (Trisomy 21)

          -  Patients who are pregnant; a pregnancy test is required for female patients of
             childbearing potential

          -  Lactating females who plan to breastfeed

          -  Sexually active patients of reproductive potential who have not agreed to use an
             effective contraceptive method for the duration of their study participation

          -  Patient has hypersensitivity to bortezomib, boron, or mannitol

          -  Serious medical or psychiatric illness likely to interfere with participation in this
             clinical study

          -  Participation in clinical trials with other investigational agents not included in
             this trial, within 14 days of the start of this trial and within 30 days of any dose
             of bortezomib
      
Maximum Eligible Age:30 Years
Minimum Eligible Age:2 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:EFS between modified ABFM backbone with or without bortezomib in all randomized patients
Time Frame:Up to 10 years
Safety Issue:
Description:Interim monitoring for efficacy and futility will be performed. The study will also be monitored for futility using the method of Freidlin and Korn.

Secondary Outcome Measures

Measure:Cumulative incidence rates
Time Frame:Up to 10 years
Safety Issue:
Description:Compared for isolated CNS, isolated bone marrow, and combined bone marrow relapse between IR patients on the non-bortezomib containing arm on this study (no CRT) with similar patients on AALL0434 (+ CRT).
Measure:EFS
Time Frame:Up to 10 years
Safety Issue:
Description:Compared for isolated CNS, isolated bone marrow, and combined bone marrow relapse between IR patients on the non-bortezomib containing arm on this study (no CRT) with similar patients on AALL0434 (+ CRT).
Measure:EFS between very high risk (VHR) T-ALL patients treated with HR BFM intensification blocks who become MRD negative and those who remain MRD positive at the end of HR Block 3
Time Frame:Up to 10 years
Safety Issue:
Description:The proportion of VHR T-ALL patients with EOC MRD >= 0.1% who become MRD negative (MRD undetectable) after the three high-risk BFM blocks of therapy, will be estimated. EFS for these patients (who continue on chemotherapy) will be compared with those who continue to have detectable MRD and who may receive other treatment options including hematopoietic stem cell transplant. Comparison will be descriptive.
Measure:EFS between VHR T-LLy patients treated with HR BFM intensification blocks who have partial remission or complete remission with those who do not respond
Time Frame:Up to 10 years
Safety Issue:
Description:Comparison will be descriptive.
Measure:Incidence of toxicity associated with modified standard therapy, including dexamethasone and additional pegaspargase as graded by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Time Frame:Up to 10 years
Safety Issue:
Description:Safety data will also be compared between the two arms.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:National Cancer Institute (NCI)

Last Updated

September 4, 2017