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
Condition: Adult T Acute Lymphoblastic Leukemia; Ann Arbor Stage II Adult Lymphoblastic Lymphoma; Ann Arbor Stage II Childhood Lymphoblastic Lymphoma; Ann Arbor Stage III Adult Lymphoblastic Lymphoma; Ann Arbor Stage III Childhood Lymphoblastic Lymphoma; Ann Arbor Stage IV Adult Lymphoblastic Lymphoma; Ann Arbor Stage IV Childhood Lymphoblastic Lymphoma; Childhood T Acute Lymphoblastic Leukemia
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Lymphoma, Non-Hodgkin; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Intervention: Bortezomib; Cyclophosphamide; Cytarabine; Daunorubicin; Daunorubicin Hydrochloride; Dexamethasone; Doxorubicin; Doxorubicin Hydrochloride; Etoposide; Hydrocortisone Sodium Succinate; Ifosfamide; Leucovorin Calcium; Mercaptopurine; Methotrexate; Pegaspargase; Radiation Therapy; Thioguanine; Vincristine; Vincristine Sulfate
Intervention description: Given IV; Given IV; Given IT, IV, or SC; Given IV; Given IV; Given PO or IV; Given IV; Given IV; Given IV; Given IT; Given IV; Given PO or IV; Give PO; Given IT, IV, or PO; Given IV; Undergo radiation therapy; Given PO; Given IV; Given IV
Intervention MeSH terms: Calcium, Dietary; Leucovorin; Folic Acid; Cytarabine; Dexamethasone; Dexamethasone acetate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Cyclophosphamide; Ifosfamide; Isophosphamide mustard; Doxorubicin; Liposomal doxorubicin; Methotrexate; Etoposide; Vincristine; Etoposide phosphate; Bortezomib; Daunorubicin; Asparaginase; Mercaptopurine; Podophyllotoxin; Pegaspargase; Thioguanine; BB 1101; Calcium; 2-Aminopurine; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 847.0
Sex: All
Minimum age: 1 Year
Maximum age: 30 Years
Healthy volunteers: No

Summary:

      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 newly diagnosed T-cell acute lymphoblastic leukemia and T-cell
      lymphoblastic lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  T-ALL: T-ALL patients must be enrolled on AALL08B1 or Project:EveryChild (APEC14B1, if
             open for the classification of ALL patients) prior to treatment and enrollment on
             AALL1231

          -  All patients must be > 1 and < 31 years of age

          -  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

               -  Pretreatment with hydroxyurea; 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;
                       inhalation steroids and topical steroids are not considered pretreatment

          -  Pre-existing >= grade 2 sensory or motor peripheral neurotoxicity

          -  Uncontrolled seizure disorder

          -  Diagnosis of Down syndrome (Trisomy 21)

          -  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

          -  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