A Phase III Randomized Trial Investigating Bortezomib on a Modified Augmented BFM Backbone in Newly Diagnosed T-Lymphoblastic Leukemia and T-Lymphoblastic Lymphoma

Basic eligibility criteria:
Please contact the study coordinator for additional eligibility information.

3.2.1 INCLUSION CRITERIA
a. Classification Study:
• T-ALL: T-ALL patients must be enrolled on AALL08B1 or 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
b. Age at Diagnosis: All patients must be > 1 and < 31 years of age.
c. Diagnosis: Patients must have newly diagnosed T-Lymphoblastic Leukemia (T-ALL) or T-Lymphoblastic Lymphoma (T-LLy) Stages II-IV (see Appendix VIII).
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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 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. See pathologic diagnosis recommendation in Section 13.4.
d. Informed consent: 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
3.2.2 EXCLUSION CRITERIA
a. Prior Therapy: 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; 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.
b. Peripheral neurotoxicity: Pre-existing ? grade 2 sensory or motor peripheral neurotoxicity.
c. Seizures disorder: Uncontrolled seizure disorder
d. Diagnosis of Down syndrome (Trisomy 21) e. 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.
f. Lactating females who plan to breastfeed.
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g. Sexually active patients of reproductive potential who have not agreed to use an effective
contraceptive method for the duration of their study participation.
h Patient has hypersensitivity to bortezomib, boron, or mannitol.
i Serious medical or psychiatric illness likely to interfere with participation in this clinical study.
j 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.