This is a phase-II study to evaluate the efficacy of a salvage regimen in children with relapsed T-cell ALL or lymphoma. Peg-asparaginase, mitoxantrone, intrathecal triples (IT) (intrathecal methotrexate/hydrocortisone/cytarabine) (ITMHA) and dexamethasone are commonly used drugs to treat relapsed or refractory acute lymphocytic leukemia or lymphoma (ALL). In this study, the investigators want to know if adding three drugs called panobinostat, bortezomib and liposomal vincristine (VSLI) to this regimen will result in remission (no signs or symptoms of leukemia or lymphoma). - Panobinostat has been approved by the FDA for treating adults with multiple myeloma, but it has not been approved for use in children and has not been given together with the other drugs used in this study. It has not been widely studied in children. - VSLI has been approved by the FDA for adults with relapsed or refractory ALL, but has not yet been approved for treating children with leukemia or lymphoma. - Bortezomib has been approved by the FDA for treating adults with a cancer called multiple myeloma and adults with relapsed mantle cell lymphoma; it has not been approved for treating children. PRIMARY OBJECTIVE: - To estimate the complete remission (CR) rate for patients with T-cell lymphoblastic leukemia and lymphoma in first relapse. SECONDARY OBJECTIVES: - To evaluate minimal residual disease (MRD) levels at end of each block of therapy. - To describe the toxicities of vincristine sulfate liposome injection (VSLI) when used in combination with chemotherapy and bortezomib.
Name: Dexamethasone
Description: Given orally (PO).Type: DrugStudy Participants
Name: Panobinostat
Description: Given PO.Type: DrugStudy Participants
Name: Liposomal vincristine
Description: For intravenous (IV) use only.Type: DrugStudy Participants
Name: Mitoxantrone
Description: Given IV.Type: DrugStudy Participants
Name: Peg-asparaginase
Description: Given IV or intramuscularly (IM). In case of allergy or intolerance to Peg-asparaginase, Erwinia L-asparaginase (Erwinase®) will be used. Erwinia L-asparaginase is given by either IV or IM injection.Type: DrugStudy Participants
Name: Bortezomib
Description: Given by IV push over 3 to 5 seconds. For IV use only.Type: DrugStudy Participants
Name: Intrathecal Triples
Description: Given IT as ITMHA.Type: DrugStudy Participants
Name: High-dose methotrexate
Description: Given intrathecally (IT) or IV.Type: DrugStudy Participants
Name: 6-Mercaptopurine
Description: Given PO at consistent time each day.Type: DrugStudy Participants
Name: High-dose cytarabine
Description: Given IT or IV.Type: DrugStudy Participants
Name: Nelarabine
Description: Given IVType: DrugStudy Participants
Name: Cyclophosphamide
Description: Given IV.Type: DrugStudy Participants
Name: Etoposide
Description: Given IV. In case of etoposide reactions, IV etoposide phosphate (Etopophos®) will be used.Type: DrugStudy Participants
Name: Clofarabine
Description: Given IV. Clofarabine will be given instead of nelarabine for patients with B-lymphoblastic leukemia and lymphoma in stratum II.Type: DrugStudy Participants
Description: All participants who start re-induction Block A therapy are considered evaluable. Any patient who at any time point achieves CR and goes to transplant is considered as a success; or any patient who successfully reaches the end of block C and achieves/remains in CR is considered a success; all other cases are considered as failure.
Measure: Complete Remission (CR) Rate Time: At the end of each remission re-induction block C (approximately 13 weeks after start of therapy)Description: MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.
Measure: Block A Minimal Residual Disease (MRD) Time: At the end of Block A therapy (approximately 5 weeks after start of therapy)Description: MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.
Measure: Block B Minimal Residual Disease (MRD) Time: At the end of Block B therapy (approximately 10 weeks after start of therapy)Description: MRD will be studied after each cycle of therapy. MRD is considered as positive (i.e., prevalent) if its level is ≥0.01% for ALL. The prevalence of MRD at end of each cycle is defined as proportion of MRD positives; we will estimate these proportions with point and interval estimates.
Measure: Block C Minimal Residual Disease (MRD) Time: At the end of Block C therapy (approximately 13 weeks after start of therapy)Description: The toxicities of liposomal vincristine (VSLI) when used in combination with chemotherapy will be evaluated. Proportions (probabilities) of relevant toxicities will be estimated with point and interval estimates.
Measure: Proportion of Relevant Toxicities Time: At the completion of therapy (up to approximately 5 months after the start of therapy)Single Group Assignment
There is one SNP
Additional ITs on Days 10 and 17 for patients with central nervous system (CNS) 2, 3 or traumatic tap with blasts Block B: approximately 5 weeks - High-dose methotrexate 8 g/m^2 IV over 24 hours (will not be given to patients with prior cranial irradiation) Day 1 - 6-mercaptopurine 50 mg/m^2 PO days 1-14 - ITMHA Day 1 - High-dose cytarabine 3 g/m^2 IV every 12 hours (Q12H) Days 15 and 16 Block C: approximately 3 weeks - Nelarabine 650 mg/m^2/day IV Days 1-5 (Clofarabine 40 mg/m^2/day IV Days 1-5 will be given instead of nelarabine for patients with B-lymphoblastic leukemia and lymphoma in stratum II) - Cyclophosphamide 300 mg/m^2 IV Days 1-5 - Etoposide 100 mg/m^2/day IV Days 1-5 Response evaluation is performed after the end of each treatment block. --- Q12H ---