NCT02518750

Re-Induction Therapy for Relapsed Pediatric T-Cell Acute Lymphoblastic Leukemia or Lymphoma

A Phase II Study Incorporating Panobinostat, Bortezomib and Liposomal Vincristine Into Re-Induction Therapy for Relapsed Pediatric T-Cell Acute Lymphoblastic Leukemia or Lymphoma

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 3 (actual)
• Sponsor: St. Jude Children's Research Hospital · Academic / Other
• Sex: All
• Age: 21 Years
• Healthy volunteers: Not accepted

Summary

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.

Detailed description

This is a study of re-induction therapy that will comprise of three blocks of multi-agent chemotherapy. CR will be evaluated following each block of therapy. All patients will be candidates for hematopoietic stem cell transplant (HSCT) once they achieve negative minimal residual disease (MRD). If patients cannot proceed to HSCT following Block A, they will continue therapy on Block B and Block C until ready for HSCT. Three Block Induction: Block A: approximately 5 weeks * Dexamethasone 10 mg/m\^2/day orally (PO) Days 1-8, 15-22 (Total 16 days) * Panobinostat 24 mg/m\^2/dose PO Day 2,4,6 * Liposomal vincristine (VSLI) 2.25 mg/m\^2 no cap intravenously (IV) on Days 7, 14, 21, 28 * Mitoxantrone 10 mg/m\^2 IV Day 7,14 (In the absence of peripheral blasts, Day 14 Mitoxantrone will be given if WBC ≥1000 and ANC ≥300) * Peg-asparaginase 2500 units/m\^2 on Days 9,23 * Bortezomib 1.3 mg/m\^2 IV Days 16, 19, 23, 26 * Intrathecal Triples (IT) (intrathecal methotrexate/hydrocortisone/cytarabine) (ITMHA) Days 1, 7, 14, 21, 28. 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. All patients should proceed to hematopoietic stem cell transplantation (HSCT) after achieving negative minimal residual disease (MRD) when a suitable donor is identified. Patients could continue on Block B and Block C if not ready for HSCT. If after completion of Block C, MRD is persistently positive, the plan will be discussed with the principal investigator and co-principal investigator and the transplant team. Enrollment on ongoing natural killer (NK) cell studies will be considered. For patients who require a second transplant, HAP3R (another clinical trial at St. Jude Children's Research Hospital) may be an option. Donor will be selected according to institutional practices and transplant regimens will be used according to institutional HSCT protocols and guidelines.

Conditions

• Acute Lymphoblastic Leukemia
• Lymphoma, Non-Hodgkin's
• Leukemia, T-Cell
• Leukemia, B-Cell

Interventions

Type	Name	Description
DRUG	Dexamethasone	Given orally (PO).
DRUG	Panobinostat	Given PO.
DRUG	Liposomal vincristine	For intravenous (IV) use only.
DRUG	Mitoxantrone	Given IV.
DRUG	Peg-asparaginase	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.
DRUG	Bortezomib	Given by IV push over 3 to 5 seconds. For IV use only.
DRUG	Intrathecal Triples	Given IT as ITMHA.
DRUG	High-dose methotrexate	Given intrathecally (IT) or IV.
DRUG	6-Mercaptopurine	Given PO at consistent time each day.
DRUG	High-dose cytarabine	Given IT or IV.
DRUG	Nelarabine	Given IV
DRUG	Cyclophosphamide	Given IV.
DRUG	Etoposide	Given IV. In case of etoposide reactions, IV etoposide phosphate (Etopophos®) will be used.
DRUG	Clofarabine	Given IV. Clofarabine will be given instead of nelarabine for patients with B-lymphoblastic leukemia and lymphoma in stratum II.

Timeline

• Start date: 2016-11-23
• Primary completion: 2018-03-11
• Completion: 2018-03-11
• First posted: 2015-08-10
• Last updated: 2019-04-03
• Results posted: 2019-04-03

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study