Ignite Creation Date:
2025-12-24 @ 4:49 PM
Ignite Modification Date:
2026-01-22 @ 12:32 PM
Study NCT ID:
NCT02518750
Status:
TERMINATED
Last Update Posted:
2019-04-03
First Post:
2015-07-16
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Re-Induction Therapy for Relapsed Pediatric T-Cell Acute Lymphoblastic Leukemia or Lymphoma
Sponsor:
St. Jude Children's Research Hospital
Organization:
Study Overview
Official Title:
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
Status Verified Date:
2018-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Due to slow accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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.
* 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.
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.
Study Oversight
Has Oversight DMC:
False
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| NCI-2015-00935 | REGISTRY | NCI Clinical Trial Registration Program | View |