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

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.

Conditions

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

Interventions

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.

Sponsors & Collaborators

• Novartis Pharmaceuticals

  collaborator INDUSTRY

• Spectrum Pharmaceuticals, Inc

  collaborator INDUSTRY

• St. Jude Children's Research Hospital

  lead OTHER

Principal Investigators

• Sima Jeha, MD · St. Jude Children's Research Hospital

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-11-23

Primary Completion

2018-03-11

Completion

2018-03-11

FDA Drug

Yes

Countries

• United States

Study Locations