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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 L

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

    Detailed Summary:

    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
    • 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Block A Minimal Residual Disease (MRD) [ Time Frame: At the end of Block A therapy (approximately 5 weeks after start of therapy) ]
    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.
  • Block B Minimal Residual Disease (MRD) [ Time Frame: At the end of Block B therapy (approximately 10 weeks after start of therapy) ]
    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.
  • Block C Minimal Residual Disease (MRD) [ Time Frame: At the end of Block C therapy (approximately 13 weeks after start of therapy) ]
    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.
  • Proportion of relevant toxicities [ Time Frame: At the completion of therapy (up to approximately 5 months after the start of therapy) ]
    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.


Original Secondary Outcome:

  • Block A Minimal Residual Disease (MRD) [ Time Frame: At the end of Block A therapy (approximately 5 weeks after start of therapy) ]
    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.
  • Block B Minimal Residual Disease (MRD) [ Time Frame: At the end of Block B therapy (approximately 10 weeks after start of therapy) ]
    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.
  • Block C Minimal Residual Disease (MRD) [ Time Frame: At the end of Block B therapy (approximately 13 weeks after start of therapy) ]
    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.
  • Proportion of relevant toxicities [ Time Frame: At the completion of therapy (up to approximately 5 months after the start of therapy) ]
    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.


Information By: St. Jude Children's Research Hospital

Dates:
Date Received: July 16, 2015
Date Started: November 23, 2016
Date Completion: April 30, 2019
Last Updated: March 30, 2017
Last Verified: August 2016