Study of Donor Derived, Multi-virus-specific, Cytotoxic T-Lymphocytes for Relapsed/Refractory Neuroblastoma
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a single-center, investigator-initiated, single-arm, pilot study of post-allogeneic
      transplant, adoptive immunotherapy for the treatment of patients with relapsed/refractory
      neuroblastoma expressing the mesenchymal tumor marker GD2. Three patients will be treated.
      The study will focus on the safety and efficacy of allogeneic, donor derived viral specific
      cytotoxic T-lymphocytes, retrovirally transduced to express a chimeric antigen receptor
      specific for disialoganglioside, GD2, expressed on neuroblastoma.
    

Detailed description: 
      Neuroblastoma (NB) is the most common extracranial tumor of childhood and prognosis for
      patients with relapsed or refractory disease is < 10% and there is no standard therapy for
      these patients. Research toward immunotherapeutic agents has intensified as monoclonal
      antibody targeting GD2, when incorporated into upfront NB therapy, prolongs survival.
      Allogeneic Hematopoietic stem cell transplantation (HSCT) has been utilized in patients with
      NB with evidence of a graft versus tumor (GVT) effect but transplant related mortality (TRM)
      has nullified the survival benefit. In an effort to harness the GVT effect of allogeneic
      transplant and lower TRM, harvested viral specific cytotoxic T-cells from the donor will be
      infused early post-HSCT to the HSCT recipient to shorten the recovery of immunity toward the
      most significant viral infections. The investigators will also retrovirally transduce the
      viral specific CTL with a chimeric antigen receptor (CAR) gene complex such that the tV-CTL
      can expand, via their native T-cell receptors in response to viral infections post-HSCT and
      carry the capability of killing tumor cells through their transduced receptor which, on the
      extracellular component of the CAR, has specificity for GD2 expressed on the surface of NB.
      In essence, the investigators intend to take the specificity of the monoclonal antibody to
      GD2, already utilized in therapy for NB, and combine this specificity with the cytotoxicity
      of T-cells to target NB. The investigators hypothesize that the infusion will be safe and
      viral specificity of the tV-CTL will provide long term immunity to both viral infections and
      the investigators will see anti-tumor effects.
    

Intervention name(s): GD2 CAR modified Tri-virus specific cytotoxic t-cells
Intervention type(s): Biological
Intervention description(s): This is a feasibility study to assess safety of an infusion of chimeric-antigen receptor gene modified allogeneic virus specific T lymphocytes after reduced intensity allogeneic stem cell transplant. Three patients were treated and safety was evaluated. Patients received a single infusion of 2x10e6/m2 donor derived, GD2 CAR modified, tri-virus specific CTL performed 30-120 days after allogeneic stem cell transplantation
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Neuroblastoma; Relapsed; Refractory