Study of Donor Derived, Multi-virus-specific, Cytotoxic T-Lymphocytes for Relapsed/Refractory Neuroblastoma
Condition: Neuroblastoma
MeSH terms: Neuroblastoma
Intervention: GD2 CAR modified Tri-virus specific cytotoxic t-cells
Intervention description: 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
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 5.0
Sex: All
Minimum age: 18 Months
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Neuroblastoma; Relapsed; Refractory

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Allogeneic transduced tV-CTLs with >15% expression of 14g2a.zeta chimeric antigen
             receptor

          -  Patient or responsible person must be able to understand and sign a permission/assent
             or consent form for infusion

          -  Age 18 months through 17 years at time of relapse/progression

          -  Life expectancy >8weeks

          -  Karnofsky score 60% or greater if 10 yrs old or older. Lansky score 60% or greater if
             under 10 yrs old

          -  Patient must be HIV negative

          -  ANC >500

          -  Pulse ox>90% on room air

          -  AST/ALT/direct bili <5x upper limit of normal

          -  Recovered from toxic effects of all prior chemotherapy

          -  Absence of human/anti-mouse antibody (HAMA) (patients who have received prior therapy
             with murine antibodies)

          -  >50% donor engraftment

        Exclusion Criteria:

          -  Patient pregnant or lactating or refuses birth control methods

          -  HIV positive

          -  Uncontrolled intercurrent infection

          -  Renal failure (creatinine clearance <40ml/min/1.73m2)

          -  Active hepatitis or cirrhosis with bilirubin, AST, ALT >5xnormal

          -  Rapidly progressive disease

          -  Currently receiving any investigational drugs

          -  Tumor potentially causing airway obstruction

          -  Cardiomegaly or bilateral pulmonary infiltrates on CXR

          -  Receiving >0.25mg/kg/day methylprednisolone or equivalent systemic steroid. Topical
             steroid therapy is acceptable

          -  Receiving more than one lymphocyte inhibiting agent (ex. Tacrolimus/CSA and MMF or
             other similar agent

          -  Patients relapsing or progressing before the age of 18 months from Stage I/II disease,
             and/or those who, in the opinion of their oncologist, may benefit from further
             conventional therapy

          -  Donor lymphocyte infusion in last 28 days

          -  Evidence of GvHD greater than or equal to grade 2