Clinical Trial: Immunotherapy With Tacrolimus Resistant EBV CTL for Lymphoproliferative Disease After Solid Organ Transplant

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: Immunotherapy With Tacrolimus Resistant EBV CTL for Lymphoproliferative Disease After Solid Organ Transplant

Brief Summary: This is an open label, non-randomised, multicentre Phase I to determine the safety of tacrolimus-resistant autologous EBV-specific cytotoxic T-cells (EBV CTL) and compare their expansion/persistence with control EBV CTL in solid organ transplant patients with post-transplant lymphoproliferative disease (PTLD). Each patient will receive an infusion of two ATIMPs - autologous EBV CTL retrovirally transduced with (a) a calcineurin mutant (CNA12) that confers resistance to tacrolimus and (b) a control calcineurin mutant (CNA8).

Detailed Summary:

This is a multi-centre, non-randomised, open label Phase 1 clinical trial of Advanced Therapy Investigational Medicinal Products (ATIMPs) in adult and paediatric (age 1-70 years) solid organ transplant recipients with histologically proven B-lineage EBV+ post-transplant lymphoproliferative disease (PTLD).

The ATIMPs for this study are autologous EBV CTL transduced with the (a) the retroviral vector SFG-CNA12 encoding a calcineurin A mutant (CNA12) that confers resistance to tacrolimus and (b) the retroviral vector SFG-CNA8 encoding a control calcineurin A mutant (CNA8).

Following informed consent and registration to the trial, patients will undergo an unstimulated leucapheresis for generation of both ATIMPs. Patients will receive an equal dose of each ATIMP (107 CNA8+ or CNA12+ CTL/m2) which will be administered intravenously.

Other immunosuppressants (e.g. MMF) will be reduced, but tacrolimus will be maintained at therapeutic levels.The trial will evaluate the safety of the ATIMPs in organ transplant recipients developing EBV+ PTLD and compare the persistence and frequency of circulating CNA12 and CNA8 CTL in the peripheral blood.

Our hypothesis is that in the presence of ongoing immunosuppression with tacrolimus, CNA12 CTL will show preferential expansion and prolonged persistence compared with CNA8 CTL. If successful this will result in durable clearance of PTLD without the need to reduce tacrolimus, thus reducing the risk of graft rejection.

Patients will be followed up regularly during the interventional phase of the study until 1 year post EBV CTL infusion. During the long-term follow-up phase of the study (from 1-5 years post EBV CTL infusion) patients will be followed
Sponsor: University College, London

Current Primary Outcome:

• Toxicity at 6 weeks post infusion [ Time Frame: 6 weeks ]
  Toxicity as assessed by NCI Common toxicity criteria within 6 weeks of infusion
• Persistence and frequency of circulating EBV CTL [ Time Frame: 12 months ]
  Persistence and frequency of circulating EBV CTL transduced with CNA12 compared with control vector CNA8 in the peripheral blood

Original Primary Outcome:

• Toxicity [ Time Frame: 6 weeks ]
  Toxicity as assessed by NCI Common toxicity criteria within 6 weeks of infusion
• Efficacy [ Time Frame: 12 months ]
  Persistence and frequency of circulating EBV CTL transduced with CNA12 compared with control vector CNA8 in the peripheral blood

Current Secondary Outcome:

• Disease response [ Time Frame: 6 weeks ]
  Disease response at 6 weeks
• Relapse rate [ Time Frame: 2 years ]
  Relapse rate at 1 and 2 years
• Disease free survival [ Time Frame: 2 years ]
  Disease free survival at 1 and 2 yrs
• Organ graft Rejection [ Time Frame: 2 years ]
  Organ graft Rejection at 1 and 2 yrs

Original Secondary Outcome: Same as current

Information By: University College, London

Dates:
Date Received: April 24, 2017
Date Started: September 15, 2017
Date Completion: September 15, 2024
Last Updated: May 10, 2017
Last Verified: May 2017