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

NCT03131934 | Active Not Recruiting Early Phase 1 DMC

• 1 other identifier: UCL/16/0529
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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).

Conditions

Post-transplant Lymphoproliferative Disease; Transplant-Related Hematologic Malignancy

Outcome Measures

Primary Outcomes (2)

• Toxicity at 6 weeks post infusion

  Toxicity as assessed by NCI Common toxicity criteria within 6 weeks of infusion

  6 weeks

• Persistence and frequency of circulating EBV CTL

  Persistence and frequency of circulating EBV CTL transduced with CNA12 compared with control vector CNA8 in the peripheral blood

  12 months

Secondary Outcomes (4)

• Disease response

  6 weeks

• Relapse rate

  2 years

• Disease free survival

  2 years

• Organ graft Rejection

  2 years

Study Arms (1)

Autologous EBV-CTL transduced with SFG-CNA12/SFG-CNA8

EXPERIMENTAL

All patients will receive the autologous EBV CTL retrovirally transduced with with (a) a calcineurin mutant (CNA12) that confers resistance to tacrolimus and (b) a control calcineurin mutant (CNA8). For each patient two ATIMPs will be generated: * Autologous EBV-specific cytotoxic T-cells (CTL) transduced with the retroviral vector SFG-CNA12 * Autologous EBV-specific cytotoxic T-cells (CTL) transduced with the control retroviral vector SFG-CNA8 An equal dose (10x7/m2) of CNA12+ EBV CTL and CNA8+ EBV CTL will be administered intravenously on day 0. While awaiting ATIMP generation, patients may receive a single dose of Rituximab and other immunosuppressants (e.g. MMF) will be reduced, but tacrolimus will be maintained at therapeutic levels.

Biological: Autologous EBV-CTL transduced with vector SFG-CNA12; Biological: Autologous EBV-CTL transduced with control vector SFG-CNA8; Procedure: Leucapheresis

Interventions

Autologous EBV-CTL transduced with vector SFG-CNA12 BIOLOGICAL

Autologous EBV-specific cytotoxic T-cells (CTL) transduced with the retroviral vector SFG-CNA12 conferring resistance to tacrolimus

Autologous EBV-CTL transduced with SFG-CNA12/SFG-CNA8

Autologous EBV-CTL transduced with control vector SFG-CNA8 BIOLOGICAL

Autologous EBV-specific cytotoxic T-cells (CTL) transduced with the control retroviral vector SFG-CNA8

Autologous EBV-CTL transduced with SFG-CNA12/SFG-CNA8

Leucapheresis PROCEDURE

Patients will undergo an unstimulated leucapheresis to isolate the required immune cells to produce the EBV-CTLs

Autologous EBV-CTL transduced with SFG-CNA12/SFG-CNA8

Eligibility Criteria

• Age: 1 Year - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult and paediatric (age 1-70 years) solid organ transplant recipients with histologically proven B-lineage EBV+ post-transplant lymphoproliferative disease (PTLD) either de novo or resistant to Rituximab
• EBV viraemia at enrolment
• On immunosuppression with tacrolimus
• Agreement to have a pregnancy test and use of contraception for duration of trial (if applicable)
• Written informed consent

You may not qualify if:

• Fulminant disease
• Requirement for supplemental oxygen
• Burkitt's lymphoma/Mature B-acute lymphoblastic leukaemia with IgH-Myc rearrangement
• T-lineage PTLD
• Bilirubin \> 3 x upper limit of normal
• Creatinine \> 3 x upper limit of normal
• Active hepatitis B, C or HIV infection
• Women who are pregnant or breast-feeding
• ECOG performance score ≥ 4
• Inability to tolerate leucapheresis

Sponsors & Collaborators

• University College, London: lead
• Genetix Biotherapeutics Inc.: collaborator

Study Sites (2)

Great Ormond Street Hospital

London, United Kingdom

Location

King's College Hospital

London, United Kingdom

Location

MeSH Terms

Interventions

Leukapheresis

Intervention Hierarchy (Ancestors)

Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Prof. Persis Amrolia

  Great Ormond Street Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 24, 2017
• First Posted: April 27, 2017
• Study Start: May 31, 2019
• Primary Completion: June 30, 2020
• Study Completion: May 15, 2025
• Last Updated: May 17, 2024

Record last verified: 2024-05

Locations

GB (2)