CMV TCR Gene Therapy Trial

CMV TCR Gene Therapy: A Phase I Safety, Toxicity and Feasibility Study of Adoptive Immunotherapy with CMV TCR-transduced Donor-derived T cells for Recipients of Allogeneic Haematopoietic Stem Cell Transplantation. - CMV TCR Gene Therapy (CMV TCR-001)

Status

Active, not recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2008-006649-18-GB

Enrollment

Registered

2011-11-22

Start date

2011-11-16

Completion date

Unknown

Last updated

2020-07-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

CMV reactivation/infection in post allogeneic haematopoietic stem cell transplant recipients. Allo-HSCT being performed for underlying haematological malignancy (eg, AML, ALL, NHL, Hodgkin Lymphoma, etc). MedDRA version: 19.0 Level: LLT Classification code 10067859 Term: Allogenic stem cell transplantation System Organ Class: 100000004865

Interventions

Product Name: CMV TCR-transduced donor T cells Pharmaceutical Form: Solution for infusion

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Inclusion Criteria (Recipient): 1. Age: 18-65 years (inclusive) 2. Recipients of HLA-matched sibling Allo-HSCT for underlying haematological malignancies as per national and institutional guidelines. 3. HLA-A*0201 positive 4. CMV seropositive (anti-CMV IgG detectable pre-transplant) 5. Meets all other recipient criteria for Allo-HSCT as per institutional guidelines. Inclusion Criteria (Donors) 1. Pre-selected HLA-matched sibling stem cell donor (as per institutional criteria) 2. Age: 16 years or older (inclusive) 3. HLA-A*0201 positive 4. CMV seronegative (no anti-CMV IgG detectable) For further details of inclusion and exclusion criteria please see Clinical Trial Protocol. Patients will be recruited to the study during their pre-transplant consultation and medical. Participants will only be eligible for the study if they are: (i) HLA-A*0201 positive (the TCR is HLA-A*0201 restricted and CMV pp65-specific) and (ii) CMV seropositive (CMV IgG detected) and their donor is: (i) an HLA-matched sibling/family member and (ii) CMV seronegative (CMV IgG not detected). All participants will be required to give signed, informed consent. A detailed explanation of the study rationale and risks will be given by the relevant PI. All patients will receive a patient information sheet and be given time to discuss the study with family and friends. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0

Exclusion criteria

Exclusion criteria: (i) Pregnant or lactating women (ii) Co-existing medical problems that would place the patient at significant risk of death due to GVHD or its sequelae (iii) HIV infection And to be assessed prior to CMV-specific T cell infusion (for confirmation prior to product release): (i) Active acute GVHD > Grade I (ii) Concurrent use of systemic corticosteroids (iii) Organ dysfunction as measured by ii. creatinine > 200 uM/l iii. bilirubin > 50 uM/l iv. ALT > 3x upper limit of normal

Design outcomes

Primary

Measure	Time frame
Main Objective: The proposed study will test the feasibility of generating donor-derived cytomegalo virus (CMV)-specific T cells via the ex vivo introduction of a CMV-specific T cell receptor using a GMP grade retroviral vector. It will also determine the safety, toxicity (side effects) and efficacy of CMV TCR-transduced T cells used for the pre-emptive treatment of CMV reactivation following HLA-matched sibling Allo-Haematopoietic Stem Cell Transplantation. Primary Objectives: (i) Evaluate the feasibility of retroviral-mediated TCR gene transfer to generate CMV-specific T cells from CMV seronegative donors; (ii) Evaluate the safety, toxicity and side effects of pre-emptive CMV TCR-transduced donor-derived T cells for immunotherapy after Allo-HSCT, where donors are CMV seronegative. Primary Endpoints: (i) Document transduction efficiency and TCR expression on TCR-transduced T cells; (ii) Identify organ toxicities and other side effects. We propose that CMV TCR-transduced T cells, generated from ;Secondary Objective: Secondary Objectives: (i) Evaluate the efficacy of CMV TCR-transduced T cells in the pre-emptive treatment of CMV reactivation; (ii) Evaluate the effect of CMV TCR-transduced T cells on immune reconstitution and Graft-versus Host Disease (GvHD) after Allo-HSCT; (iii) Determine the persistence of CMV TCR-transduced T cells in the recipients; (iv) Evaluate for long-term complications related to retroviral gene therapy, as per Gene Therapy Advisory Committee Guidelines. Secondary Endpoints: (i) Document CMV-specific immune responses of TCR-transduced T cells pre- and post-infusion using in vitro functional assays such as intracellular cytokine secretion, elispot, proliferation and cytotoxicity assays; (ii) Document anti-CMV responses post infusion of CMV TCR-transduced T cells using serial quantitative PCR for viral copy numbers in peripheral blood; (iii) Document incidence and severity of GvHD post infusion of CMV TCR-transduced T cells follow	—

Measure

Time frame

Main Objective: The proposed study will test the feasibility of generating donor-derived cytomegalo virus (CMV)-specific T cells via the ex vivo introduction of a CMV-specific T cell receptor using a GMP grade retroviral vector. It will also determine the safety, toxicity (side effects) and efficacy of CMV TCR-transduced T cells used for the pre-emptive treatment of CMV reactivation following HLA-matched sibling Allo-Haematopoietic Stem Cell Transplantation. Primary Objectives: (i) Evaluate the feasibility of retroviral-mediated TCR gene transfer to generate CMV-specific T cells from CMV seronegative donors; (ii) Evaluate the safety, toxicity and side effects of pre-emptive CMV TCR-transduced donor-derived T cells for immunotherapy after Allo-HSCT, where donors are CMV seronegative. Primary Endpoints: (i) Document transduction efficiency and TCR expression on TCR-transduced T cells; (ii) Identify organ toxicities and other side effects. We propose that CMV TCR-transduced T cells, generated from ;Secondary Objective: Secondary Objectives: (i) Evaluate the efficacy of CMV TCR-transduced T cells in the pre-emptive treatment of CMV reactivation; (ii) Evaluate the effect of CMV TCR-transduced T cells on immune reconstitution and Graft-versus Host Disease (GvHD) after Allo-HSCT; (iii) Determine the persistence of CMV TCR-transduced T cells in the recipients; (iv) Evaluate for long-term complications related to retroviral gene therapy, as per Gene Therapy Advisory Committee Guidelines. Secondary Endpoints: (i) Document CMV-specific immune responses of TCR-transduced T cells pre- and post-infusion using in vitro functional assays such as intracellular cytokine secretion, elispot, proliferation and cytotoxicity assays; (ii) Document anti-CMV responses post infusion of CMV TCR-transduced T cells using serial quantitative PCR for viral copy numbers in peripheral blood; (iii) Document incidence and severity of GvHD post infusion of CMV TCR-transduced T cells follow

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Secondary

Measure	Time frame
Secondary end point(s): (i) Document CMV-specific immune responses of TCR-transduced T cells pre- and post-infusion using in vitro functional assays such as intracellular cytokine secretion, elispot, proliferation and cytotoxicity assays; (ii) Document anti-CMV responses post infusion of CMV TCR-transduced T cells using serial quantitative PCR for viral copy numbers in peripheral blood; (iii) Document incidence and severity of GvHD post infusion of CMV TCR-transduced T cells following Allo-HSCT using standardised international criteria; (iv) Perform immune reconstitution studies post infusion of CMV TCR-transduced T cells following Allo-HSCT; (v) Detect persistence of TCR-transduced T cells by Vbeta13 and tetramer staining, PCR for Vbeta13 and TCR vector fragments. ;Timepoint(s) of evaluation of this end point: (i) CMV-specific T cell function: Day -2 (baseline), +7d, +14d, +28d, +6w, +10w, +4m, +5m, +6m, +8m, +10m,+12m, then 6-monthly to 5 yrs (ii) Quantitative CMV PCR at Day -2 (baseline), + 48 hrs, +7d, +14d, then weekly until +6 wks, bi-weekly until + 12 weeks, then +4m, +5m, +6m, +8m, +10m,+12m, then 6-monthly to 5 yrs (iii) GVHD assessments at Day -2, +6hrs, 7d, then weekly until +6 weeks, bi-weekly until + 12 wks, then +4m, +5m, +6m, +8m, +10m,+12m, then 6-monthly to 5 yrs (iv) T cell reconstitution: Day -2 (baseline), +7d, +14d, +28d, +6w, +10w, +4m, +5m, +6m, +8m, +10m, +12m, then 6-monthly to 5 yrs (v) Persistence: Time 0, +6hrs, +24hrs, +48hrs, +72hrs, 7d, then weekly until +6 wks, bi-weekly until + 12 wks, then +4m, +5m, +6m, +8m, +10m, +12m, then 6-monthly to 5 yrs	—

Measure

Time frame

Secondary end point(s): (i) Document CMV-specific immune responses of TCR-transduced T cells pre- and post-infusion using in vitro functional assays such as intracellular cytokine secretion, elispot, proliferation and cytotoxicity assays; (ii) Document anti-CMV responses post infusion of CMV TCR-transduced T cells using serial quantitative PCR for viral copy numbers in peripheral blood; (iii) Document incidence and severity of GvHD post infusion of CMV TCR-transduced T cells following Allo-HSCT using standardised international criteria; (iv) Perform immune reconstitution studies post infusion of CMV TCR-transduced T cells following Allo-HSCT; (v) Detect persistence of TCR-transduced T cells by Vbeta13 and tetramer staining, PCR for Vbeta13 and TCR vector fragments. ;Timepoint(s) of evaluation of this end point: (i) CMV-specific T cell function: Day -2 (baseline), +7d, +14d, +28d, +6w, +10w, +4m, +5m, +6m, +8m, +10m,+12m, then 6-monthly to 5 yrs (ii) Quantitative CMV PCR at Day -2 (baseline), + 48 hrs, +7d, +14d, then weekly until +6 wks, bi-weekly until + 12 weeks, then +4m, +5m, +6m, +8m, +10m,+12m, then 6-monthly to 5 yrs (iii) GVHD assessments at Day -2, +6hrs, 7d, then weekly until +6 weeks, bi-weekly until + 12 wks, then +4m, +5m, +6m, +8m, +10m,+12m, then 6-monthly to 5 yrs (iv) T cell reconstitution: Day -2 (baseline), +7d, +14d, +28d, +6w, +10w, +4m, +5m, +6m, +8m, +10m, +12m, then 6-monthly to 5 yrs (v) Persistence: Time 0, +6hrs, +24hrs, +48hrs, +72hrs, 7d, then weekly until +6 wks, bi-weekly until + 12 wks, then +4m, +5m, +6m, +8m, +10m, +12m, then 6-monthly to 5 yrs

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Countries

United Kingdom

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026