Primary Objective• To investigate the feasibility and safety of administration of donor HA-1 TCR transduced virus-specific T-cells after allo-SCT.Secondary Objectives• To evaluate the persistence of donor HA-1 TCR transduced virus-specific T-cells…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• The number of events of acute GvHD, all other adverse events and death.
• The feasibility of generation of HA-1 TCR transduced virus-specific donor
T-cells.
Secondary outcome
• The number of HA-1 TCR transduced virus-specific donor T-cells in blood or
bone marrow at different time points.
• The number of patients eligible for standard DLI at 6 months.
Background summary
Patients with hematological malignancies can be successfully treated with
allogeneic stem cell transplantation (allo-SCT). In T-cell depleted allo-SCT
administration of donor T-cells via a donor lymphocyte infusion (DLI) can
induce graft-versus-leukemia (GvL) which can cure relapse or refractory
hematological malignancies. However, infusion of DLI before 6 months has a high
risk of morbidity and mortality caused by graft-versus-host disease (GvHD) due
to alloreactive T-cells in the product. Patients with high-risk acute leukemia
are likely to relapse within 6 months after allo-SCT, when DLI is undesirable
due to the high risk of developing GvHD. Administration of leukemia specific
T-cells with minimal amount of alloreactive T-cells at 8 weeks after allo-SCT
might cause GvL without GVHD. Minor histocompatibility antigen (MiHA) HA-1 is
exclusively expressed on cells of the hematopoietic system and administration
of HA-1 T-cell receptor (TCR) transduced virus-specific T-cells at 8 and 14
weeks may exert selective GvL activity in allo-SCT patients with high-risk
acute leukemia.
Study objective
Primary Objective
• To investigate the feasibility and safety of administration of donor HA-1 TCR
transduced virus-specific T-cells after allo-SCT.
Secondary Objectives
• To evaluate the persistence of donor HA-1 TCR transduced virus-specific
T-cells after administration.
• To evaluate whether administration of donor HA-1 TCR transduced
virus-specific T-cells after allo-SCT makes patients eligible for standard DLI
at 6 months after allo-SCT.
Study design
This is an open-label non-randomized phase I/II feasibility study to treat
patients with high-risk leukemia with HA-1 TCR transduced virus-specific
donor-derived T-cells 8 and 14 weeks after allo-SCT.
Intervention
Administration of HA-1 TCR transduced virus-specific donor T-cells 8 weeks
after allo-SCT. This administration may be repeated 6 weeks later.
Study burden and risks
Potential benefits of administration of HA-1 TCR transduced virus-specific
donor T-cells is selective GvL activity and prevention of CMV-and/or EBV
reactivation. The risk for development of acute GvHD, neoreactivity, oncogenic
transformation and infection will be kept to a minimum by critical steps in the
manufacturing process.
Postbus 9600
2300 RC
NL
Postbus 9600
2300 RC
NL
Listed location countries
Age
Inclusion criteria
• Age 18-75 years
• WHO performance score 0-2
• High-risk leukemia (see appendix D)
• Complete remission (CR) or stable partial remission (PR) (see appendix D)
• HLA-A*0201 positive
• HA-1h positive
• Availability of a suitable donor (see donor criteria)
• Written informed consent
Exclusion criteria
• Life expectation < 3 months.
• End stage irreversible multi-system organ failure.
• Pregnant or lactating women.
• Severe psychological disturbances.
• HIV-positivity
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-024625-20-NL |
| CCMO | NL35240.000.12 |