Adoptive Immunotherapy with CD25/71 allodepleted donor T cells to improve immunity after unrelated donor stem cell transplant.
Description
Design:
ICAT is a multi-centre randomised phase II trial in adult patients with an underlying haematological malignancy undergoing unrelated donor peripheral blood stem cell transplant with Alemtuzumab-based conditioning. Patients will be randomly allocated 2:1 in favour of those receiving the ATIMP (CD25/71 allodepleted donor T-cells) compared with an internal control group receiving standard of care therapy.
Treatment:
Patients on the ATIMP arm will undergo an unstimulated leucapheresis for generation of mature denditric cells two weeks prior to their SCT. The SCT donor will either undergo unstimulated leucapheresis or a 500ml whole blood draw for the generation of peripheral blood stem cells. The isolated donor peripheral blood stem cells will then be co-cultured with the irradiated recipient mature denditric cells and allodepletion performed using immunomagnetic CD25/71 negative selection using the CliniMACs system.
The allodepleted donor T cells will be infused intravenously at increasing doses (105 /kg at day 30 post-SCT [+/- 10 days], 3 x 105 /kg at day 60 [+/- 10 days] and 106 /kg at day 90 [+/- 10 days]) at monthly intervals post-SCT until either their circulating CD3 count is normal (>700/µL) or they develop acute GVHD > Grade I. Those in the control arm will receive identical supportive care, but will not receive the ATIMP.
Key inclusion/exclusion criteria:
Inclusion:
Underlying haematological malignancy
Planned allogeneic peripheral blood stem cell transplantation from a 9/10 or 10/10 human leukocyte antigen (HLA) matched unrelated donor, using an Alemtuzumab-based conditioning protocol
Absence of acute GVHD > Grade I
Exclusion:
Patients who are serologically positive for Hepatitis B, C or HIV pre-SCT
Duration of recruitment:
3 years
Aim
To determine whether adoptive immunotherapy with CD25/71 allodepleted donor T-cells can be safely used to improve T-cell reconstitution after unrelated donor stem cell transplant (SCT)