Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation — ILD-TK01  

Hematological Malignancy Clinical Trial

Official title: Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation: a Phase I/II Clinical Study

Status Completed

Clinical Trial Summary

The main complications of allogeneic hematopoietic stem cell transplantation (HSCT) include graft-versus-host disease (GVHD) and poor immune reconstitution leading to severe infections and leukemia relapse. Mature donor T-cells present in the transplant facilitate T-cell reconstitution but also induce GVHD, which itself impairs immune reconstitution. We have developed a strategy of alloreactive T-cell depletion, using T-cells expressing the Herpes simplex thymidine kinase (TK) suicide gene combined with a ganciclovir (GCV) treatment. This system permits the selective elimination of dividing TK+ T-cells in vivo. To test this hypothesis in preclinical settings, we have previously developed several experimental models of GVHD using TK+ T-cells in mice. The demonstration that a preventive treatment with GCV administered close to the time of HSCT could control GVHD brought the proof of concept. We now propose a clinical trial to test whether donor lymphocytes infusion (DLI) using TK-transduced cells permits to induce a graft-versus-tumor (GVT) effect for treatment of relapse after HSCT, while GVHD can be controlled by GCV treatment.

Clinical Trial Description

DLI-TK is administered either after failure of 1 or several previous standard (std-) DLI of, defined after a minimal follow-up of 2 months after the last injection. To prepare DLI-TK, donor T-cells are transduced with a retroviral vector encoding TK. Transduced cells are selected using a CliniMACS device (MYLTENYI). In case of previous std-DLI received, the DLI-TK cell dose is adjusted to be below or equal to the maximal cell dose previously received in std-DLI. No comparison is planned in the analysis. ;

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hematological Malignancy

• NCT number: NCT01086735
• Study type: Interventional
• Source: Assistance Publique - Hôpitaux de Paris
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 2010
• Completion date: November 2012