Trial | NCT01086735  Report issue

Title

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

  • Phase

    Phase 1/Phase 2

  • Study Type

    Interventional

  • Status

    Completed No Results Posted

  • Study Participants

    11
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.
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 Started
Feb 28
2010
Primary Completion
Nov 30
2012
Study Completion
Nov 30
2012
Last Update
Jan 14
2013
Estimate

Biological donor lymphocyte infusion

Donor T-cell transduction

donor lymphocyte infusion Experimental

Donor T-cell transduction

Criteria 

Inclusion Criteria:

Hematological malignancy.
Previous allogeneic hematopoietic stem cell transplantation.
Relapse diagnosed at the molecular, cytogenetic, or cytological level.
Failure of a previous stdILD or inclusion in first intention without previous stdDLI.
Age > 18 years and < 70 years at the time of inclusion. For patients between 15 and 18 years of age, a case-per case inclusion will be studied.
Performance status considered on the score Eastern Cooperative Oncology Group (ECOG) < 2.
Life expectation 1-month-old superior.
Signed written informed consent.
Negative human chorionic gonadotropin (HCG) in the 7 days preceding the inclusion for women in age of procreation.
Membership of the French national insurance.

Exclusion Criteria:

Grade >II acute GVHD or chronic extensive GVHD at the time of inclusion.
Patient receiving an immunosuppressive treatment for GVHD treatment at the time of inclusion.
Dysfunction of liver (alanine aminotransferase / aspartate transaminase (ALAT/ASAT) > 5 N, or bilirubin > 50 µM), or of the renal function (creatinine clearance < 30 ml / min).
No Results Posted