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

This study has been completed.
Sponsor:
Collaborators:
Paris 12 Val de Marne University
Université Paris VI
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01086735
First received: March 12, 2010
Last updated: January 11, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Hematological Malignancy
Biological: donor lymphocyte infusion
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation: a Phase I/II Clinical Study

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Incidence of "severe" GHVD (acute grade >II or chronic extensive) following DLI-TK and treatment with GCV [ Time Frame: during the 12 months of follow-up ] [ Designated as safety issue: Yes ]
    Incidence of "severe" GHVD (acute grade >II or chronic extensive) following DLI-TK and treatment with GCV


Secondary Outcome Measures:
  • The incidence of GVHD of any grade after DLI-TK [ Time Frame: during the 12 months of follow-up ] [ Designated as safety issue: No ]
    The incidence of GVHD of any grade after DLI-TK

  • The anti-tumoral efficiency of DLI-TK to treat the relapse of the hematological malignancy [ Time Frame: during the 12 months of follow-up ] [ Designated as safety issue: No ]
    The anti-tumoral efficiency of DLI-TK to treat the relapse of the hematological malignancy

  • The survival and the survival without disease after DLI-TK [ Time Frame: during the 12 months of follow-up ] [ Designated as safety issue: Yes ]
    The survival and the survival without disease after DLI-TK


Enrollment: 11
Study Start Date: February 2010
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: donor lymphocyte infusion
Donor T-cell transduction
Biological: donor lymphocyte infusion
Donor T-cell transduction
Other Name: donor lymphocyte infusion

Detailed 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.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01086735

Locations
France
Groupe Hospitalier Albert Chenevier-Henri Mondor
Creteil, France, 94
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Paris 12 Val de Marne University
Université Paris VI
Investigators
Principal Investigator: Sébastien Maury, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01086735     History of Changes
Other Study ID Numbers: P010506
Study First Received: March 12, 2010
Last Updated: January 11, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
hematological malignancy
allogeneic hematopoietic stem cell transplantation
donor lymphocyte infusion
antitumor immunotherapy
graft-versus-tumor effect
gene therapy
relapse
adult

Additional relevant MeSH terms:
Neoplasms
Suicide
Hematologic Neoplasms
Self-Injurious Behavior
Behavioral Symptoms
Neoplasms by Site
Hematologic Diseases

ClinicalTrials.gov processed this record on April 17, 2014