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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 August 28, 2014