Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation

NCT01086735 | Completed Phase 1

• 1 other identifier: P010506
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hematological Malignancy

Keywords

hematological malignancy; allogeneic hematopoietic stem cell transplantation; donor lymphocyte infusion; antitumor immunotherapy; graft-versus-tumor effect; gene therapy; relapse; adult

Outcome Measures

Primary Outcomes (1)

• Incidence of "severe" GHVD (acute grade >II or chronic extensive) following DLI-TK and treatment with GCV

  Incidence of "severe" GHVD (acute grade \>II or chronic extensive) following DLI-TK and treatment with GCV

  during the 12 months of follow-up

Secondary Outcomes (3)

• The incidence of GVHD of any grade after DLI-TK

  during the 12 months of follow-up

• The anti-tumoral efficiency of DLI-TK to treat the relapse of the hematological malignancy

  during the 12 months of follow-up

• The survival and the survival without disease after DLI-TK

  during the 12 months of follow-up

Study Arms (1)

donor lymphocyte infusion

EXPERIMENTAL

Donor T-cell transduction

Biological: donor lymphocyte infusion

Interventions

donor lymphocyte infusion BIOLOGICAL

Donor T-cell transduction

donor lymphocyte infusion

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hematological malignancy.
• Previous allogeneic hematopoietic stem cell transplantation.
• Relapse diagnosed at the molecular, cytogenetic, or cytological level.
• Performance status considered on the score Eastern Cooperative Oncology Group (ECOG) \< 2.
• Life expectation 1-month-old superior.
• Signed written informed consent.
• Membership of the French national insurance.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Paris 12 Val de Marne University: collaborator
• Pierre and Marie Curie University: collaborator

Study Sites (1)

Groupe Hospitalier Albert Chenevier-Henri Mondor

Créteil, 94, France

Location

MeSH Terms

Conditions

Hematologic Neoplasms; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sébastien Maury, MD, PhD

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2010
• First Posted: March 15, 2010
• Study Start: February 1, 2010
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: January 14, 2013

Record last verified: 2013-01

Locations

FR (1)