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

• ClinicalTrials.gov Identifier: NCT01086735
• Recruitment Status: Completed
• First Posted: March 15, 2010
• Last Update Posted: January 14, 2013
• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Paris 12 Val de Marne University; Pierre and Marie Curie University
• Information provided by (Responsible Party): Assistance Publique - Hôpitaux de Paris

Tracking Information

• First Submitted Date: March 12, 2010
• First Posted Date: March 15, 2010
• Last Update Posted Date: January 14, 2013
• Study Start Date: February 2010
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 12, 2010)

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 ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 12, 2010)

• The incidence of GVHD of any grade after DLI-TK [ Time Frame: during the 12 months of follow-up ]
  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 ]
  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 ]
  The survival and the survival without disease after DLI-TK

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation
• Official Title: Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation: a Phase I/II Clinical Study
• 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.
• 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.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hematological Malignancy

Intervention

Biological: donor lymphocyte infusion

Donor T-cell transduction

Study Arms

Experimental: donor lymphocyte infusion

Donor T-cell transduction

Intervention: Biological: donor lymphocyte infusion

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: November 19, 2012): 11
• Original Estimated Enrollment (submitted: March 12, 2010): 12
• Actual Study Completion Date: November 2012
• Actual Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)

Eligibility 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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France

Administrative Information

• NCT Number: NCT01086735
• Other Study ID Numbers: P010506
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Assistance Publique - Hôpitaux de Paris
• Study Sponsor: Assistance Publique - Hôpitaux de Paris

Collaborators

• Paris 12 Val de Marne University
• Pierre and Marie Curie University

Investigators

• Principal Investigator: Sébastien Maury, MD, PhD; Assistance Publique - Hôpitaux de Paris

• PRS Account: Assistance Publique - Hôpitaux de Paris
• Verification Date: January 2013