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

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ClinicalTrials.gov Identifier: NCT01086735
Recruitment Status : Completed
First Posted : March 15, 2010
Last Update Posted : January 14, 2013
Sponsor:
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  ICMJE March 12, 2010
First Posted Date  ICMJE March 15, 2010
Last Update Posted Date January 14, 2013
Study Start Date  ICMJE February 2010
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (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  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation
Official Title  ICMJE 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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hematological Malignancy
Intervention  ICMJE Biological: donor lymphocyte infusion
Donor T-cell transduction
Study Arms  ICMJE Experimental: donor lymphocyte infusion
Donor T-cell transduction
Intervention: Biological: donor lymphocyte infusion
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 19, 2012)
11
Original Estimated Enrollment  ICMJE
 (submitted: March 12, 2010)
12
Actual Study Completion Date  ICMJE November 2012
Actual Primary Completion Date November 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01086735
Other Study ID Numbers  ICMJE P010506
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Assistance Publique - Hôpitaux de Paris
Study Sponsor  ICMJE Assistance Publique - Hôpitaux de Paris
Collaborators  ICMJE
  • Paris 12 Val de Marne University
  • Pierre and Marie Curie University
Investigators  ICMJE
Principal Investigator: Sébastien Maury, MD, PhD Assistance Publique - Hôpitaux de Paris
PRS Account Assistance Publique - Hôpitaux de Paris
Verification Date January 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP