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Completed

NCT Number: NCT01086735

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

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.

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Key information

Conditions

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

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Groupe Hospitalier Albert Chenevier-Henri Mondor

Créteil, 94, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

donor lymphocyte infusion

Biological

Donor T-cell transduction

Primary outcomes

  1. 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

Secondary outcomes

  1. 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

  2. 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

  3. 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

Sponsors and collaborators

Lead sponsor

Assistance Publique - Hôpitaux de Paris

Other

Collaborators

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

Registry information

Official study title

Suicide Gene Therapy for Donor Lymphocytes Infusion After Allogeneic Hematopoietic Stem Cell Transplantation: a Phase I/II Clinical Study

Acronym: ILD-TK01

Important dates

Study start
2010
Primary completion
2012
Study completion
2012
First posted
Mar 15, 2010
Registry last updated
Jan 14, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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