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

Primary Purpose

Hematological Malignancy

Status

Completed

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

donor lymphocyte infusion

About this trial

This is an interventional treatment trial for Hematological Malignancy focused on measuring hematological malignancy, allogeneic hematopoietic stem cell transplantation, donor lymphocyte infusion, antitumor immunotherapy, graft-versus-tumor effect, gene therapy, relapse, adult

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

Groupe Hospitalier Albert Chenevier-Henri Mondor

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

donor lymphocyte infusion

Arm Description

Donor T-cell transduction

Outcomes

Primary Outcome Measures

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

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

Full Information

NCT ID

NCT01086735

First Posted

March 12, 2010

Last Updated

January 11, 2013

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT01086735

Brief Title

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

Acronym

ILD-TK01

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2013

Overall Recruitment Status

Completed

Study Start Date

February 2010 (undefined)

Primary Completion Date

November 2012 (Actual)

Study Completion Date

November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

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

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematological Malignancy

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

11 (Actual)

8. Arms, Groups, and Interventions

Arm Title

donor lymphocyte infusion

Arm Type

Experimental

Arm Description

Donor T-cell transduction

Intervention Type

Biological

Intervention Name(s)

donor lymphocyte infusion

Intervention Description

Donor T-cell transduction

Primary Outcome Measure Information:

Title

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

Description

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

Secondary Outcome Measure Information:

Title

The incidence of GVHD of any grade after DLI-TK

Description

The incidence of GVHD of any grade after DLI-TK

Time Frame

during the 12 months of follow-up

Title

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

Description

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

Time Frame

during the 12 months of follow-up

Title

The survival and the survival without disease after DLI-TK

Description

The survival and the survival without disease after DLI-TK

Time Frame

during the 12 months of follow-up

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

70 Years

Accepts Healthy Volunteers

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sébastien Maury, MD, PhD

Organizational Affiliation

Assistance Publique - Hôpitaux de Paris

Official's Role

Principal Investigator

Facility Information:

Facility Name

Groupe Hospitalier Albert Chenevier-Henri Mondor

City

Creteil

ZIP/Postal Code

Country

France

12. IPD Sharing Statement

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

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