NCT00423124

Infusion of Donor Lymphocytes Transduced With the Suicide Gene HSV TK in Patients With Haematological Malignancies

A Phase I-II Study: Infusion of Donor Lymphocytes Transduced With the Suicide Gene HSV TK, After Transplantation of Allogeneic T-depleted Stem Cells From a Haploidentical Donor in Patients With Haematological Malignancies

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 57 (actual)
• Sponsor: AGC Biologics S.p.A. · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The aim of the study is to obtain immune reconsitutuion as well as reduction of infective episodes and disease relapse in patient with haematological malignancies who underwent SCT(and subsequent T lymphocytes infusions) and selectively controlling GvHD.

Detailed description

Delayed immune-reconstitution remains one of the main limitation of haploidentical stem cell transplantation. The risk of severe infections remains high for several months and CD4+ reconstitution could take more than 10 months. The low number of lymphocytes infused with the graft, the degree of HLA disparity, and a reduced thymic function in adults and differences in host/donor antigen presenting cells are contributing causes. The infusions of HSV-TK engineered lymphocytes may represent a significant therapeutic improvement in haploidentical haplo-HCT, because it remarkably may enhance both GvL activity, thus reducing the occurrence of disease relapse, and post-transplant immune reconstitution in the absence of chronic immune suppression, thus decreasing the rate of both post-transplant opportunistic infections and transplant-related mortality. Furthermore, the efficient control of GvHD achieved via the suicide mechanism allows also the multiple infusion of HSV-TK-treated donor lymphocytes, when needed, that might further improve post-transplant host immune reconstitution, and, eventually, survival in patients receiving haplo-HCT. Finally, this therapeutic approach, which allows the safe infusion of escalating doses of donor lymphocytes, can become a valuable option for all candidates, including patients with advanced disease and older age. The proposed clinical trial represents an innovative therapeutic treatment for patients affected by hematological malignancies, who have undergone haploidentical stem cell transplantation.

Conditions

• Hematological Malignancies

Interventions

Type	Name	Description
GENETIC	HSV-TK	Infusion of genetically modified lymphocytes (1x10\^6-1x10\^7 c/kg): first at +21-+49 days after HSCT; in absence of immune reconstitution and GvHD further infusions up to 4 will be administered on monthly basis.

Timeline

• Start date: 2002-07-01
• Primary completion: 2011-12-01
• Completion: 2013-11-01
• First posted: 2007-01-17
• Last updated: 2014-05-30

Locations

8 sites across 5 countries: Germany, Greece, Israel, Italy, United Kingdom