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

AGC Biologics

Status and phase

Completed

Phase 2

Phase 1

Conditions

Hematological Malignancies

Treatments

Genetic: HSV-TK

Study type

Interventional

Funder types

Industry

Identifiers

NCT00423124

TK007

2005-003587-34 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

57 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients >=18 years old affected by hematological malignancies at high risk of relapse based on disease progression or presence of negative prognostic factors, who have received a HCT from donor HLA mismatched (haploidentical) for 2 or 3 loci
Engraftment documented by >500 neutrophils/µl for three consecutive days in the absence of growth factors
Mixed chimerism or full donor chimerism confirmed
AML in 1st or 2nd relapse or primary refractory
High-risk AML in 1st or subsequent remission
RAEB and RAEB-T
CML in 2nd chronic phase, blast crisis or accelerated phase
Poor prognosis ALL in 1st or subsequent remission
High grade lymphomas in 3rd or subsequent remission
Multiple myeloma in advanced stage relapsing or progressing after high dose chemotherapy
Absence of fully HLA matched or one HLA locus mismatched family donor
Stable clinical conditions and life expectancy >3 months
PS Karnofsky >70
Written donor/patient informed consent

Exclusion criteria

Infection with cytomegalovirus being treated with ganciclovir
Presence of GvHD grade > I that requires systemic immunosuppressive therapy (at baseline)
Ongoing systemic immunosuppressive therapy
Ongoing acyclovir administration
Administration after haplo-HCT of G-CSF and cyclosporine A
CD3+ lymphocytes >100/µl before day +42 after haplo-HCT
Life-threatening condition or complication other than their basic disease
CNS disease
Pregnant or lactating women