T-allo10 Infusion Therapy to Prevent Graft Versus Host Disease and Improve Potential Immune Reconstitution in Patients who received Hematopoietic Stem Cell Transplantation

PRIMARY OBJECTIVES:

I. To determine the recommended phase 2 dose (RP2D) of escalating doses of T-allo10 infusions administered after B-cell depleted allogeneic hematopoietic stem cell transplantation (alpha beta depleted-HSCT). A single dose of T-allo10 will be infused 35 (+/- 7 days) days after alpha beta depleted-HSCT in the presence of myeloid engraftment and in the absence of signs of grade II acute graft-versus-host disease (aGvHD) requiring > 0.5 mg/Kg of steroids or grade III/IV aGvHD. (Phase 1)

II. To assess the safety of T-allo10 infusion at the RP2D administered after receipt of allogeneic hematopoietic stem cell transplantation (HSCT) under the alpha beta depleted-HSCT protocol (BMT 361). (Phase 1b)

III. To explore possible improvement in immune reconstitution defined as an increased proportion of patients who reach the threshold of 50 CD3+CD4+ T cells/Pl by Day +60 (+/- 10 days) in comparison to the controls. (Phase 1b)

SECONDARY OBJECTIVES:

I. To assess the long-term safety of the T-allo10 infusion after alpha beta depleted-HSCT defined as the occurrence of any severe (>= grade 3) adverse events attributable to T-allo10 infusion up to 1 year after alpha beta depleted-HSCT.

II. To assess the incidence of grade II-IV and grade III-IV aGvHD at Day +90 and Day +180 after alpha beta depleted-HSCT.

III. To assess the incidence and severity of chronic GvHD (cGvHD) at 1 year after alpha beta depleted-HSCT.

IV. To assess leukemia-free survival (LFS) at 1 year after alpha beta depleted-HSCT.

V. To assess the incidence of relapse at 1 year after alpha beta depleted-HSCT.

VI. To assess Non-Relapse Mortality (NRM) at Day +90 and 1 year after alpha beta depleted-HSCT.

EXPLORATORY OBJECTIVES:

I. To assess immune reconstitution (IR) of cell subsets other than CD3+CD4+ T cells in patients receiving alpha beta depleted-HSCT combined with T-allo10 infusion.

II. To assess mitogen and antigen-specific functional assay responses in patients receiving alpha beta depleted-HSCT combined with T-allo10 infusion.

III. To perform tracking of T-allo10 cells evaluated by T-cell receptor (TCR) sequencing after alpha beta depleted-HSCT.

IV. To assess event-free-survival (EFS) at 1 year after DEdepleted-HSCT.

V. To assess the incidence of secondary graft failure at 1 year after alpha beta depleted-HSCT in patients receiving T-allo10 infusion.

VI. To assess incidences of viral reactivations at Day +180 after DE depleted-HSCT in patients receiving T-allo10 infusion.

OUTLINE: This is a dose-escalation study.

Patients receive T-allo10 intravenously (IV) on day 35 post transplant.