Safety Study of Gene Modified Donor T-cells Following TCR Alpha Beta Depleted Stem Cell Transplant

Study ID
STU 072014-023

Study Sites

  • Children’s Medical Center (Dallas, Plano, Southlake)

Contact
Colton Castle
2144562613
colton.castle@childrens.com

Principal Investigator
Victor Aquino, M.D.

Official Title

Phase I/II Study of CaspaCIDe T Cells From an HLA-partially Matched Family Donor After Negative Selection of TCR Alpha Beta T Cells in Pediatric Patients Affected by Hematological Disorders

Brief Overview

This study will evaluate pediatric patients with malignant or non-malignant blood cell disorders who are having a blood stem cell transplant depleted of T cell receptor (TCR) alfa and beta cells that comes from a partially matched family donor. The study will assess whether immune cells, called T cells, from the family donor, that are specially grown in the laboratory and given back to the patient along with the stem cell transplant can help the immune system recover faster after transplant. As a safety measure these T cells have been programmed with a self-destruct switch so that they can be destroyed if they start to react against tissues (Graft versus host disease).

Description

This is a Phase 1/2 study evaluating the safety and feasibility of BPX-501 T cells infused after partially mismatched, related, TCR alpha beta T cell depleted hematopoietic stem cell transplant (HSCT) in pediatric patients. The purpose of this clinical trial is to determine whether BPX-501 infusion can enhance immune reconstitution and retain the graft versus leukemia (GVL) effect, with the potential for reducing the severity and duration of severe acute GvHD. The trial will evaluate the treatment of GvHD by the infusion of dimerizer drug (AP1903/rimiducid) in those subjects who present with Grade III-IV acute GVHD, as well as those subjects with Grade II gut/liver GvHD or with Grade I/II GvHD (skin only) who progress or do not respond within 7 days to standard of care treatment.

Eligibility

Inclusion Criteria:
- Children with life-threatening hematological malignancies, deemed eligible for allogeneic stem cell transplantation
- Children with non-malignant disorders amenable to be cured by an allograft
- Lack of HLA identical donor
- Life expectancy > 10 weeks
- Lansky/Karnofsky score > 50
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 (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance < 30 ml / min)
- Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction <40%)
- Current active infectious disease (including positive HIV serology or viral RNA)
- Serious concurrent uncontrolled medical disorder
- Pregnant or breast feeding female patient