Safety Study of Gene Modified Donor T-cells Following Partially Mismatched Stem Cell Transplant

Study ID
STU 042013-067

Study Sites

  • Clements University Hospital

Contact
James Pond
214/648-7030
BLAKE.POND@UTSouthwestern.edu

Principal Investigator
Madhuri Vusirikala

Official Title

A Phase 1/2 Dose Escalation Study Evaluating Safety and Feasibility of BPX-501 T Cells After Partially Mismatched, Related, T Cell-Depleted HSCT (Hematopoietic Stem Cell Transplant)

Brief Overview

This study will evaluate patients with blood cell cancers who are going to have an allogeneic (donor) blood stem cell transplant from a partially matched relative. The research study will test whether immune cells, called T cells, which come from the donor relative and are specially grown in the laboratory and then given back to the patient along with the stem cell transplant (T cell addback), can help the immune system recover faster after the transplant. As a safety measure, these T cells have been "programmed" with a "self-destruct switch" so that if, after they have been given to the patient, the T cells start to react against the tissues (called "graft versus host" disease, GVHD), the T cells can be destroyed.

Description

This is a Phase1/2 dose escalation study evaluating the safety and feasibility of BPX-501 infused after partially mismatched, related (haploidentical), T cell-depleted HSCT. The purpose of this clinical trial is to determine whether BPX-501 infusion can facilitate engraftment, enhance immune reconstitution and potentially improve the graft versus leukemia (GVL) effect, with the potential for reducing the severity and duration of severe acute graft versus host disease (GvHD). The trial will evaluate the treatment of GvHD by the infusion of dimerizer drug (AP1903) in those subjects who present with severe GvHD (Grades III and IV) as well as those subjects with Grade I and II who progress or do not respond to corticosteroid therapy within 4 days.

Eligibility

Inclusion Criteria:
- Lack of suitable conventional donor (i.e. 7/8 or 8/8 related or 7/8 or 8/8 unrelated donor) or presence of rapidly progressive disease not permitting time to identify an unrelated donor
- HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, and DRBl, and loci. A minimum match of 5/10 is required. The donor and recipient must be identical, as determined by high resolution typing, at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, and HLA- DRB1.
- Subjects with adequate physical function as measured by:a)Cardiac: Left ventricular ejection fraction at rest must be >35%, or shortening fraction > 25%. b)Hepatic: Bilirubin < 2.5 mg/dL; and ALT, AST, and Alkaline Phosphatase < 5 x ULN. c)Renal: Serum creatinine within normal range for age, or creatinine clearance or GFR > 40 mL/min/1.73m2. d)Pulmonary: FEV 1, FVC, DLCO (diffusion capacity) > 50% predicted (corrected for hemoglobin); or 02 saturation > 92% on room air.
- Clinical Diagnosis of one of the following: Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia, Lymphoma
- Subjects must have received cytotoxic chemotherapy within 3 months of consent date (measured from the start date of chemotherapy).
- Performance status: Karnofsky/Lansky score > 60%.
Exclusion Criteria:
- HLA-matched, related or 7-or 8/8 allele matched (HLA-A,-B,-Cw,-DRBl) unrelated donor able to donate.
- Autologous hematopoietic stem cell transplant < 3 months prior to enrollment.
- Pregnancy or breast-feeding.
- Evidence of HIV infection or known HIV positive serology.
- Current uncontrolled bacterial, viral or fungal infection (currently taking medication with evidence of progression of clinical symptoms or radiologic findings).
- Non-hematologic malignancy within prior three (3) years.
- Prior allogeneic hematopoietic stem cell transplant.
- Subjects with a history of primary idiopathic myelofibrosis.
- Bovine product allergy.