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