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)
18 Years
65 Years
Both
Acute Lymphoblastic Leukemia, Acute Myelogenous Leukemia, Lymphoma
Trial Information
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 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.
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.
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
BPX-501 dose that produces no more than 45% Grade II-IV aGVHD and no more than 17% Grade III-IV aGvHD
Outcome Description:
To determine the maximum dose of BPX-501 cells (up to 5 x 10E6 cells/kg) which results in an adjusted cumulative incidence by day 100 of no more than 45% Grade II-IV aGVHD and nor more than 17% Grade III-IV aGvHD. Adjusted cumulative incidence is the total aGvHD cumulative incidence minus the AP1903 GvHD response.
Outcome Time Frame:
100 days
Safety Issue:
Yes
Principal Investigator
Hillard Lazarus, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
University Hospitals of Cleveland
Authority:
United States: Food and Drug Administration
Study ID:
BP-HM-001
NCT ID:
NCT01744223
Start Date:
March 2013
Completion Date:
July 2016
Related Keywords:
- Acute Lymphoblastic Leukemia
- Acute Myelogenous Leukemia
- Lymphoma
- iCaspase9
- iCasp9
- Inducible Caspase
- AP1903
- Dimerizer drug
- T depleted
- Suicide gene
- CD-34 selection
- haplotransplantation
- Graft versus host disease
- Allogenic transplantation
- Leukemia
- Leukemia, Lymphoid
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Leukemia, Myeloid, Acute
- Leukemia, Myeloid
- Lymphoma
Name | Location |
|---|---|
| University Hospitals of Cleveland | Cleveland, Ohio 44106 |
| Baylor Charles A Sammons Cancer Center | Dallas, Texas 75246 |
