Safety Study of Gene Modified Donor T-cells Following Partially Mismatched Stem Cell Transplant
Verified April 2016 by Bellicum Pharmaceuticals
Information provided by (Responsible Party):
First received: December 5, 2012
Last updated: May 24, 2016
Last verified: April 2016
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.
Acute Lymphoblastic Leukemia
Acute Myelogenous Leukemia
Biological: BPX-501 and AP1903
||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||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)
Primary Outcome Measures:
Secondary Outcome Measures:
| Estimated Enrollment:
| Study Start Date:
| Estimated Study Completion Date:
| Estimated Primary Completion Date:
||January 2017 (Final data collection date for primary outcome measure)
Experimental: BPX-501 and AP1903
BPX-501 and AP1903
Biological: BPX-501 and AP1903
Patients will receive BPX-501 Donor T cells genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene after the stem cell graft infusion is complete, but not more than 72 hours after completion of the stem cell allograft infusion.
AP1903: Dimerizer drug administered (per intravenous infusion ) 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.
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.
|Ages Eligible for Study:
||18 Years to 65 Years (Adult)
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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%.
- 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.
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01744223
|Roswell Park Cancer Institute
|Buffalo, New York, United States, 14263 |
|Contact: Angela Kader 716-845-4485 email@example.com |
|Principal Investigator: George Chen, M.D. |
|Oregon Health & Science University
|Portland, Oregon, United States, 97239 |
|Contact: Chelsea Kline, BA, CCRP 503-418-0128 firstname.lastname@example.org |
|Principal Investigator: Richard T. Maziarz, M.D. |
|UT Southwestern Medical Center
|Dallas, Texas, United States, 75390 |
|Contact: Ryan Woelfel, CRC 214-648-5130 email@example.com |
|Principal Investigator: Madhuri Vusirikala, M.D. |
|Fred Hutchinson Cancer Research Center
|Seattle, Washington, United States, 98109 |
|Contact: Michele Bouvier 206-667-6993 firstname.lastname@example.org |
|Principal Investigator: Brenda M Sandmaier, MD |
||Hillard Lazarus, M.D.
||University Hospital Case Medical Center
History of Changes
|Other Study ID Numbers:
|Study First Received:
||December 5, 2012
||May 24, 2016
||United States: Food and Drug Administration
|Individual Participant Data
|Plan to Share IPD:
Keywords provided by Bellicum Pharmaceuticals:
Graft versus host disease
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on July 21, 2016
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Immune System Diseases