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 (Rimiducid) in those subjects who present with GvHD that does not adequately respond to standard of care therapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
36
Subjects will receive 2x10E5 donor T cells/kg genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene (BPX-501) after stem cell transplant.
Dimerizer drug administered by intravenous infusion in those subjects who develop GVHD after infusion of BPX-501 cells.
Subjects will receive 5x10E5 donor T cells/kg genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene (BPX-501) after stem cell transplant.
Subjects will receive 1x10E6 donor T cells/kg genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene (BPX-501) after stem cell transplant.
Subjects will receive 3x10E6 donor T cells/kg genetically modified with BPZ-1001 retroviral vector containing the iCasp suicide gene (BPX-501) after stem cell transplant.
all subjects will receive an alpha beta depleted donor transplant as part of treatment
Emory University Winship Cancer Institute
Atlanta, Georgia, United States
Roswell Park Cancer Institute
Buffalo, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
University Hospitals of Cleveland
Cleveland, Ohio, United States
Oregon Health & Science University
Portland, Oregon, United States
Baylor Sammons Cancer Center
Dallas, Texas, United States
UT Southwestern Medical Center
Dallas, Texas, United States
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
BPX-501 Safety
To evaluate the safety of infusion of each of 4 dose cohorts of BPX-501 (2x105, 5x105, 1x106 and 3x106 cells/kg) after transplantation of partially mismatched T cell depleted hematopoietic stem cell transplant (HSCT)
Time frame: 24 months
Rimiducid Safety
To evaluate the safety of the infusion of the rimiducid in subjects who received BPX-501 and have developed visceral or steroid refractory graft-versus-host-disease
Time frame: 24 months
MTD
To determine the maximum dose of BPX-501 (up to 3x106 cells/kg) that results in an adjusted cumulative incidence by Day 100 of no more than 45% Grade II - IV aGVHD and / or no more than 17% Grade III -IV aGVHD.
Time frame: 24 months
Immune Reconstitution
To assess immune reconstitution for each dose cohort
Time frame: 24 months
Efficacy- NRM
Non-Relapse Mortality (NRM)
Time frame: 100, 180 days and 1 year
Efficacy- DFS
Disease-free survival
Time frame: 24 months
Efficacy- TRM
Transplant related mortality (TRM)
Time frame: 24 months
Efficacy- Relapse
Incidence of Relapse
Time frame: 24 months
Incidence of engraftment
Evaluation of neutrophil and platelet engraftment, kinetics of donor cell engraftment and graft failure
Time frame: 24 months
GvHD
Incidence and severity of acute and chronic GvHD
Time frame: 24 months
GvHD post Rimiducid Administration
Time to resolution of acute GvHD after administration of Rimiducid
Time frame: 24 months
BPX-501 Safety Profile
Characterize the safety profile of BPX-501 including evaluation of high grade toxicity and infectious complications
Time frame: 24 months
Pharmacokinetics of Rimiducid
Pharmacokinetic disposition of Rimiducid
Time frame: 24 months
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