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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT03301168
Other study ID # BP-U-004
Secondary ID
Status Active, not recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date April 2014
Est. completion date May 2034

Study information

Verified date May 2022
Source Bellicum Pharmaceuticals
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This study will evaluate pediatric patients with malignant or non-malignant blood cell disorders who are having a blood stem cell transplant depleted of T cell receptor (TCR) alfa and beta cells that comes from a partially matched family donor. The study will assess whether immune cells, called T cells, from the family donor, that are specially grown in the laboratory and given back to the patient along with the stem cell transplant can help the immune system recover faster after transplant. As a safety measure these T cells have been programmed with a self-destruct switch so that they can be destroyed if they start to react against tissues (graft versus host disease).


Description:

This is a Phase 1/2 study evaluating the safety and feasibility of BPX-501 T cells infused after partially mismatched, related, TCR alpha beta T cell depleted hematopoietic stem cell transplant (HSCT) in pediatric patients. The purpose of this clinical trial is to determine whether BPX-501 infusion can enhance immune reconstitution in those patients with hematologic disorders, with the potential for reducing the severity and duration severe acute graft versus host disease (GvHD). The trial will also evaluate the treatment of GvHD by the infusion of dimerizer drug (AP1903/rimiducid) in those subjects who present with GVHD that does not adequately respond to standard of care therapy.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 120
Est. completion date May 2034
Est. primary completion date May 11, 2021
Accepts healthy volunteers No
Gender All
Age group 1 Month to 26 Years
Eligibility Inclusion Criteria: 1. Age > 1 month and < 26 years 2. Life expectancy > 10 weeks 3. Subjects deemed eligible for allogeneic stem cell transplantation. 4. Subjects with life-threatening hematological malignancies (high-risk ALL in 1st CR, ALL in 2nd or subsequent CR, AML in 1st CR, AML in 2nd or subsequent CR, myelodysplastic syndromes, non-Hodgkin lymphomas in 2nd or subsequent CR, other hematologic malignancies eligible for stem cell transplantation per institutional standard); 5. Non-malignant disorders amenable to cure by an allograft: 1. primary immune deficiencies, 2. severe aplastic anemia not responding to immune suppressive therapy, 3. osteopetrosis, 4. hemoglobinopathies, (thalassemias, and sickle cell anemia, and Diamond-Blackfan anemia among others) 5. congenital/hereditary cytopenia, including Fanconi Anemia before any clonal malignant evolution (MDS, AML) Note: Subjects will be eligible if they meet either item 4 OR item 5. 6. Lack of suitable conventional donor (HLA identical sibling or HLA phenotypically identical relative or 10/10 unrelated donor evaluated using high resolution molecular typing) or presence of rapidly progressive disease not permitting time to identify an unrelated donor 7. A minimum genotypic identical match of 5/ 10 is required. 8. 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, HLA- DRB1 and HLA-DQB1. 9. Lansky/Karnofsky score > 50 10. Signed written informed consent Exclusion Criteria: 1. Greater than Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at the time of inclusion 2. Subject receiving an immunosuppressive treatment for GVHD treatment due to a previous allograft at the time of inclusion 3. Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance < 30 mL / min) 4. Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction < 40%) 5. Current active infectious disease (including positive HIV serology or viral RNA) 6. Serious concurrent uncontrolled medical disorder 7. Pregnant or breastfeeding subject 8. For subjects who have received more than 1 x 10E5 alpha/beta T cells/kg with the graft infusion the clinical trial site must contact the sponsor for approval to be eligible to receive BPX-501 infusion.

Study Design


Related Conditions & MeSH terms


Intervention

Biological:
BPX-501 T cells
T cells transduced with CaspaCIDe® safety switch
Drug:
Rimiducid
administered to inactivate BPX-501 cells in the event of GVHD

Locations

Country Name City State
United States Children's Healthcare of Atlanta Atlanta Georgia
United States Dana-Farber Boston Children's Cancer and Blood Disorders Center Boston Massachusetts
United States Children's Hospital at Montefiore Bronx New York
United States University of Texas Southwestern-Children's Medical Center Dallas Texas
United States Baylor College of Medicine/ Texas Children's Hospital Houston Texas
United States Children's Hospital Los Angeles Los Angeles California
United States Stanford University - Division of Pediatric Stem Cell Transplant & Regenerative Medicine Palo Alto California
United States Oregon Health Sciences University - Doernbecher Children's Hospital Portland Oregon
United States Fred Hutchinson Cancer Research Center Seattle Washington
United States Children's National Medical Center Washington District of Columbia

Sponsors (1)

Lead Sponsor Collaborator
Bellicum Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Adverse Event Demonstrate safety of BPX-501 MTD Month 24
Primary TRM/NRM Assess the cumulative incidence of non-relapse/transplant related mortality Day 180, Month 12
Secondary Disease-free survival Disease-free survival rates after transplantation Month 24
Secondary Relapse Cumulative incidence of relapse Month 12
Secondary Engraftment Cumulative incidence of neutrophil and platelet engraftment, primary & secondary graft failure Month 24
Secondary GvHD Cumulative incidence and severity of acute and chronic GvHD Month 24
Secondary Rimiducid Efficacy Time to resolution of acute or chronic GvHD after administration of rimiducid Month 24
Secondary Infection Rate of infectious complications Month 24
Secondary Hospitalizations Duration of hospitalization and rehospitalization Month 24
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