- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03301168
Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
Phase I/II Study of CaspaCIDe® T Cells From an HLA-Partially Matched Family Donor After Negative Selection of TCR αβ+T Cells in Pediatric Patients Affected by Hematological Disorders
Study Overview
Status
Conditions
Intervention / Treatment
Detailed 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.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Expanded Access
Contacts and Locations
Study Locations
-
-
California
-
Los Angeles, California, United States, 90027
- Children's Hospital Los Angeles
-
Palo Alto, California, United States, 94304
- Stanford University - Division of Pediatric Stem Cell Transplant & Regenerative Medicine
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-
District of Columbia
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Washington, District of Columbia, United States, 20010
- Children's National Medical Center
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-
Georgia
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Atlanta, Georgia, United States, 30322
- Children's Healthcare of Atlanta
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Massachusetts
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Boston, Massachusetts, United States, 02215
- Dana-Farber Boston Children's Cancer and Blood Disorders Center
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-
New York
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Bronx, New York, United States, 10467
- Children's Hospital at Montefiore
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Oregon
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Portland, Oregon, United States, 97239
- Oregon Health Sciences University - Doernbecher Children's Hospital
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Texas
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Dallas, Texas, United States, 77390
- University of Texas Southwestern-Children's Medical Center
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Houston, Texas, United States, 77030
- Baylor College of Medicine/ Texas Children's Hospital
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Washington
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Seattle, Washington, United States, 98109
- Fred Hutchinson Cancer Research Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age > 1 month and < 26 years
- Life expectancy > 10 weeks
- Subjects deemed eligible for allogeneic stem cell transplantation.
- 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);
Non-malignant disorders amenable to cure by an allograft:
- primary immune deficiencies,
- severe aplastic anemia not responding to immune suppressive therapy,
- osteopetrosis,
- hemoglobinopathies, (thalassemias, and sickle cell anemia, and Diamond-Blackfan anemia among others)
- 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.
- 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
- A minimum genotypic identical 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, HLA- DRB1 and HLA-DQB1.
- Lansky/Karnofsky score > 50
- Signed written informed consent
Exclusion Criteria:
- Greater than Grade II acute GVHD or chronic extensive GVHD due to a previous allograft at the time of inclusion
- Subject receiving an immunosuppressive treatment for GVHD treatment due to a previous allograft at the time of inclusion
- Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance < 30 mL / min)
- Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction < 40%)
- Current active infectious disease (including positive HIV serology or viral RNA)
- Serious concurrent uncontrolled medical disorder
- Pregnant or breastfeeding subject
- 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 Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: BPX-501 T cells and Rimiducid
TCR alpha beta depleted graft infusion with addback of BPX-501 T cells. Rimiducid: Dimerizer drug administered to subjects who present with Grade I-IV acute GVHD with inadequate response to steroids within 48 hours of treatment or mild to severe chronic GVHD with inadequate response to steroids within 7 days of treatment. |
T cells transduced with CaspaCIDe® safety switch
Other Names:
administered to inactivate BPX-501 cells in the event of GVHD
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse Event
Time Frame: Month 24
|
Demonstrate safety of BPX-501 MTD
|
Month 24
|
TRM/NRM
Time Frame: Day 180, Month 12
|
Assess the cumulative incidence of non-relapse/transplant related mortality
|
Day 180, Month 12
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Disease-free survival
Time Frame: Month 24
|
Disease-free survival rates after transplantation
|
Month 24
|
Relapse
Time Frame: Month 12
|
Cumulative incidence of relapse
|
Month 12
|
Engraftment
Time Frame: Month 24
|
Cumulative incidence of neutrophil and platelet engraftment, primary & secondary graft failure
|
Month 24
|
GvHD
Time Frame: Month 24
|
Cumulative incidence and severity of acute and chronic GvHD
|
Month 24
|
Rimiducid Efficacy
Time Frame: Month 24
|
Time to resolution of acute or chronic GvHD after administration of rimiducid
|
Month 24
|
Infection
Time Frame: Month 24
|
Rate of infectious complications
|
Month 24
|
Hospitalizations
Time Frame: Month 24
|
Duration of hospitalization and rehospitalization
|
Month 24
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ANTICIPATED)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Bone Marrow Diseases
- Hematologic Diseases
- Genetic Diseases, Inborn
- Musculoskeletal Diseases
- Anemia
- Bone Diseases
- Leukemia, Lymphoid
- Bone Marrow Failure Disorders
- Lymphoma
- Bone Diseases, Developmental
- Osteochondrodysplasias
- Leukemia, Myeloid
- Osteosclerosis
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid, Acute
- Lymphoma, Non-Hodgkin
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Immunologic Deficiency Syndromes
- Primary Immunodeficiency Diseases
- Anemia, Aplastic
- Hemoglobinopathies
- Osteopetrosis
Other Study ID Numbers
- BP-U-004
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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