Back to resultsStudy of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
Primary Purpose
Acute Lymphoblastic Leukemia, Leukemia, Acute Myeloid (AML), Child, Lymphoma, Non-Hodgkin
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
BPX-501 T cells
Rimiducid
Sponsored by
About this trial
This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring ALL, AML, hematologic neoplasms, hematologic malignancies, primary immune deficiences, allogeneic stem cell transplant
Eligibility Criteria
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.
Sites / Locations
- Children's Hospital Los Angeles
- Stanford University - Division of Pediatric Stem Cell Transplant & Regenerative Medicine
- Children's National Medical Center
- Children's Healthcare of Atlanta
- Dana-Farber Boston Children's Cancer and Blood Disorders Center
- Children's Hospital at Montefiore
- Oregon Health Sciences University - Doernbecher Children's Hospital
- University of Texas Southwestern-Children's Medical Center
- Baylor College of Medicine/ Texas Children's Hospital
- Fred Hutchinson Cancer Research Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
BPX-501 T cells and Rimiducid
Arm Description
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.
Outcomes
Primary Outcome Measures
Adverse Event
Demonstrate safety of BPX-501 MTD
TRM/NRM
Assess the cumulative incidence of non-relapse/transplant related mortality
Secondary Outcome Measures
Disease-free survival
Disease-free survival rates after transplantation
Relapse
Cumulative incidence of relapse
Engraftment
Cumulative incidence of neutrophil and platelet engraftment, primary & secondary graft failure
GvHD
Cumulative incidence and severity of acute and chronic GvHD
Rimiducid Efficacy
Time to resolution of acute or chronic GvHD after administration of rimiducid
Infection
Rate of infectious complications
Hospitalizations
Duration of hospitalization and rehospitalization
Full Information
NCT ID
NCT03301168
First Posted
September 29, 2017
Last Updated
July 10, 2022
Sponsor
Bellicum Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT03301168
Brief Title
Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
Official Title
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 Type
Interventional
2. Study Status
Record Verification Date
May 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
April 2014 (Actual)
Primary Completion Date
May 11, 2021 (Actual)
Study Completion Date
May 2034 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bellicum Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief 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).
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia, Leukemia, Acute Myeloid (AML), Child, Lymphoma, Non-Hodgkin, Myelodysplastic Syndromes, Primary Immune Deficiency Disorder, Osteopetrosis, Cytopenia, Hemoglobinopathy in Children, Anemia, Aplastic
Keywords
ALL, AML, hematologic neoplasms, hematologic malignancies, primary immune deficiences, allogeneic stem cell transplant
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
120 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
BPX-501 T cells and Rimiducid
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
BPX-501 T cells
Other Intervention Name(s)
rivogenlecleucel
Intervention Description
T cells transduced with CaspaCIDe® safety switch
Intervention Type
Drug
Intervention Name(s)
Rimiducid
Other Intervention Name(s)
AP1903
Intervention Description
administered to inactivate BPX-501 cells in the event of GVHD
Primary Outcome Measure Information:
Title
Adverse Event
Description
Demonstrate safety of BPX-501 MTD
Time Frame
Month 24
Title
TRM/NRM
Description
Assess the cumulative incidence of non-relapse/transplant related mortality
Time Frame
Day 180, Month 12
Secondary Outcome Measure Information:
Title
Disease-free survival
Description
Disease-free survival rates after transplantation
Time Frame
Month 24
Title
Relapse
Description
Cumulative incidence of relapse
Time Frame
Month 12
Title
Engraftment
Description
Cumulative incidence of neutrophil and platelet engraftment, primary & secondary graft failure
Time Frame
Month 24
Title
GvHD
Description
Cumulative incidence and severity of acute and chronic GvHD
Time Frame
Month 24
Title
Rimiducid Efficacy
Description
Time to resolution of acute or chronic GvHD after administration of rimiducid
Time Frame
Month 24
Title
Infection
Description
Rate of infectious complications
Time Frame
Month 24
Title
Hospitalizations
Description
Duration of hospitalization and rehospitalization
Time Frame
Month 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
26 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bellicum Pharmaceuticals
Organizational Affiliation
Bellicum Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Children's Hospital Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
Stanford University - Division of Pediatric Stem Cell Transplant & Regenerative Medicine
City
Palo Alto
State/Province
California
ZIP/Postal Code
94304
Country
United States
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Dana-Farber Boston Children's Cancer and Blood Disorders Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
Children's Hospital at Montefiore
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Oregon Health Sciences University - Doernbecher Children's Hospital
City
Portland
State/Province
Oregon
ZIP/Postal Code
97239
Country
United States
Facility Name
University of Texas Southwestern-Children's Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
77390
Country
United States
Facility Name
Baylor College of Medicine/ Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Fred Hutchinson Cancer Research Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
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