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).
Brief Title
Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
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.
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.
Categories
Completion Date
Completion Date Type
Estimated
Conditions
Acute Lymphoblastic Leukemia
Leukemia, Acute Myeloid (AML), Child
Lymphoma, Non-Hodgkin
Myelodysplastic Syndromes
Primary Immune Deficiency Disorder
Osteopetrosis
Cytopenia
Hemoglobinopathy in Children
Anemia, Aplastic
Eligibility Criteria
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.
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.
Inclusion Criteria
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
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
Gender
All
Gender Based
false
Keywords
ALL
AML
hematologic neoplasms
hematologic malignancies
primary immune deficiences
allogeneic stem cell transplant
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Maximum Age
26 Years
Minimum Age
1 Month
NCT Id
NCT03301168
Org Class
Industry
Org Full Name
Bellicum Pharmaceuticals
Org Study Id
BP-U-004
Overall Status
Active, not recruiting
Phases
Phase 1
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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
Primary Outcomes
Outcome Description
Demonstrate safety of BPX-501 MTD
Outcome Measure
Adverse Event
Outcome Time Frame
Month 24
Outcome Description
Assess the cumulative incidence of non-relapse/transplant related mortality
Outcome Measure
TRM/NRM
Outcome Time Frame
Day 180, Month 12
Secondary Outcomes
Outcome Description
Disease-free survival rates after transplantation
Outcome Time Frame
Month 24
Outcome Measure
Disease-free survival
Outcome Description
Cumulative incidence of relapse
Outcome Time Frame
Month 12
Outcome Measure
Relapse
Outcome Description
Cumulative incidence of neutrophil and platelet engraftment, primary \& secondary graft failure
Outcome Time Frame
Month 24
Outcome Measure
Engraftment
Outcome Description
Cumulative incidence and severity of acute and chronic GvHD
Outcome Time Frame
Month 24
Outcome Measure
GvHD
Outcome Description
Time to resolution of acute or chronic GvHD after administration of rimiducid
Outcome Time Frame
Month 24
Outcome Measure
Rimiducid Efficacy
Outcome Description
Rate of infectious complications
Outcome Time Frame
Month 24
Outcome Measure
Infection
Outcome Description
Duration of hospitalization and rehospitalization
Outcome Time Frame
Month 24
Outcome Measure
Hospitalizations
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Child
Adult
Locked Fields
Render the field
Maximum Age Number (converted to Years and rounded down)
26
Minimum Age Number (converted to Years and rounded down)
0
Investigators
Investigator Type
Principal Investigator
Investigator Name
Michelle Lee
Investigator Email
miclee@montefiore.org