Description:
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).
Title
- 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
Clinical Trial IDs
- ORG STUDY ID:
BP-U-004
- NCT ID:
NCT03301168
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
Interventions
Drug | Synonyms | Arms |
---|
BPX-501 T cells | rivogenlecleucel | BPX-501 T cells and Rimiducid |
Rimiducid | AP1903 | BPX-501 T cells and Rimiducid |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
BPX-501 T cells and Rimiducid | Experimental | 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. | |
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.
Maximum Eligible Age: | 26 Years |
Minimum Eligible Age: | 1 Month |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Adverse Event |
Time Frame: | Month 24 |
Safety Issue: | |
Description: | Demonstrate safety of BPX-501 MTD |
Secondary Outcome Measures
Measure: | Disease-free survival |
Time Frame: | Month 24 |
Safety Issue: | |
Description: | Disease-free survival rates after transplantation |
Measure: | Relapse |
Time Frame: | Month 12 |
Safety Issue: | |
Description: | Cumulative incidence of relapse |
Measure: | Engraftment |
Time Frame: | Month 24 |
Safety Issue: | |
Description: | Cumulative incidence of neutrophil and platelet engraftment, primary & secondary graft failure |
Measure: | GvHD |
Time Frame: | Month 24 |
Safety Issue: | |
Description: | Cumulative incidence and severity of acute and chronic GvHD |
Measure: | Rimiducid Efficacy |
Time Frame: | Month 24 |
Safety Issue: | |
Description: | Time to resolution of acute or chronic GvHD after administration of rimiducid |
Measure: | Infection |
Time Frame: | Month 24 |
Safety Issue: | |
Description: | Rate of infectious complications |
Measure: | Hospitalizations |
Time Frame: | Month 24 |
Safety Issue: | |
Description: | Duration of hospitalization and rehospitalization |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Active, not recruiting |
Lead Sponsor: | Bellicum Pharmaceuticals |
Trial Keywords
- ALL
- AML
- hematologic neoplasms
- hematologic malignancies
- primary immune deficiences
- allogeneic stem cell transplant
Last Updated
October 5, 2020