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 II Extension Study of CaspaCIDe T Cells (BPX-501) 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 | | BPX-501 T cells and AP1903 |
AP1903 | rimiducid | BPX-501 T cells and AP1903 |
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 2 extension 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 AP1903 | Experimental | TCR alpha beta depleted graft infusion with addback of BPX-501 T cells.
AP1903: 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. 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: | non-relapse/transplant related mortality (TRM/NRM) |
Time Frame: | 1 year |
Safety Issue: | |
Description: | To maintain the cumulative incidence of non-relapse/transplant related mortality (TRM/NRM) at 1 year in subjects given the MTD defined during the Phase I portion of the study comparable to that of a historical cohort of subjects given the alpha/beta T-cell depleted HSCT without any T-cell add-back (i.e., below 10%) |
Secondary Outcome Measures
Measure: | Disease-free survival |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Disease-free survival rates after transplantation |
Measure: | Relapse |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Cumulative incidence of relapse |
Measure: | acute GVHD |
Time Frame: | 1 year |
Safety Issue: | |
Description: | Cumulative incidence and severity of acute GVHD |
Measure: | chronic GVHD |
Time Frame: | 2 years |
Safety Issue: | |
Description: | Cumulative incidence and severity of chroonic GVHD |
Measure: | Kinetics of donor cell engraftment |
Time Frame: | 3 times per week after transplant until the neutrophil count reaches 0.5 x 10E9/L. Thereafter, at least 2 times per week until the neutrophil count is > 1.0 x 10E9/L and platelets > 100 x 10E9/L. |
Safety Issue: | |
Description: | time to hematopoietic recovery defined as: neutrophils > 0.5 x 10E9/L for 3 consecutive days together with platelet count > 20 x 10E9/L and without platelet support for 7 consecutive days |
Details
Phase: | Phase 1/Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Bellicum Pharmaceuticals |
Trial Keywords
- ALL
- AML
- hematologic neoplasms
- hematologic malignancies
- primary immune deficiences
- allogeneic stem cell transplant
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