Overview

Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant

Status:
Active, not recruiting
Trial end date:
2034-05-01
Target enrollment:
0
Participant gender:
All
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).
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Bellicum Pharmaceuticals
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.