Active, not recruiting
Phase 1/2
Study of Gene Modified Donor T-cells Following TCR Alpha Beta Positive Depleted Stem Cell Transplant
Condition(s) studied
Acute Lymphoblastic LeukemiaLeukemia, Acute Myeloid (AML), ChildLymphoma, Non-HodgkinMyelodysplastic SyndromesPrimary Immune Deficiency DisorderOsteopetrosisCytopeniaHemoglobinopathy in ChildrenAnemia, Aplastic
Investigational drug(s) / intervention(s)
BPX-501 T cells: T cells transduced with CaspaCIDe® safety switch
Rimiducid: administered to inactivate BPX-501 cells in the event of GVHD
Study 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).
Eligibility
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.
Primary outcome measure(s)
- Adverse Event — Month 24
Demonstrate safety of BPX-501 MTD
- TRM/NRM — Day 180, Month 12
Assess the cumulative incidence of non-relapse/transplant related mortality
Trial sites (10)
| Facility | City | Region | Status |
| Children's Hospital Los Angeles |
Los Angeles |
California |
|
| Stanford University - Division of Pediatric Stem Cell Transplant & Regenerative Medicine |
Palo Alto |
California |
|
| Children's National Medical Center |
Washington D.C. |
District of Columbia |
|
| Children's Healthcare of Atlanta |
Atlanta |
Georgia |
|
| Dana-Farber Boston Children's Cancer and Blood Disorders Center |
Boston |
Massachusetts |
|
| Children's Hospital at Montefiore |
The Bronx |
New York |
|
| Oregon Health Sciences University - Doernbecher Children's Hospital |
Portland |
Oregon |
|
| University of Texas Southwestern-Children's Medical Center |
Dallas |
Texas |
|
| Baylor College of Medicine/ Texas Children's Hospital |
Houston |
Texas |
|
| Fred Hutchinson Cancer Research Center |
Seattle |
Washington |
|
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