Safety Study of Gene Modified Donor T Cell Infusion After Stem Cell Transplant for Non-Malignant Diseases

Study Overview
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Brief Summary
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The purpose of this study is to determine a safe dose of BPX-501 gene modified T cells infused after a haplo-identical stem cell transplant to facilitate engraftment and the safety of Rimiducid (AP1903) on day 7 to prevent GVHD.

Detailed Description
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This is a single arm dose finding study evaluating the safety and efficacy of a BPX 501 infusion (T cells genetically modified with the inducible Caspase 9 suicide gene) of 3x10E6 to 1X10E7 cells/kg followed by a Rimiducid infusion on day 7 after a partially mismatched, related, T cell-depleted hematopoietic cell transplantation (HCT) in patients with non-malignant diseases. The purpose of this clinical trial is to determine the dose of BPX 501 T cell infusion with subsequent planned infusion of Rimiducid which can facilitate engraftment and prevent the occurrence of GVHD.

Official Title
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A Study Evaluating BPX-501 T Cells and AP1903 for Prevention of Graft Versus Host Disease (GVHD) After Haploidentical, Related, T Cell-Depleted Hematopoietic Cell Transplantation for Non-Malignant Diseases

Conditions
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Primary Immune Deficiency Disorders, Hemophagocytic Lymphohistiocytosis, Inherited Bone Marrow Failure Syndrome, Hemoglobinopathies, Metabolic Disorders

Intervention / Treatment
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* Biological: BPX-501 and Rimiducid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must meet eligibility criteria for allogeneic transplantation Lack of suitable conventional donor (10/10 allele matched related or unrelated donor) or presence of rapidly progressive disease not permitting time to identify an unrelated donor Males or females Age < 55 years old and > 4 months Diagnosis of a nonmalignant disorder considered treatable by HCT. HLA typing will be performed at high resolution (allele level) for the HLA-A, -B, Cw, DRBl, and DQB1 loci. i. A minimum match of 5/10 is required. ii. The donor and recipient must be identical, as determined by high resolution typing, in at least one allele of each of the following If capable of reproduction, patient must agree to use contraception or abstinence to prevent pregnancy during the first year of enrollment and treatment. Informed consent signed by patient (if ≥18 years old) or parent/guardian (if <18 years old). Fanconi anemia patients ONLY i) Patients must meet one of the following criteria to be eligible for this study: Any patient with Fanconi anemia and bone marrow failure involving 2 of the following 3 lineages: granulocyte count <0.5 x 109/L, platelet count <20 x 109/L, or hemoglobin <8 g/dL. Any patient with Fanconi anemia who requires red blood cell or platelet transfusions because of marrow failure Any patient with Fanconi anemia who has a life-threatening bone marrow failure involving a single hematopoietic lineage. Exclusion Criteria: Serious organ dysfunction Pregnant or breast-feeding Evidence of HIV infection Bovine product allergy Patients with an active infectious disease Patients with Fanconi anemia with AML/MDS.

Ages Eligible for Study
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Minimum Age: 4 Months
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BPX-501 and Rimiducid<br>Single administration of BPX-501 T cells post partially-mismatched, related T cell depleted HCT followed by Rimiducid infusion on day 7 | Biological: BPX-501 and Rimiducid<br>* Single administration of BPX-501 T cells post partially-mismatched, related T cell depleted HCT followed by Rimiducid infusion on day 7<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Determine the safety of HCT with HLA-haploidentical CD34+ selected peripheral blood stem cell (PBSC) grafts and BPX 501 T cells followed by scheduled AP1903 infusion | Month 24 | 
| Engraftment | Determine the engraftment rate (defined as >50% donor CD3 chimerism) on day 28 after HCT with HLA-haploidentical CD34+ selected PBSC grafts per dose cohort of BPX 501 T cells followed by Rimiducid infusion on Day 7. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GvHD | To determine the incidence and severity of acute and chronic GVHD | Month 24 | 
| Immune Reconstitution | Measure immune reconstitution | Month 24 | 
| Infection rates | Determine the risk for severe infections | Day 200 | 
| Graft rejection | Incidence of graft rejection | Month 24 | 
| Rimiducid Activity | Time to resolution of acute and chronic GvHD following administration of Rimiducid | Month 24 | 
| High grade toxicity | Rate of high grade toxicity | Month 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe Combined Immune Deficiency, Congenital T-cell Defect, Congenital T-cell Deficiency, Chronic Granulomatous Disease, Shwachman Diamond Syndrome, Diamond Blackfan Anemia, Dyskeratosis Congenita, Fanconi Anemia, Sickle Cell Disease, Thalassemia, Mucopolysaccharidosis, Sphingolipidoses