Clinical trial NCT02231710: Safety Study of Gene Modified Donor T Cell Infusion After Stem Cell Transplant for Non-Malignant Diseases
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Primary Immune Deficiency Disorders
Hemophagocytic Lymphohistiocytosis
Inherited Bone Marrow Failure Syndrome
Hemoglobinopathies
Metabolic Disorders
Keywords: 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
Lead sponsor: Bellicum Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2014-09-04
Enrollment: 1
Sex: ALL
Minimum age (years): 4
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Patient must meet eligibility criteria for allogeneic transplantation
2. 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
3. Males or females
4. Age \< 55 years old and \> 4 months
5. Diagnosis of a nonmalignant disorder considered treatable by HCT.
6. 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
7. If capable of reproduction, patient must agree to use contraception or abstinence to prevent pregnancy during the first year of enrollment and treatment.
8. Informed consent signed by patient (if ≥18 years old) or parent/guardian (if \<18 years old).
9. Fanconi anemia patients ONLY i) Patients must meet one of the following criteria to be eligible for this study:

   1. 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.
   2. Any patient with Fanconi anemia who requires red blood cell or platelet transfusions because of marrow failure
   3. Any patient with Fanconi anemia who has a life-threatening bone marrow failure involving a single hematopoietic lineage.

Exclusion Criteria:

1. Serious organ dysfunction
2. Pregnant or breast-feeding
3. Evidence of HIV infection
4. Bovine product allergy
5. Patients with an active infectious disease
6. Patients with Fanconi anemia with AML/MDS.

Primary outcomes:
measure: Adverse Events
timeFrame: 24 months
measure: Engraftment
timeFrame: Day 28
Secondary outcomes:
measure: GvHD
timeFrame: Month 24
measure: Immune Reconstitution
timeFrame: Month 24
measure: Infection Rates
timeFrame: Day 200
measure: Graft Rejection
timeFrame: Month 24
measure: Rimiducid Activity
timeFrame: Month 24
measure: High Grade Toxicity
timeFrame: Month 24
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer ResearchCenter
state: Washington
Study officials:
affiliation: Clinical Development
name: Bellicum Pharmaceuticals Senior Director
role: STUDY_DIRECTOR
References: