Hemoglobinopathies, Hemophagocytic Lymphohistiocytosis, Inherited Bone Marrow Failure Syndrome, Metabolic Disorders, Primary Immune Deficiency Disorders
Conditions
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
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.
Interventions
BIOLOGICALBPX-501 and Rimiducid
Single administration of BPX-501 T cells post partially-mismatched, related T cell depleted HCT followed by Rimiducid infusion on day 7
Sponsors
Bellicum Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
4 Months to 55 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 24 months | To determine the safety (as defined by non-responsive Grade III-IV GVHD to rimiducid) of HCT with HLA-haploidentical CD34+ selected peripheral blood stem cell (PBSC) grafts and BPX 501 T cells followed by scheduled rimiducid infusion on Day 7. this outcome measure is reported as number of patients who experienced the AE of Grade III-IV GVHD that was not non-responsive to rimiducid (safety switch) administration. |
| Engraftment | Day 28 | 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. NOTE: only one patient was enrolled who received the dose of 5x 10\^6cell/kg dose of BPX-501 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Infection Rates | Day 200 | Determine the risk for severe infections |
| Graft Rejection | Month 24 | Incidence of graft rejection |
| GvHD | Month 24 | To determine the incidence and severity of acute and chronic GVHD |
| High Grade Toxicity | Month 24 | Rate of high grade toxicity |
| Rimiducid Activity | Month 24 | Time to resolution of acute and chronic GvHD following administration of Rimiducid |
| Immune Reconstitution | Month 24 | Measure immune reconstitution |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BPX-501 and Rimiducid Single administration of BPX-501 T cells (5 x 10\^6 cell/kg), post partially-mismatched, related T cell depleted HCT followed by Rimiducid infusion on day 7
BPX-501 and Rimiducid: Single administration of BPX-501 T cells post partially-mismatched, related T cell depleted HCT followed by Rimiducid infusion on day 7
NOTE: This study enrolled a single patient and was terminated early due to lack of enrolment | 1 |
| Total | 1 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Physician Decision | 1 |
Baseline characteristics
| Characteristic | BPX-501 and Rimiducid | — |
|---|---|---|
| Age, Continuous | 12 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 1 participants | — |
| Sex: Female, Male Female | 0 Participants | — |
| Sex: Female, Male Male | 1 Participants | — |
| sickle cell disease | 1 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Adverse Events
To determine the safety (as defined by non-responsive Grade III-IV GVHD to rimiducid) of HCT with HLA-haploidentical CD34+ selected peripheral blood stem cell (PBSC) grafts and BPX 501 T cells followed by scheduled rimiducid infusion on Day 7. this outcome measure is reported as number of patients who experienced the AE of Grade III-IV GVHD that was not non-responsive to rimiducid (safety switch) administration.
Time frame: 24 months
Population: One subject was dosed with 5 x 106 cells of BPX-501 T cells and 0.4 mg/kg of rimiducid on Day 7. No efficacy data was gathered for this patient and patient was withdrawn from the Study by investigator's physician. The study was terminated early by Sponsor due to lack of enrolment
Primary
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. NOTE: only one patient was enrolled who received the dose of 5x 10\^6cell/kg dose of BPX-501
Time frame: Day 28
Population: One subject was dosed with 5 x 106 cells of BPX-501 T cells and 0.4 mg/kg of rimiducid on Day 7. No efficacy data was gathered for this patient and patient was withdrawn from the Study by investigator's physician. The study was terminated early by Sponsor due to lack of enrolment
Secondary
Graft Rejection
Incidence of graft rejection
Time frame: Month 24
Secondary
GvHD
To determine the incidence and severity of acute and chronic GVHD
Time frame: Month 24
Secondary
High Grade Toxicity
Rate of high grade toxicity
Time frame: Month 24
Secondary
Immune Reconstitution
Measure immune reconstitution
Time frame: Month 24
Secondary
Infection Rates
Determine the risk for severe infections
Time frame: Day 200
Secondary
Rimiducid Activity
Time to resolution of acute and chronic GvHD following administration of Rimiducid
Time frame: Month 24