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

• ClinicalTrials.gov Identifier: NCT02231710
• Recruitment Status: Active, not recruiting
• First Posted: September 4, 2014
• Last Update Posted: July 12, 2022
• Sponsor: Bellicum Pharmaceuticals
• Information provided by (Responsible Party): Bellicum Pharmaceuticals

Tracking Information

• First Submitted Date: August 28, 2014
• First Posted Date: September 4, 2014
• Last Update Posted Date: July 12, 2022
• Actual Study Start Date: February 2015
• Actual Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 10, 2022)

• Adverse Events [ Time Frame: Month 24 ]
  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
• Engraftment [ Time Frame: 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.

Original Primary Outcome Measures (submitted: September 2, 2014)

GVHD [ Time Frame: day 100 ]

The incidence and Grade of acute GVHD will be determined

Current Secondary Outcome Measures (submitted: October 1, 2020)

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

• Original Secondary Outcome Measures (submitted: September 2, 2014): Transplant related mortality [ Time Frame: 6 months ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

Biological: 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

Study Arms

Experimental: 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

Intervention: Biological: BPX-501 and Rimiducid

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: January 18, 2018): 1
• Original Estimated Enrollment (submitted: September 2, 2014): 20
• Estimated Study Completion Date: July 2030
• Actual Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 4 Months to 55 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02231710
• Other Study ID Numbers: BP-003
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Bellicum Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Bellicum Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Bellicum Pharmaceuticals Senior Director; Clinical Development

• PRS Account: Bellicum Pharmaceuticals
• Verification Date: July 2022