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

Phase 1

Terminated

• Conditions: Primary Immune Deficiency Disorders; Hemophagocytic Lymphohistiocytosis; Metabolic Disorders; Hemoglobinopathies; Inherited Bone Marrow Failure Syndrome
• Interventions: Biological: BPX-501 and Rimiducid

• Registration Number: NCT02231710
• Lead Sponsor: Bellicum Pharmaceuticals

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 Timeline

• Study First Submitted: 2014-08-28
• Study First Submitted QC: 2014-09-02
• Study First Posted: 2014-09-04
• Study Start: 2015-02
• Primary Completion: 2015-09
• Study Completion: 2018-01
• Status Verified: 2023-09
• Results First Submitted: 2023-09-22
• Results First Submitted QC: 2023-09-22
• Last Update Submitted: 2023-09-22
• Results First Posted: 2024-03-25
• Last Update Posted: 2024-03-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 1

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
BPX-501 and Rimiducid	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
GvHD	Month 24	To determine the incidence and severity of acute and chronic GVHD
Immune Reconstitution	Month 24	Measure immune reconstitution
Graft Rejection	Month 24	Incidence of graft rejection
Infection Rates	Day 200	Determine the risk for severe infections
Rimiducid Activity	Month 24	Time to resolution of acute and chronic GvHD following administration of Rimiducid
High Grade Toxicity	Month 24	Rate of high grade toxicity

Trial Locations

Locations (1)

Fred Hutchinson Cancer ResearchCenter; 🇺🇸 Seattle, Washington, United States