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

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

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.

Study Overview

• Status: Terminated
• Conditions: Hemoglobinopathies; Hemophagocytic Lymphohistiocytosis; Metabolic Disorders; Primary Immune Deficiency Disorders; Inherited Bone Marrow Failure Syndrome
• Intervention / Treatment: Biological: BPX-501 and Rimiducid

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
• Enrollment (Actual): 1
• Phase: Phase 1

Expanded Access

No longer available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer ResearchCenter

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months to 55 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	24 months
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	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
Rimiducid Activity	Time to resolution of acute and chronic GvHD following administration of Rimiducid	Month 24
Infection Rates	Determine the risk for severe infections	Day 200
Graft Rejection	Incidence of graft rejection	Month 24
High Grade Toxicity	Rate of high grade toxicity	Month 24

Collaborators and Investigators

• Sponsor: Bellicum Pharmaceuticals
• Investigators: Study Director: Bellicum Pharmaceuticals Senior Director, Clinical Development

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): January 1, 2018

Study Registration Dates

• First Submitted: August 28, 2014
• First Submitted That Met QC Criteria: September 2, 2014
• First Posted (Estimated): September 4, 2014

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Thalassemia; Sickle Cell Disease; Chronic Granulomatous Disease; Fanconi Anemia; Mucopolysaccharidosis; Diamond Blackfan Anemia; Severe Combined Immune Deficiency; Dyskeratosis Congenita; Shwachman Diamond Syndrome; Sphingolipidoses; Congenital T-cell Defect; Congenital T-cell Deficiency
• Additional Relevant MeSH Terms: Immune System Diseases; Lymphatic Diseases; Bone Marrow Diseases; Hematologic Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Cytopenia; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases; Metabolic Diseases; Hemoglobinopathies; Lymphohistiocytosis, Hemophagocytic; Bone Marrow Failure Disorders; Pancytopenia; Congenital Bone Marrow Failure Syndromes
• Other Study ID Numbers: BP-003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No