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

Hemoglobinopathies Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02231710
• Other study ID #: BP-003
• Status: Terminated
• Phase: Phase 1
• Start date: February 2015
• Est. completion date: January 2018

Study information

• Verified date: September 2023
• Source: Bellicum Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: January 2018
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Months to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Bone Marrow Failure Disorders
• Congenital Bone Marrow Failure Syndromes
• Hemoglobinopathies
• Hemophagocytic Lymphohistiocytosis
• Immunologic Deficiency Syndromes
• Inherited Bone Marrow Failure Syndrome
• Lymphohistiocytosis, Hemophagocytic
• Metabolic Diseases
• Metabolic Disorders
• Pancytopenia
• Primary Immune Deficiency Disorders
• Primary Immunodeficiency Diseases

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

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer ResearchCenter	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Bellicum Pharmaceuticals

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	24 months
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	Day 28
Secondary	GvHD	To determine the incidence and severity of acute and chronic GVHD	Month 24
Secondary	Immune Reconstitution	Measure immune reconstitution	Month 24
Secondary	Infection Rates	Determine the risk for severe infections	Day 200
Secondary	Graft Rejection	Incidence of graft rejection	Month 24
Secondary	Rimiducid Activity	Time to resolution of acute and chronic GvHD following administration of Rimiducid	Month 24
Secondary	High Grade Toxicity	Rate of high grade toxicity	Month 24