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

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Primary Immune Deficiency Disorders; Hemophagocytic Lymphohistiocytosis; Inherited Bone Marrow Failure Syndrome; Hemoglobinopathies; Metabolic Disorders	Biological: BPX-501 and Rimiducid	Phase 1

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: February 2015
• Actual Primary Completion Date: July 2017
• Estimated Study Completion Date: July 2030

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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
2. 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.

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 4 Months to 55 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Washington

Fred Hutchinson Cancer ResearchCenter

Seattle, Washington, United States, 98109

Sponsors and Collaborators

Bellicum Pharmaceuticals

Investigators

• Study Director: Bellicum Pharmaceuticals Senior Director; Clinical Development

More Information

• Responsible Party: Bellicum Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT02231710
• Other Study ID Numbers: BP-003
• First Posted: September 4, 2014
• Last Update Posted: July 12, 2022
• Last Verified: July 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

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

Keywords provided by Bellicum Pharmaceuticals:

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

Additional relevant MeSH terms:

Bone Marrow Failure Disorders; Pancytopenia; Hemoglobinopathies; Lymphohistiocytosis, Hemophagocytic; Congenital Bone Marrow Failure Syndromes; Primary Immunodeficiency Diseases; Metabolic Diseases; Immunologic Deficiency Syndromes; Disease; Pathologic Processes; Immune System Diseases; Bone Marrow Diseases; Hematologic Diseases; Genetic Diseases, Inborn; Histiocytosis, Non-Langerhans-Cell; Histiocytosis; Lymphatic Diseases; Infant, Newborn, Diseases