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

Primary Purpose

Primary Immune Deficiency Disorders, Hemophagocytic Lymphohistiocytosis, Inherited Bone Marrow Failure Syndrome

Status

Active

Phase

Phase 1

Locations

United States

Study Type

Interventional

Intervention

BPX-501 and Rimiducid

About this trial

This is an interventional treatment trial for Primary Immune Deficiency Disorders focused on measuring 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

Eligibility Criteria

4 Months - 55 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient must meet eligibility criteria for allogeneic transplantation
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
Males or females
Age < 55 years old and > 4 months
Diagnosis of a nonmalignant disorder considered treatable by HCT.
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
If capable of reproduction, patient must agree to use contraception or abstinence to prevent pregnancy during the first year of enrollment and treatment.
Informed consent signed by patient (if ≥18 years old) or parent/guardian (if <18 years old).
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:

Serious organ dysfunction
Pregnant or breast-feeding
Evidence of HIV infection
Bovine product allergy
Patients with an active infectious disease
Patients with Fanconi anemia with AML/MDS.

Sites / Locations

Fred Hutchinson Cancer ResearchCenter

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BPX-501 and Rimiducid

Arm Description

Single administration of BPX-501 T cells post partially-mismatched, related T cell depleted HCT followed by Rimiducid infusion on day 7

Outcomes

Primary Outcome Measures

Adverse Events

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

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

GvHD

To determine the incidence and severity of acute and chronic GVHD

Immune Reconstitution

Measure immune reconstitution

Infection rates

Determine the risk for severe infections

Graft rejection

Incidence of graft rejection

Rimiducid Activity

Time to resolution of acute and chronic GvHD following administration of Rimiducid

High grade toxicity

Rate of high grade toxicity

Full Information

NCT ID

NCT02231710

First Posted

August 28, 2014

Last Updated

July 10, 2022

Sponsor

Bellicum Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02231710

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

Study Type

Interventional

2. Study Status

Record Verification Date

July 2022

Overall Recruitment Status

Active, not recruiting

Study Start Date

February 2015 (Actual)

Primary Completion Date

July 2017 (Actual)

Study Completion Date

July 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bellicum Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

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

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

1 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BPX-501 and Rimiducid

Arm Type

Experimental

Arm Description

Single administration of BPX-501 T cells post partially-mismatched, related T cell depleted HCT followed by Rimiducid infusion on day 7

Intervention Type

Biological

Intervention Name(s)

BPX-501 and Rimiducid

Intervention Description

Single administration of BPX-501 T cells post partially-mismatched, related T cell depleted HCT followed by Rimiducid infusion on day 7

Primary Outcome Measure Information:

Title

Adverse Events

Description

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

Time Frame

Month 24

Title

Engraftment

Description

Time Frame

Day 28

Secondary Outcome Measure Information:

Title

GvHD

Description

To determine the incidence and severity of acute and chronic GVHD

Time Frame

Month 24

Title

Immune Reconstitution

Description

Measure immune reconstitution

Time Frame

Month 24

Title

Infection rates

Description

Determine the risk for severe infections

Time Frame

Day 200

Title

Graft rejection

Description

Incidence of graft rejection

Time Frame

Month 24

Title

Rimiducid Activity

Description

Time to resolution of acute and chronic GvHD following administration of Rimiducid

Time Frame

Month 24

Title

High grade toxicity

Description

Rate of high grade toxicity

Time Frame

Month 24

10. Eligibility

Sex

All

Minimum Age & Unit of Time

4 Months

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patient must meet eligibility criteria for allogeneic transplantation 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 Males or females Age < 55 years old and > 4 months Diagnosis of a nonmalignant disorder considered treatable by HCT. 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 If capable of reproduction, patient must agree to use contraception or abstinence to prevent pregnancy during the first year of enrollment and treatment. Informed consent signed by patient (if ≥18 years old) or parent/guardian (if <18 years old). Fanconi anemia patients ONLY i) Patients must meet one of the following criteria to be eligible for this study: 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. Any patient with Fanconi anemia who requires red blood cell or platelet transfusions because of marrow failure Any patient with Fanconi anemia who has a life-threatening bone marrow failure involving a single hematopoietic lineage. Exclusion Criteria: Serious organ dysfunction Pregnant or breast-feeding Evidence of HIV infection Bovine product allergy Patients with an active infectious disease Patients with Fanconi anemia with AML/MDS.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bellicum Pharmaceuticals Senior Director

Organizational Affiliation

Clinical Development

Official's Role

Study Director

Facility Information:

Facility Name

Fred Hutchinson Cancer ResearchCenter

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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