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Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant

Primary Purpose

Acute Lymphoblastic Leukemia, Leukemia, Acute Myeloid (AML), Child, Lymphoma, Non-Hodgkin

Status

Terminated

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

BPX-501 T cells

Rimiducid

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring ALL, AML, hematologic neoplasms, hematologic malignancies, primary immune deficiences, hemoglobinopathy, congenital cytopenia, anemia

Eligibility Criteria

1 Month - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age < 18 years and > 1 month (< 1 month upon approval by Sponsor)
Life expectancy > 10 weeks
Patients deemed clinically eligible for allogeneic stem cell transplantation.
Patients may have failed prior allograft
Patients with life-threatening acute leukemia (high-risk ALL in 1st CR, ALL in 2nd CR, high-risk AML in 1st CR, AML in 2nd CR.) or myelodysplastic syndromes. Morphological CR must be documented and minimal residual disease measurement before transplantation is recommended.
Non-malignant disorders deemed curable by allogeneic transplantation: a. primary immune deficiencies, b. severe aplastic anemia not responding to immune suppressive therapy, c. osteopetrosis d. selected cases of erythroid disorders such as β0 β0 thalassemia major, sickle cell disease, Diamond-Blackfan anemia.
e. congenital/hereditary cytopenia, including Fanconi Anemia before any clonal malignant evolution (MDS, AML).

Note: Subjects will be eligible if they meet either item 5 OR item 6.

Lack of suitable conventional donor (HLA identical sibling or HLA phenotypically identical relative or 10/10 unrelated donor evaluated using high resolution molecular typing) or presence of rapidly progressive disease not permitting time to identify an unrelated donor
A minimum genotypic identical match of 5/10 is required.
The donor and recipient must be identical, as determined by high resolution typing, on at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA- DRB1 and HLA-DQB1.
Lansky/Karnofsky score > 50
Signed informed consent by the patient or the patient's parent or guardian for patients who are minors

Exclusion Criteria:

Greater than active Grade II acute GvHD or chronic extensive GvHD due to a previous allograft at the time of screening
Patient receiving an immunosuppressive treatment for GvHD treatment due to a previous allograft at the time of screening
Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance <30ml/min/1.73m2)
Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction < 40%)
Current clinically active infectious disease (including positive HIV serology or viral RNA)
Serious concurrent uncontrolled medical disorder
Pregnant or breast feeding female patient
Lack of parents'/guardian's informed consent for children who are minors.

Sites / Locations

IRCCS Ospedale Pediatrico Bambino Gesù
Royal Free London NHS Foundation Trust
Institute of Child Health & Great Ormond Street Hospital
Great North Children's Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

BPX-501 T cells and rimiducid

Arm Description

TCR alpha beta depleted graft infusion with addback of BPX-501 T cells (rivogenlecleucel). Rimiducid/AP1903: Dimerizer drug administered to subjects who develop Grade III-IV acute GVHD, Grade II gut/liver acute GVDH or Grade I/II skin-only acute GvHD which is non-responsive after 7 days of standard of care treatment

Outcomes

Primary Outcome Measures

Event-free Survival (EFS) at 180 Days After Transplant

Events included transplant-related mortality (TRM) / non-relapse mortality (NRM), severe GvHD (acute Grades 2-4 organ or extensive chronic GvHD) and life-threatening infections (Grade 4). Time to the first event only is represented in the primary endpoint, if a subsequent event occurred in the same patient this was not captured in this outcome. There were no protocol-specified primary endpoints for Phase I of the study.

Secondary Outcome Measures

Full Information

NCT ID

NCT02065869

First Posted

February 13, 2014

Last Updated

September 22, 2023

Sponsor

Bellicum Pharmaceuticals

1. Study Identification

Unique Protocol Identification Number

NCT02065869

Brief Title

Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant

Official Title

Phase I/II Study of CaspaCIDe T Cells (BPX-501; Rivogenlecleucel) From an HLA Partially Matched Family Donor After Negative Selection of TCRαβ+ T Cells in Paediatric Patients Affected by Haematological Disorders

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Terminated

Why Stopped

Sponsor decision

Study Start Date

April 2014 (Actual)

Primary Completion Date

June 2020 (Actual)

Study Completion Date

September 7, 2021 (Actual)

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

This study will evaluate pediatric patients with malignant or non-malignant blood cell disorders who are having a blood stem cell transplant depleted of T cell receptor (TCR) alfa and beta cells that comes from a partially matched family donor. The study will assess whether immune cells, called T cells, from the family donor, that are specially grown in the laboratory and given back to the patient along with the stem cell transplant can help the immune system recover faster after transplant. As a safety measure these T cells have been programmed with a self-destruct switch so that they can be destroyed if they start to react against tissues (Graft versus host disease).

Detailed Description

This is a Phase I/II study evaluating the safety and feasibility of BPX-501 T cells infused after partially mismatched, related, TCR alpha beta T cell depleted hematopoietic stem cell transplant (HSCT) in pediatric patients. The purpose of this clinical trial is to determine whether BPX-501 infusion can enhance immune reconstitution in those patients with hematologic disorders, with the potential for reducing the severity and duration severe acute graft versus host disease (GvHD). The trial will also evaluate the treatment of GvHD by the infusion of dimerizer drug (AP1903/rimiducid) in those subjects who present with GVHD who progress or do not respond to standard of care treatment.

6. Conditions and Keywords

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

Acute Lymphoblastic Leukemia, Leukemia, Acute Myeloid (AML), Child, Lymphoma, Non-Hodgkin, Myelodysplastic Syndrome, Primary Immunodeficiency, Anemia, Aplastic, Osteopetrosis, Hemoglobinopathies, Cytopenia, Fanconi Anemia, Diamond Blackfan Anemia, Thalassemia, Anemia, Sickle Cell

Keywords

ALL, AML, hematologic neoplasms, hematologic malignancies, primary immune deficiences, hemoglobinopathy, congenital cytopenia, anemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

187 (Actual)

8. Arms, Groups, and Interventions

Arm Title

BPX-501 T cells and rimiducid

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

BPX-501 T cells

Other Intervention Name(s)

Rivogenlecleucel

Intervention Description

1x10E6 cells/kg infused on Day 0

Intervention Type

Drug

Intervention Name(s)

Rimiducid

Other Intervention Name(s)

AP1903

Intervention Description

0.4mg/kg administered IV to treat GVHD

Primary Outcome Measure Information:

Title

Event-free Survival (EFS) at 180 Days After Transplant

Description

Time Frame

180 days after transplant

10. Eligibility

Sex

All

Minimum Age & Unit of Time

1 Month

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age < 18 years and > 1 month (< 1 month upon approval by Sponsor) Life expectancy > 10 weeks Patients deemed clinically eligible for allogeneic stem cell transplantation. Patients may have failed prior allograft Patients with life-threatening acute leukemia (high-risk ALL in 1st CR, ALL in 2nd CR, high-risk AML in 1st CR, AML in 2nd CR.) or myelodysplastic syndromes. Morphological CR must be documented and minimal residual disease measurement before transplantation is recommended. Non-malignant disorders deemed curable by allogeneic transplantation: (a) primary immune deficiencies, (b) severe aplastic anemia not responding to immune suppressive therapy, (c) osteopetrosis, (d) selected cases of erythroid disorders such as β0 β0 thalassemia major, sickle cell disease, Diamond-Blackfan anemia, (e) congenital/hereditary cytopenia, including Fanconi Anemia before any clonal malignant evolution (MDS, AML). Note: Subjects will be eligible if they meet either item 5 OR item 6. Lack of suitable conventional donor (HLA identical sibling or HLA phenotypically identical relative or 10/10 unrelated donor evaluated using high resolution molecular typing) or presence of rapidly progressive disease not permitting time to identify an unrelated donor A minimum genotypic identical match of 5/10 is required. The donor and recipient must be identical, as determined by high resolution typing, on at least one allele of each of the following genetic loci: HLA-A, HLA-B, HLA-Cw, HLA- DRB1 and HLA-DQB1. Lansky/Karnofsky score > 50 Signed informed consent by the patient or the patient's parent or guardian for patients who are minors Exclusion Criteria: Greater than active Grade II acute GvHD or chronic extensive GvHD due to a previous allograft at the time of screening Patient receiving an immunosuppressive treatment for GvHD treatment due to a previous allograft at the time of screening Dysfunction of liver (ALT/AST > 5 times normal value, or bilirubin > 3 times normal value), or of renal function (creatinine clearance <30ml/min/1.73m2) Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction < 40%) Current clinically active infectious disease (including positive HIV serology or viral RNA) Serious concurrent uncontrolled medical disorder Pregnant or breast feeding female patient Lack of parents'/guardian's informed consent for children who are minors.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bellicum Pharmaceuticals

Organizational Affiliation

Bellicum Pharmaceuticals, Inc.

Official's Role

Study Director

Facility Information:

Facility Name

IRCCS Ospedale Pediatrico Bambino Gesù

City

Roma

ZIP/Postal Code

00161

Country

Italy

Facility Name

Royal Free London NHS Foundation Trust

City

London

ZIP/Postal Code

NW3 2QG

Country

United Kingdom

Facility Name

Institute of Child Health & Great Ormond Street Hospital

City

London

ZIP/Postal Code

WC1N 1EH

Country

United Kingdom

Facility Name

Great North Children's Hospital

City

Newcastle Upon Tyne

ZIP/Postal Code

NE1 4LP

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant

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