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

Acute Lymphoblastic Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02065869
• Other study ID #: BP-004
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: April 2014
• Est. completion date: September 7, 2021

Study information

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

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 187
• Est. completion date: September 7, 2021
• Est. primary completion date: June 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 18 Years

Eligibility

Inclusion Criteria:

1. Age < 18 years and > 1 month (< 1 month upon approval by Sponsor)

2. Life expectancy > 10 weeks

3. Patients deemed clinically eligible for allogeneic stem cell transplantation.

4. Patients may have failed prior allograft

5. 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.

6. 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 ß0 ß0 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.

7. 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

8. A minimum genotypic identical match of 5/10 is required.

9. 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.

10. Lansky/Karnofsky score > 50

11. Signed informed consent by the patient or the patient's parent or guardian for patients who are minors

Exclusion Criteria:

1. Greater than active Grade II acute GvHD or chronic extensive GvHD due to a previous allograft at the time of screening

2. Patient receiving an immunosuppressive treatment for GvHD treatment due to a previous allograft at the time of screening

3. 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)

4. Severe cardiovascular disease (arrhythmias requiring chronic treatment, congestive heart failure or left ventricular ejection fraction < 40%)

5. Current clinically active infectious disease (including positive HIV serology or viral RNA)

6. Serious concurrent uncontrolled medical disorder

7. Pregnant or breast feeding female patient

8. Lack of parents'/guardian's informed consent for children who are minors.

Related Conditions & MeSH terms

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

Intervention

Biological:
• BPX-501 T cells
1x10E6 cells/kg infused on Day 0

Drug:
• Rimiducid
0.4mg/kg administered IV to treat GVHD

Locations

Country	Name	City	State
Italy	IRCCS Ospedale Pediatrico Bambino Gesù	Roma
United Kingdom	Institute of Child Health & Great Ormond Street Hospital	London
United Kingdom	Royal Free London NHS Foundation Trust	London
United Kingdom	Great North Children's Hospital	Newcastle Upon Tyne

Sponsors (1)

Lead Sponsor	Collaborator
Bellicum Pharmaceuticals

Countries where clinical trial is conducted

Italy,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	180 days after transplant