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

NCT02065869 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: BP-004
• Study Type: interventional
• Target: 187
• Locations: 2 countries
• Sites: 4

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).

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (1)

BPX-501 T cells and rimiducid

EXPERIMENTAL

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

Biological: BPX-501 T cells; Drug: Rimiducid

Interventions

BPX-501 T cells BIOLOGICAL

1x10E6 cells/kg infused on Day 0

Also known as: Rivogenlecleucel

BPX-501 T cells and rimiducid

Rimiducid DRUG

0.4mg/kg administered IV to treat GVHD

Also known as: AP1903

BPX-501 T cells and rimiducid

Eligibility Criteria

• Age: 1 Month - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bellicum Pharmaceuticals: lead

Study Sites (4)

IRCCS Ospedale Pediatrico Bambino Gesù

Roma, 00161, Italy

Location

Royal Free London NHS Foundation Trust

London, NW3 2QG, United Kingdom

Location

Institute of Child Health & Great Ormond Street Hospital

London, WC1N 1EH, United Kingdom

Location

Great North Children's Hospital

Newcastle upon Tyne, NE1 4LP, United Kingdom

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Myelodysplastic Syndromes; Primary Immunodeficiency Diseases; Anemia, Aplastic; Osteopetrosis; Hemoglobinopathies; Cytopenia; Fanconi Anemia; Anemia, Diamond-Blackfan; Thalassemia; Anemia, Sickle Cell; Hematologic Neoplasms; Anemia

Interventions

AP 1903 reagent

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, Myeloid; Lymphoma; Bone Marrow Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immunologic Deficiency Syndromes; Bone Marrow Failure Disorders; Osteosclerosis; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Anemia, Hypoplastic, Congenital; Congenital Bone Marrow Failure Syndromes; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Red-Cell Aplasia, Pure; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Neoplasms by Site

Results Point of Contact

• Title: Rivogenlecleucel Study Team
• Organization: Bellicum Pharmaceuticals

clinicaltrials@bellicum.com

(832) 384 1100

Study Officials

• Bellicum Pharmaceuticals

  Bellicum Pharmaceuticals, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 13, 2014
• First Posted: February 19, 2014
• Study Start: April 1, 2014
• Primary Completion: June 1, 2020
• Study Completion: September 7, 2021
• Last Updated: September 29, 2023
• Results First Posted: January 4, 2023

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); GB (3)