- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02065869
Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
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 Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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Roma, Italy, 00161
- IRCCS Ospedale Pediatrico Bambino Gesu
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London, United Kingdom, NW3 2QG
- Royal Free London NHS Foundation Trust
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London, United Kingdom, WC1N 1EH
- Institute of Child Health & Great Ormond Street Hospital
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Newcastle Upon Tyne, United Kingdom, NE1 4LP
- Great North Children's Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: BPX-501 T cells and rimiducid
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 |
1x10E6 cells/kg infused on Day 0
Other Names:
0.4mg/kg administered IV to treat GVHD
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Event-free Survival (EFS) at 180 Days After Transplant
Time Frame: 180 days after transplant
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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
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Bellicum Pharmaceuticals, Bellicum Pharmaceuticals, Inc.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Immunologic Deficiency Syndromes
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Bone Marrow Diseases
- Hematologic Diseases
- Genetic Diseases, Inborn
- Musculoskeletal Diseases
- Bone Diseases
- DNA Repair-Deficiency Disorders
- Leukemia, Lymphoid
- Anemia, Hemolytic, Congenital
- Anemia, Hemolytic
- Anemia, Hypoplastic, Congenital
- Congenital Bone Marrow Failure Syndromes
- Bone Marrow Failure Disorders
- Lymphoma
- Bone Diseases, Developmental
- Osteochondrodysplasias
- Leukemia, Myeloid
- Red-Cell Aplasia, Pure
- Osteosclerosis
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid, Acute
- Lymphoma, Non-Hodgkin
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Primary Immunodeficiency Diseases
- Anemia
- Anemia, Sickle Cell
- Fanconi Anemia
- Thalassemia
- Anemia, Aplastic
- Hemoglobinopathies
- Anemia, Diamond-Blackfan
- Osteopetrosis
Other Study ID Numbers
- BP-004
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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Bellicum PharmaceuticalsActive, not recruiting
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Bellicum PharmaceuticalsNo longer availableHurler Syndrome | Inborn Errors of Metabolism | Metachromatic Leukodystrophy | Inherited Metabolic Disorder | Lysosomal Storage DisorderUnited States
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Bellicum PharmaceuticalsActive, not recruitingLymphoma | Myelodysplastic Syndromes | Acute Lymphoblastic Leukemia | Acute Myelogenous LeukemiaUnited States
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Bellicum PharmaceuticalsTerminatedHemoglobinopathies | Hemophagocytic Lymphohistiocytosis | Metabolic Disorders | Primary Immune Deficiency Disorders | Inherited Bone Marrow Failure SyndromeUnited States
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Bellicum PharmaceuticalsWithdrawnHematologic MalignanciesUnited States
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Rapa Therapeutics LLCMassachusetts General Hospital; Hackensack Meridian HealthAvailable
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Bellicum PharmaceuticalsTerminatedLymphoma, Non-Hodgkin | Myelodysplastic Syndromes | Acute Lymphoblastic Leukemia | Primary Immunodeficiency | Anemia, Sickle Cell | Hemoglobinopathies | Fanconi Anemia | Anemia, Aplastic | Thalassemia | Cytopenia | Diamond Blackfan Anemia | Leukemia, Acute Myeloid (AML), ChildItaly