Acute Lymphoblastic LeukemiaPhase 1/2NCT02065869
Safety Study of Gene Modified Donor T-cells Following TCRαβ+ Depleted Stem Cell Transplant
A Phase 1/2 study testing BPX-501 T cells and Rimiducid in people with Acute Lymphoblastic Leukemia and Leukemia, Acute Myeloid (AML), Child, run by Bellicum Pharmaceuticals at 4 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 1 month to 18 years
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Leukemia, Acute Myeloid (AML), Child, Lymphoma, Non-Hodgkin
- What is being tested?
- BPX-501 T cells and Rimiducid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 187 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Apr 2014to 7 Sep 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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).
Show all 12Show fewer
- 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
Who cannot join
- 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.
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United Kingdom3 sites
Royal Free London NHS Foundation Trust
London, NW3 2QG
Institute of Child Health & Great Ormond Street Hospital
London, WC1N 1EH
Great North Children's Hospital
Newcastle upon Tyne, NE1 4LP
About this study
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
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).
Read the 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.
- Conditions
- Acute Lymphoblastic Leukemia, Leukemia, Acute Myeloid (AML), Child, Lymphoma, Non-Hodgkin, Myelodysplastic Syndrome, Primary Immunodeficiency, Anemia, Aplastic
- Being tested
- BPX-501 T cells, Rimiducid
- Keywords
- ALL, AML, hematologic neoplasms, hematologic malignancies, primary immune deficiences, hemoglobinopathy, congenital cytopenia, anemia
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Leukemia, Myeloid, Acute, Lymphoma, Non-Hodgkin, Myelodysplastic Syndromes, Primary Immunodeficiency Diseases, Anemia, Aplastic, Osteopetrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BPX-501 T cellsBiological
Also called Rivogenlecleucel
1x10E6 cells/kg infused on Day 0
RimiducidDrug
Also called AP1903
0.4mg/kg administered IV to treat GVHD
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Biological: BPX-501 T cells; Drug: Rimiducid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 180 days after transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2014 (estimated)
- Study startApr 2014
- Primary completionJun 2020
- Study completion7 Sep 2021
Why it stopped: Sponsor decision
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 187 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bellicum Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bellicum Pharmaceuticals, Study director, Bellicum Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02065869
- Sponsor's protocol ID
- BP-004
- Status last verified
- Sep 2023
- First submitted
- 13 Feb 2014
- Last updated
- 29 Sep 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02065869
- Acronym / sponsor ID
- BP-004
- Conditions
- Acute Lymphoblastic Leukemia, Leukemia, Acute Myeloid (AML), Child, Lymphoma, Non-Hodgkin, Myelodysplastic Syndrome, Primary Immunodeficiency, Anemia, Aplastic
- Keywords
- ALL, AML, hematologic neoplasms, hematologic malignancies, primary immune deficiences, hemoglobinopathy, congenital cytopenia, anemia
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision
- Enrolment
- 187 participants (actual)
- Lead sponsor
- Bellicum PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- Apr 2014 (actual)
- Primary completion
- Jun 2020 (actual)
- Study completion
- 7 Sep 2021 (actual)
- First posted
- 19 Feb 2014 (estimated)
- Results
- Posted 4 Jan 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BPX-501 T cells and rimiducid | Experimental | Biological: BPX-501 T cells, Drug: RimiducidTCR 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 |
Who may qualify
- Ages
- 1 month to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (12 listed)
- 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.
Key exclusion criteria (8 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BPX-501 T cellsAlso: Rivogenlecleucel1x10E6 cells/kg infused on Day 0 | Biological | BPX-501 T cells and rimiducid |
| RimiducidAlso: AP19030.4mg/kg administered IV to treat GVHD | Drug | BPX-501 T cells and rimiducid |
Primary outcome
Event-free Survival (EFS) at 180 Days After Transplant
Time frame: 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Acute Lymphoblastic Leukemia
Active, not recruitingPhase 2
Brentuximab Vedotin and Combination Chemotherapy in Treating Patients With CD30-Positive Peripheral T-cell Lymphoma
Adult T-Cell Leukemia/Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Negative
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 2
Obesity Treatment With Phentermine-Topiramate ER in AYA Surviving Leukemia and Lymphoma
Acute Lymphoblastic Leukemia in Remission, Hodgkin Lymphoma in Remission
Recruiting
A Multicenter Study to Evaluate Next-Generation Sequencing (NGS) Testing and Monitoring of B-Cell Recovery to Guide Management Following Chimeric Antigen Receptor T-cell (CART) Induced Remission in Children and Young Adults With B Lineage Acute Lymph...
B-All, Acute Lymphoblastic Leukemia
Not yet recruitingPhase 1
A Study to Assess the Pharmacokinetics and Safety of Revumenib in Participants With Advanced Cancer and Hepatic or Renal Impairment
Relapsed/Refractory (R/R) Hematologic Malignancies, Acute Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bellicum Pharmaceuticals study director
Bellicum Pharmaceuticals
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BPX-501 T cells and Rimiducid in people with Acute Lymphoblastic Leukemia and Leukemia, Acute Myeloid (AML), Child, run by Bellicum Pharmaceuticals at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United Kingdom, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jan 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Event-free Survival (EFS) at 180 Days After Transplant (time frame: 180 days after transplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2023.