B Acute Lymphoblastic LeukemiaPhase 1PBLTT52CAR19NCT04557436
TT52CAR19 Therapy for B-cell Acute Lymphoblastic Leukaemia (B-ALL)
A Phase 1 study testing PBLTT52CAR19 in people with B Acute Lymphoblastic Leukemia, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
PBLTT52CAR19 modified T cells are allogenic engineered human T cells (defined as TT52CAR19 +TCRαβ-) prepared for the treatment of CD19+ B cell leukaemia. The cells are from healthy adult volunteer donors and are not HLA-matched. Read more about this study
- Who is it for?
- Ages 6 months to 18 years
- Conditions the study is for
- B Acute Lymphoblastic Leukemia
- What is being tested?
- PBLTT52CAR19
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 12 Aug 2020to 5 Mar 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 6 months to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Patients with relapsed (second or subsequent bone marrow relapse or bone marrow relapse after allo-SCT) or refractory (not achieving an initial complete response (CR) after 2 cycles of standard chemotherapy) CD19-positive B-acute lymphoblastic leukaemia
- Morphologically confirmed with leukemic blasts in the bone marrow or a quantifiable MRD load of 1x10-4 (by multiparameter flow cytometry and/or quantitative polymerase chain reaction)
- Eligible and fit for allogeneic hematopoietic stem cells transplantation with suitable donor available
- Estimated life expectancy ≥ 12 weeks
- Lansky (age < 16 years at the time of assent/consent) or Karnofsky (age ≥ 16 years at the time of assent/consent) performance status ≥ 50 Eastern Cooperative Oncology Group ECOG performance status < 2
Who cannot join
- Patients/parents unwilling to undergo a follow-up for 15 years
- Foreseeable poor compliance to the study procedures
- CD19-negative B-cell leukaemia
- Evidence of disease progression after cytoreduction
- Uncontrollable CNS leukaemia or neurological symptoms defined as CNS grade 3 (per National Comprehensive Cancer National guidelines). Patients developing grade 3 CNS disease at any time after enrolment will be excluded.
- Absence of suitable HLA matched or mismatched donor
Show all 18Show fewer
- Weight < 6 kgs
- Presence of donor-specific anti-HLA antibodies directed against PBLTT52CAR19
- GvHD requiring systemic therapy
- Systemic steroid therapy prednisolone >0.5mg/kg/day
- Known hypersensitivity to any of the test materials or related compounds
- Active bacterial, fungal, or viral infection not controlled by a standard of care anti-microbial or anti-viral treatment. Uncontrolled bacteraemia/ fungaemia is defined as the ongoing detection of bacteria/fungus on blood cultures despite antibiotic or anti-fungal therapy.
- Uncontrolled viraemia is defined as rising viral loads on two consecutive occasions despite antiviral therapy.
- Risk of pregnancy or non-compliance with contraception (if applicable). Girls of childbearing potential must have been tested negative in a pregnancy test within 14 days prior to inclusion.
- Lactating female participants unwilling to stop breastfeeding
- Intrathecal methotrexate within 4 weeks or intrathecal chemotherapy (e.g Ara-C) within 2 weeks of lymphodepletion
- Less than 2 half-lives from prior therapy with immune checkpoint pathway modifiers to lymphodepletion
- Prior CAR19 therapy known to be associated with ≥Grade 3 cytokine release syndrome (CRS) or ≥Grade 3 drug-related CNS toxicity
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase 1, Open Label Study of CRISPR-CAR Genome Edited T Cells (PBLTT52CAR19) in Relapsed /Refractory B Cell Acute Lymphoblastic Leukaemia
PBLTT52CAR19 modified T cells are allogenic engineered human T cells (defined as TT52CAR19 +TCRαβ-) prepared for the treatment of CD19+ B cell leukaemia. The cells are from healthy adult volunteer donors and are not HLA-matched. They have been transduced to express and anti-CD19 chimeric antigen receptor (CAR19) using a lentiviral vector that also incorporates CRISPR guides for genome editing of CD52 and TRAC loci in the presence of transiently provided Cas9.
Recognition by TT52CAR19 T cells mediates eradication of CD19+ leukaemia and other CD19+ B cells through T cell mediated cytotoxicity.
This study aims to apply PBLTT52CAR19 T cells to secure molecular remission in children with relapsed/refractory B-ALL ahead of programmed allogeneic stem cell transplantation. The cells are to be used in a time-limited manner for their anti-leukaemia effects and then depleted by standard pre- transplant conditioning.
- Conditions
- B Acute Lymphoblastic Leukemia
- Being tested
- PBLTT52CAR19
- Keywords
- relapsed, refractory
- Medical subject headings
- Burkitt Lymphoma, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PBLTT52CAR19Drug
gene therapy
| Study group | Role | What they receive |
|---|---|---|
| Standard of care | Other | Follow-up period:
For patients achieving molecular remission by day 28, allo-HSCT will be scheduled as soon as practicable. Routine transplant care for 24 months will incorporate the disease monitoring and recording of adverse events of special interest and document elimination of PBLTT52CAR19 through the transplant conditioning period.
For patients with refractory disease at Day 56, the monitoring of adverse events of special interest, the disease outcome will be monitored monthly up to 24 months or until a palliative therapy approach is adopted.
Assessments will be carried out after the treatment period at the following time points: 1m, 2m, 3m, 6m, and 12m, 24m
* Physical examination, ECOG
* Laboratory tests
* Vital signs (temperature, BP, HR, respiratory rate, weight)
* Persistence of PBLTT52CAR19, VCN by qPCR in blood and bone marrow (if sampled)
* Chimerism and MRD in blood and bone marrow (if sampled)
* Adverse events
* Concomitant treatments Receives: Drug: PBLTT52CAR19 |
What is being measured
The primary outcome is the main question the study is designed to answer.
B-ALL remission
The main benefit expected from PBLTT52CAR19 for anti-CD19 activity leading to anti-leukemic effect and induction of remission in children with refractory/relapsed B-ALL. Patients who achieve molecular remission will become eligible to receive an allo-HSCT that would otherwise be considered futile.Remission of B-cell acute lymphoblastic leukaemia (B-ALL) in anticipation of a haematopoietic stem cell transplant (HSCT that would otherwise be considered futile.
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2020
- Study start12 Aug 2020
- Primary completion5 Mar 2024
- Study completion5 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for B 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
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is an open label, single-centre, phase I, cohort study using genome edited T cells to bring patients with relapsed or refractory B-cell acute lymphoblastic leukaemia (B-ALL) into remission in anticipation of a haematopoietic stem cell transplant (HSCT) that will hopefully prevent the leukaemia from returning. It involves a single infusion of allogenic T cells transduced with a self-inactivating (SIN) lentiviral vector in up to 10 subjects aged from 6 months to 18 years. The primary objective in this study is to test the safety and secondary objective will test the efficacy of this gene therapy procedure in this population. Patients will be enrolled following diagnosis and referral to GOSH, and will receive TT52CAR19 cells at GOSH after lymphodepleting conditioning. They will be followed on this protocol for 12 months post IMP infusion.
- Masking
- None (open label)
- Enrolment
- 9 participants (actual)
Sponsor and investigators
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation Trust
- Sponsor type
- University, hospital or other
- Collaborators
- University College, London
- Responsible party
- Sponsor
- Investigators
- Waseem Qasim, Prof, Principal investigator, UCL GOSH Institute of Child HealthPaul Veys, PhD, MD, Study director, Great Ormond Street HospitalKanchan Rao, PhD, MD, Study director, Great Ormond Street HospitalAjay Vora, Prof, MD, Study director, Great Ormond Street Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04557436
- Sponsor's protocol ID
- 18IC07
- Acronym
- PBLTT52CAR19
- Status last verified
- Mar 2024
- First submitted
- 15 Sep 2020
- Last updated
- 7 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ottaviano G, Georgiadis C, Gkazi SA, Syed F, Zhan H, Etuk A, Preece R, Chu J, Kubat A, Adams S, Veys P, Vora A, Rao K, Qasim W; TT52 CRISPR-CAR group. Phase 1 clinical trial of CRISPR-engineered CAR19 universal T cells for treatment of children with refractory B cell leukemia. Sci Transl Med. 2022 Oct 26;14(668):eabq3010. doi: 10.1126/scitranslmed.abq3010. Epub 2022 Oct 26.
PubMed 36288281
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1, Open Label Study of CRISPR-CAR Genome Edited T Cells (PBLTT52CAR19) in Relapsed /Refractory B Cell Acute Lymphoblastic Leukaemia
- ClinicalTrials.gov ID
- NCT04557436
- Acronym / sponsor ID
- PBLTT52CAR19 / 18IC07
- Conditions
- B Acute Lymphoblastic Leukemia
- Keywords
- relapsed, refractory
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Great Ormond Street Hospital for Children NHS Foundation TrustUniversity, hospital or other
- Collaborators
- University College, London
- Study start
- 12 Aug 2020 (actual)
- Primary completion
- 5 Mar 2024 (actual)
- Study completion
- 5 Mar 2024 (actual)
- First posted
- 21 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
PBLTT52CAR19 modified T cells are allogenic engineered human T cells (defined as TT52CAR19 +TCRαβ-) prepared for the treatment of CD19+ B cell leukaemia. The cells are from healthy adult volunteer donors and are not HLA-matched. They have been transduced to express and anti-CD19 chimeric antigen receptor (CAR19) using a lentiviral vector that also incorporates CRISPR guides for genome editing of CD52 and TRAC loci in the presence of transiently provided Cas9.
Recognition by TT52CAR19 T cells mediates eradication of CD19+ leukaemia and other CD19+ B cells through T cell mediated cytotoxicity.
This study aims to apply PBLTT52CAR19 T cells to secure molecular remission in children with relapsed/refractory B-ALL ahead of programmed allogeneic stem cell transplantation. The cells are to be used in a time-limited manner for their anti-leukaemia effects and then depleted by standard pre- transplant conditioning.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is an open label, single-centre, phase I, cohort study using genome edited T cells to bring patients with relapsed or refractory B-cell acute lymphoblastic leukaemia (B-ALL) into remission in anticipation of a haematopoietic stem cell transplant (HSCT) that will hopefully prevent the leukaemia from returning. It involves a single infusion of allogenic T cells transduced with a self-inactivating (SIN) lentiviral vector in up to 10 subjects aged from 6 months to 18 years. The primary objective in this study is to test the safety and secondary objective will test the efficacy of this gene therapy procedure in this population. Patients will be enrolled following diagnosis and referral to GOSH, and will receive TT52CAR19 cells at GOSH after lymphodepleting conditioning. They will be followed on this protocol for 12 months post IMP infusion.
| Arm | Type | Receives |
|---|---|---|
| Standard of care | Other | Drug: PBLTT52CAR19Follow-up period: For patients achieving molecular remission by day 28, allo-HSCT will be scheduled as soon as practicable. Routine transplant care for 24 months will incorporate the disease monitoring and recording of adverse events of special interest and document elimination of PBLTT52CAR19 through the transplant conditioning period. For patients with refractory disease at Day 56, the monitoring of adverse events of special interest, the disease outcome will be monitored monthly up to 24 months or until a palliative therapy approach is adopted. Assessments will be carried out after the treatment period at the following time points: 1m, 2m, 3m, 6m, and 12m, 24m * Physical examination, ECOG * Laboratory tests * Vital signs (temperature, BP, HR, respiratory rate, weight) * Persistence of PBLTT52CAR19, VCN by qPCR in blood and bone marrow (if sampled) * Chimerism and MRD in blood and bone marrow (if sampled) * Adverse events * Concomitant treatments |
Who may qualify
- Ages
- 6 months to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Patients with relapsed (second or subsequent bone marrow relapse or bone marrow relapse after allo-SCT) or refractory (not achieving an initial complete response (CR) after 2 cycles of standard chemotherapy) CD19-positive B-acute lymphoblastic leukaemia
- Morphologically confirmed with leukemic blasts in the bone marrow or a quantifiable MRD load of 1x10-4 (by multiparameter flow cytometry and/or quantitative polymerase chain reaction)
- Eligible and fit for allogeneic hematopoietic stem cells transplantation with suitable donor available
- Estimated life expectancy ≥ 12 weeks
- Lansky (age < 16 years at the time of assent/consent) or Karnofsky (age ≥ 16 years at the time of assent/consent) performance status ≥ 50 Eastern Cooperative Oncology Group ECOG performance status < 2
Key exclusion criteria (18 listed)
- Patients/parents unwilling to undergo a follow-up for 15 years
- Foreseeable poor compliance to the study procedures
- CD19-negative B-cell leukaemia
- Evidence of disease progression after cytoreduction
- Uncontrollable CNS leukaemia or neurological symptoms defined as CNS grade 3 (per National Comprehensive Cancer National guidelines). Patients developing grade 3 CNS disease at any time after enrolment will be excluded.
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 |
|---|---|---|
| PBLTT52CAR19gene therapy | Drug | Standard of care |
Primary outcome
B-ALL remission
Time frame: 28 days
The main benefit expected from PBLTT52CAR19 for anti-CD19 activity leading to anti-leukemic effect and induction of remission in children with refractory/relapsed B-ALL. Patients who achieve molecular remission will become eligible to receive an allo-HSCT that would otherwise be considered futile.Remission of B-cell acute lymphoblastic leukaemia (B-ALL) in anticipation of a haematopoietic stem cell transplant (HSCT that would otherwise be considered futile.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2024.
- Derived from this study: PubMed 36288281Ottaviano G, Georgiadis C, Gkazi SA, Syed F, Zhan H, Etuk A, Preece R, Chu J, Kubat A, Adams S, Veys P, Vora A, Rao K, Qasim W; TT52 CRISPR-CAR group. Phase 1 clinical trial of CRISPR-engineered CAR19 universal T cells for treatment of children with refractory B cell leukemia. Sci Transl Med. 2022 Oct 26;14(668):eabq3010. doi: 10.1126/scitranslmed.abq3010. Epub 2022 Oct 26.
- Individual participant dataSharing planned: No
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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.
Waseem Qasim, Prof principal investigator
UCL GOSH Institute of Child Health
Paul Veys, PhD, MD study director
Great Ormond Street Hospital
Kanchan Rao, PhD, MD study director
Great Ormond Street Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PBLTT52CAR19 in people with B Acute Lymphoblastic Leukemia, run by Great Ormond Street Hospital for Children NHS Foundation Trust at 1 site in United Kingdom.
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 5 inclusion and 18 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: finished, as of the sponsor's last update on 7 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
B-ALL remission (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04557436, which also lists 1 linked publication.
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 7 Mar 2024.