Immunotherapy for High Risk/Relapsed CD19+ Acute Lymphoblastic Leukaemia, B-cell Non-Hodgkin's Lymphoma (B-NHL) and Chronic Lymphocytic Leukaemia (CLL)/ Small Lymphocytic Lymphoma (SLL) Using CAR T-cells to Target CD19 (ALLCAR19)

September 18, 2025 updated by: University College, London

This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age ≥16) with (1) high risk, relapsed/refractory (r/r) CD19+ B-ALL; (2) r/r DLBCL; (3) r/r CLL/SLL and (4) r/r FL and (5) r/r MCL. The ATIMP for this study is cryopreserved autologous patient-derived T-cells transduced with the lentiviral pCCL.PGK.alpha.CD19CAT-41BBzeta vector, CD19CAT-41BBζ CAR T-cells (referred to subsequently as CD19CAR T-cells) which is classified as a gene therapy medicinal product. Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP. The ATIMP will take approximately 15 days to generate. During this period, patients may receive "holding" chemotherapy as per institutional practice to maintain disease control. The study will evaluate ATIMP safety and efficacy and the duration of disease response in adults with high risk / relapsed CD19+ B-ALL, DLBCL, B-CLL/SLL, FL and MCL.

Recruitment into the ALL cohort has been completed and no further patients with ALL are being treated on the study.

Patients receive pre-conditioning lymphodepleting chemotherapy with cyclophosphamide 60mg/kg on Day -6 and fludarabine 30mg/m2 administered over 3 days (Day -5 to Day -3). Patients with DLBCL only will also receive a single dose of pembrolizumab 200 mg at day -1.

Patients recruited to ALLCAR19 are treated with different dosing schedules, depending on their underlying disease. Patients with B-ALL and B-CLL/SLL are considered at high risk of CLL/CRES so receive split dosing, with the second dose only given in the absence of severe toxicity 9 days later. CAR T-cell dosing in ALLCAR19 is flat i.e. not dependent on patient body weight or surface area.

  • Regimen A1: Patients with B-ALL with a baseline marrow blast% of ≤20% receive a split dose with a first dose of 100 x 10^6 CD19 CAR T-cells and a possible second dose of 310 x 106 CAR T-cells
  • Regimen A2: Patients with B-ALL with a baseline marrow blast% of >20% receive a split dose with a first dose of 10 x 10^6 CD19CAR T-cells and a possible second dose of 400 x 10^6 CAR T-cells
  • Regimen B: Patients with DLBCL receive a single dose of 200 x 10^6 CAR T-cells
  • Regimen C: Patients with CLL/SLL will receive a split dose with a first dose of 30 x 106 CD19 CAR T-cells and a possible second dose of 200 x 10^6 CD19 CAR T-cells.
  • Regimen D: Patients with FL and MCL receive a single dose of 200 x 10^6 CAR T-cells

The study evaluates ATIMP feasibility and safety of generating CD19CAR T-cells and for B-ALL patients only, efficacy and the duration of disease response to CD19CAR T-cells.

After completing the interventional phase of the study all patients, irrespective of whether they progressed or responded to treatment, enter long term follow up until 10 years post-CD19CAR T-cell infusion.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a multi-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age ≥16) with (1) high risk, relapsed/refractory (r/r) CD19+ B-ALL; (2) r/r DLBCL; (3) r/r CLL/SLL, (4) r/r FL and (5) r/r MCL. The ATIMP for this study is cryopreserved autologous patient-derived T-cells transduced with the lentiviral pCCL.PGK.alpha.CD19CAT-41BBζ vector, CD19CAT-41BBζ CAR T-cells (referred to sub-sequently as CD19CAR T-cells) which is classified as a gene therapy medicinal product. Patients will undergo an unstimulated leucapheresis for the generation of the ATIMP. The ATIMP take approximately 15 days to generate. During this period, patients may receive "holding" chemotherapy as per institutional practice to maintain disease control. The study evaluates ATIMP safety and efficacy and the duration of disease response in adults with high risk / relapsed CD19+ B-ALL, DLBCL, B-CLL/SLL, FL and MCL.

The ALL and FL cohorts are now completed and no further patients with ALL or FL are treated on the study.

Patients receive lymphodepleting chemotherapy with cyclophosphamide 60mg/kg on Day -6 and fludarabine 30mg/m2 administered over 3 days (Day -5 to Day -3). Patients with DLBCL only also receive a single dose of pembrolizumab 200 mg at day -1.

Patients recruited to ALLCAR19 are treated with different dosing schedules, depending on their underlying disease. Patients with B-ALL and B-CLL/SLL are considered at high risk of CLL/CRES so receive split dosing, with the second dose only given in the absence of severe toxicity 9 days later. CAR T-cell dosing in ALLCAR19 is flat i.e. not dependent on patient body weight or surface area.

  • Regimen A1: Patients with B-ALL with a baseline marrow blast% of ≤20% receive a split dose with a first dose of 100 x 10^6 CD19 CAR T-cells and a possible second dose of 310 x 10^6 CAR T-cells
  • Regimen A2: Patients with B-ALL with a baseline marrow blast% of >20% receive a split dose with a first dose of 10 x 10^6 CD19CAR T-cells and a possible second dose of 400 x 106 CAR T-cells
  • Regimen B: Patients with DLBCL receive a single dose of 200 x 10^6 CAR T-cells
  • Regimen C: Patients with CLL/SLL will receive a split dose with a first dose of 30 x 10^6 CD19 CAR T-cells and a possible second dose of 200 x 106 CD19 CAR T-cells.
  • Regimen D: Patients with indolent B-NHL receive a single dose of 200 x 10^6 CAR T-cells

The study evaluates ATIMP feasibility and safety of generating CD19CAR T-cells and for B-ALL patients only, efficacy and the duration of disease response to CD19CAR T-cells.

After completing the interventional phase of the study all patients, irrespective of whether they progressed or responded to treatment, will enter long term follow up until 10 years post-CD19CAR T-cell infusion.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
72

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United Kingdom
      • London, United Kingdom
        • University College London Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

16 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

1. Age ≥162. B-ALL: high risk or relapsed histologically confirmed CD19+ B-ALL following standard therapy requiring salvage in whom alternative therapies are deemed inappropriate by their treating physician Or DLBCL: relapsed/refractory DLBCL (incl. transformed FL but not Richter's transformation) following ≥2 prior lines of therapy including Rituximab and anthracycline Or CLL/SLL: relapsed/refractory CLL/SLL following ≥2 prior lines of therapy including Ibrutinib or other Bruton's Tyrosine Kinase (BTK) inhibitors Or Follicular Lymphoma which is relapsed / refractory following ≥2 prior lines of therapy Or Mantle Cell Lymphoma which is relapsed / refractory following ≥2 prior lines of therapy 3. Agreement to have a pregnancy test, use adequate contraception (if applicable) 4.Written informed consent

Exclusion criteria for registration:

  1. CD19 negative disease
  2. B-ALL and CLL: overt CNS involvement (i.e.: patients with CNS2 with neurological symp-toms or patients with CNS3; appendix 2)
  3. DLBCL, FL, MCL and CLL/SLL: primary or secondary CNS lymphoma
  4. Isolated extramedullary disease (B-ALL and CLL)
  5. Active hepatitis B, C or HIV infection
  6. Oxygen saturation ≤ 90% on air
  7. Bilirubin >2 x upper limit of normal
  8. GFR <50ml/min
  9. Women who are pregnant or breast feeding
  10. Stem Cell Transplant patients only: active significant acute GVHD (overall Grade ≥ II, Seattle criteria) or moderate/severe chronic GVHD (NIH consensus criteria) requiring im-munosuppressive therapy and/or systemic steroids
  11. Inability to tolerate leucapheresis
  12. Karnofsky score <60% (see appendix 3)
  13. Patients who have experienced significant neurotoxicity following blinatumomab
  14. Known allergy to albumin or DMSO
  15. Life expectancy <3months
  16. Significant cardiac disease, left ventricular ejection fraction <40% and uncontrolled cardiac arrhythmias (patients with rate-controlled atrial fibrillation are not excluded)
  17. Pre-existing neurological disorders (other than CNS involvement of underlying haemato-logical malignancy)

  18. DLBCL only:

    • Any contraindications to PD-1 antibody Pembrolizumab
    • History of autoimmune disease (e.g. Crohn's, rheumatoid arthritis, systemic lupus) re-sulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 24 months
    • Evidence of active pneumonitis on chest computed tomography (CT) scan at screening or history of drug-induced pneumonitis, idiopathic pulmonary fibrosis, organising pneu-monia (e.g. bronchiolitis obliterans), or idiopathic pneumonitis. Prior radiation pneu-monitis in the radiation field (fibrosis) is allowed (if >24 weeks since the event)
    • Chest/mediastinal radiation within 24 weeks of CAR T-cellinfusion

Exclusion criteria: for CD19CAR T-cell infusion at Day 0 (all patients):

  1. Severe intercurrent infection at the time of scheduled CD19CAR T-cell infusion
  2. Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19CAR T-cell infusion
  3. Allogeneic transplant recipients with active significant acute GVHD overall grade ≥II or moderate/severe chronic GVHD requiring systemic steroids or other immunosuppres-sion at the time of scheduled CD19CAR T-cell infusion. Note: Such patients will be ex-cluded until the patient is GVHD free and off steroids

Exclusion criteria: for supplementary CD19CAR T-cell infusion Day 9 (B-ALL and CLL/SLL patients):

  1. Severe intercurrent infection at the time of scheduled CD19CAR T-cell infusion
  2. Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19CAR T-cell infusion
  3. Grade 3-4 CRS and or grade 3-4 neurotoxicity following Day 0 CD19CAR T-cell dose
  4. Grade 1-2 neurotoxicity (if occurred) following Day 0 CD19CAR T-cell dose that has not fully resolved prior to proposed administration of 2nd CD19CAR T-cell dose
  5. Persisting Grade 2 CRS following Day 0 CD19CAR T-cell dose that has not resolved to ≤ Grade 1 CRS prior to proposed administration of 2nd CD19CAR T-cell dose
  6. Allogeneic transplant recipients with active significant acute GVHD overall grade ≥II or moderate/severe chronic GVHD requiring systemic steroids or other immunosuppression at the time of scheduled CD19CAR T-cell infusion* *Note: Such patients will be excluded until the patient is GVHD free and off steroids

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: CD19CAT-41BBZ CAR T-cells
Treatment with the ATIMP: CD19CAT-41BBZ CAR T-cells
Biological: CD19CAT-41BBZ CAR T-cells
Infusion with CD19CAT-41BBZ CAR T-cells

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Toxicity evaluated by the incidence of grade 3-5 toxicity causally related to the ATIMP
Time Frame: 28 days
Toxicity following CD19CAR T-cell administration as evaluated by the incidence of grade 3-5 toxicity causally related to the ATIMP.
28 days
Feasibility of manufacturing CD19CAR T-cells evaluated by the number of therapeutic products generated
Time Frame: 30 days
Feasibility of adequate leucapheresis collection and generation of CAR19 T cells as evaluated by the number of therapeutic products generated.
30 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University College, London

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Karl Peggs, University College London Hospitals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 29, 2017

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 15, 2024

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2033

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 14, 2016

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 14, 2016

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 17, 2016

Study Record Updates

Last Update Posted (Estimated)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 23, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 18, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UCL/16/0530

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

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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