NCT02935257Active, not recruitingPhase 1
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
Source: ClinicalTrials.gov · Last updated 23 Sept 2025 · Not updated for over 12 months - ask the site whether it is still open
Brief summary (registry, in English)
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.
- Status (registry)
- Active, not recruiting
- Phase (registry)
- Phase 1
- Study type
- Interventional
- Enrollment
- 72 (actual)
- First submitted
- 14 Oct 2016
- Start date
- 29 Sept 2017
- Primary completion date
- 15 Aug 2024
- Lead sponsor
- University College, London
- NCT number
- NCT02935257
What you commit to
- Study type: Interventional · Phase 1
- Participants enrolled: 72
- From 29 Sept 2017 to the primary completion date, 15 Aug 2024
- 1 site in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- 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
- 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
- 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
- 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
- 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
- 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
Other illness
- CD19 negative disease
- Isolated extramedullary disease (B-ALL and CLL)
- Active hepatitis B, C or HIV infection
- Pre-existing neurological disorders (other than CNS involvement of underlying haemato-logical malignancy)
- Severe intercurrent infection at the time of scheduled CD19CAR T-cell infusion
- Severe intercurrent infection at the time of scheduled CD19CAR T-cell infusion
Lab values
- Bilirubin \>2 x upper limit of normal
- GFR \<50ml/min
- Known allergy to albumin or DMSO
- Significant cardiac disease, left ventricular ejection fraction \<40% and uncontrolled cardiac arrhythmias (patients with rate-controlled atrial fibrillation are not excluded)
Other
- B-ALL and CLL: overt CNS involvement (i.e.: patients with CNS2 with neurological symp-toms or patients with CNS3; appendix 2)
- DLBCL, FL, MCL and CLL/SLL: primary or secondary CNS lymphoma
- Oxygen saturation ≤ 90% on air
- Women who are pregnant or breast feeding
- Inability to tolerate leucapheresis
- Karnofsky score \<60% (see appendix 3)
- Patients who have experienced significant neurotoxicity following blinatumomab
- Life expectancy \<3months
- Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19CAR T-cell infusion
- Requirement for supplementary oxygen or active pulmonary infiltrates at the time of scheduled CD19CAR T-cell infusion
- Grade 3-4 CRS and or grade 3-4 neurotoxicity following Day 0 CD19CAR T-cell dose
Who the study is looking for
- 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
Age in the registry: 16 years to - · Sex: All · Does not accept healthy volunteers
Sites (1)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| University College London Hospital Coordinator of this site? Confirm its status | London | United Kingdom | Unknown status |
This page is information, not medical advice. Discuss any trial with your doctor.