Engineered immune cells take on tough blood cancers in early trial

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

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