Autologous T-cells transduced with lentiviral vector expressing a chimeric antigen receptor directed against CD19 for CD19-positive relapsed/refractory B-cell acute lymphoblastic leukaemia (B-ALL) | Diffuse large B-cell lymphoma (DLBCL) | Primary mediastinal B-cell lymphoma (PML)

Inclusion criteria

• {"criterion_text":"- Procurement eligibility 1. Diagnosis of CD19 expressing B acute lymphoblastic leukemia (ALL) or diffuse large Bcell lymphoma (DLBCL) or primary mediastinal lymphoma (PML) and one of the following: a. Patients in 1st relapse, with High-Risk (HR) features including: MLLrearrangements, E2A/TCF3-PBX1 [t(1;19)], TCF3-HLF [t(17;19)], hypodiploidy (i.e., <44 chromosomes), TP53 alterations, early (i.e., <30 months from diagnosis)/very early (i.e., <18 months from diagnosis) isolated or combined bone marrow relapse b. MRD > 0.1% after either reinduction therapy or any course of consolidation for relapsed ALL c. Patients with DLBCL or PML in 1st or subsequent relapse, after at least one standard frontline chemotherapy\n- Procurement eligibility 2. Age: 1 year – 25 years for BCP-ALL and 1-35 years for B-NHL.\n- Procurement eligibility 3. Adequate venous access for apheresis or eligible for appropriate catheter placement, and no other contraindications for leukapheresis\n- Procurement eligibility 4. Voluntary informed consent is given. For subjects < 18 year-old their legal guardian must give informed consent. Pediatric subjects will be included in age-appropriate discussion and verbal assent will be obtained for those greater than or equal to 12 years of age, when appropriate.\n- Procurement eligibility 5. Clinical performance status: Patients > 16 years of age: Karnofsky greater than or equal to 60%; Patients < 16 years of age: Lansky scale greater than or equal to 60%.\n- Treatment eligibility (i.e., eligibility to drug product infusion) 1. Diagnosis of CD19 expressing B-ALL or DLBCL or PML and one of the following: a. Patients in 1st relapse, with High-Risk (HR) features including: MLLrearrangements, E2A/TCF3-PBX1, TCF3-HLF [t(17;19)], hypodiploidy (i.e., <44 chromosomes), TP53 alterations, early (i.e., <30 months from diagnosis)/very early (i.e., <18 months from diagnosis) isolated or combined bone marrow relapse b. MRD > 0.1% after either reinduction therapy or any course of consolidation for relapsed c. Patients with DLBCL or PML in 1st or subsequent relapse, after at least one standard frontline chemotherapy\n- Treatment eligibility 2. Age: 1 year – 25 years for Bcp-ALL and 1-35 years for B-NHL.\n- Treatment eligibility 3. Voluntary informed consent is given. For subjects < 18 year-old their legal guardian must give informed consent. Pediatric subjects will be included in age-appropriate discussion and verbal assent will be obtained for those greater than or equal to 12 years of age, when appropriate.\n- Treatment eligibility 4. Clinical performance status: Patients > 16 years of age: Karnofsky greater than or equal to 60%; Patients < 16 years of age: Lansky scale greater than or equal to 60%.\n- Treatment eligibility 5. Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen.\n- Treatment eligibility 6. Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus."}

Exclusion criteria

• {"criterion_text":"- Procurement eligibility 1. Severe, uncontrolled active infections\n- Procurement eligibility 2. HIV, or active HCV and/or HBV infection (detection of viral RNA/DNA in blood)\n- Procurement eligibility 3. Previous allogeneic HSCT in the preceding 100 days before apheresis\n- Procurement eligibility 4. Concurrent or recent prior therapies, before apheresis: a) Systemic steroids (at a dose equivalent to or greater 2 mg/kg prednisone) in the 2 weeks before apheresis collection. Recent or current use of inhaled/topical/nonabsorbable steroids is not exclusionary. b) Systemic chemotherapy in the 2 weeks preceding apheresis collection. c) Anti-thymocyte globulin (ATG) in the 4 weeks preceding apheresis collection. d) Immunosuppressive agents in the 2 weeks preceding apheresis collection. e) Radiation therapy must have been completed at least 1 week prior to apheresis. f) Other anti-neoplastic investigational agents currently administered or within 30 days prior to apheresis (i.e., start of protocol therapy);\n- Treatment eligibility 1. Pregnant or lactating women\n- Treatment eligibility 2. Severe, uncontrolled active infections\n- Treatment eligibility 3. HIV, or active HCV and/or HBV infection (detection of viral RNA/DNA in blood)\n- Treatment eligibility 4. Life-expectancy < 6 weeks\n- Treatment eligibility 5. Hepatic function: Inadequate liver function defined as total bilirubin > 4x upper limit of normal (ULN) or transaminase (ALT and AST) > 6 x ULN\n- Treatment eligibility 6. Renal function: serum creatinine > 3x ULN for age.\n- Treatment eligibility 7. Blood oxygen saturation < 90%.\n- Treatment eligibility 8. Cardiac function: Left ventricular ejection fraction lower than 45% by ECHO.\n- Treatment eligibility 9. Congestive heart failure, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject.\n- Treatment eligibility 10. BM blasts > 50% pre-infusion.\n- Treatment eligibility 11. Hyperleukocytosis (greater than or equal to 20,000 blasts/microliter) or rapidly progressive disease that in the evaluation of the investigator would compromise ability to complete study therapy\n- Treatment eligibility 12. Presence of active, grade 2-4 acute or moderate-severe chronic GvHD\n- Treatment eligibility 13. Recurrent or refractory ALL with testicular involvement\n- Treatment eligibility 14. Concurrent or recent prior therapies, before infusion: a) Systemic steroids (at a dose > 2 mg/kg prednisone) in the 2 weeks before infusion. Recent or current use of inhaled/topical/non-absorbable steroids is not exclusionary. b) Systemic chemotherapy in the week preceding infusion. c) Anti-thymocyte globulin (ATG) in the 4 weeks preceding infusion. d) Immunosuppressive agents in the 1 week preceding infusion. e) Radiation therapy must have been completed at least 3 weeks prior to enrollment. f) Other anti-neoplastic investigational agents currently administered or within 30 days prior to infusion (i.e. start of protocol therapy);\n- Treatment eligibility 15. Patient-derived CD19-CAR_Lenti production failure: vitality of the fresh product <80%, CD3+ cells <80%, CD3+ CAR+ cells <10%, non-sterility in IPC at day 5, endotoxin contamination (> 5 EU/ml) in IPC at day 5, mycoplasma contamination in IPC at day 5, failure of the visual inspection."}

Primary endpoints

• {"endpoint_text":"- PHASE I The safety and tolerability of CD19-CAR_Lenti will be assessed by: - Suspected adverse events, and - Suspected serious adverse events As evidenced by clinically relevant: - Changes in clinical laboratory tests (clinical chemistry, hematology, etc). - Changes in vital signs (blood pressure, pulse, respiratory rate and body temperature). - Changes in physical examination. Signs and symptoms assessed may require additional testing as clinically indicated such as ECG, PFT, radiographic studi","definition_or_measurement_approach":"Safety and tolerability assessed by suspected adverse events and suspected serious adverse events as evidenced by clinically relevant changes in clinical laboratory tests (clinical chemistry, hematology, etc), changes in vital signs (blood pressure, pulse, respiratory rate and body temperature), changes in physical examination; additional testing as clinically indicated (e.g. ECG, PFT, radiographic studies)."}

Secondary endpoints

• {"endpoint_text":"- Secondary Endpoints phase I and II Relapse rate (RR), overall survival (OS), and disease-free survival (DFS) will be evaluated at 1 and 2 years.\n- The expansion and persistence of CD19-CAR_Lenti will be measured by flow cytometry and qPCR.\n- The T cell subpopulations of the CD19-CAR_Lenti cells before and after infusion and the exhaustion profile will be measured by flow cytometry\n- Disease outcome will be correlated with: a) use of either steroids and/or tocilizumab for CRS/Neurotoxicity; b) pr","definition_or_measurement_approach":"Relapse rate, OS, DFS evaluated at 1 and 2 years. Expansion and persistence measured by flow cytometry and qPCR. T-cell subpopulations and exhaustion profile measured by flow cytometry. Disease outcome correlations with use of steroids and/or tocilizumab for CRS/Neurotoxicity (text truncated in source)."}

Italy

Earliest CTIS Part Ii Submission Date

30-10-2024

Latest Decision Or Authorization Date

14-01-2025

Processing Time Days

76

Number Of Sites

1

Number Of Participants

32

Primary sponsor

Full Name

Ospedale Pediatrico Bambino Gesu

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Third parties

• {"country":"Germany","full_name":"Miltenyi Biotec GmbH","duties_or_roles":"Source of monetary support","organisation_type":""}