AUTOLOGOUS PERIPHERAL BLOOD-DERIVED CD4 AND CD8 T LYMPHOCYTES, TRANSDUCED WITH A LENTIVIRAL VECTOR TO EXPRESSING A CHIMERIC RECEPTOR AGAINST BCMA WITH CO-STIMULATORY SEQUENCES 4-1-BB AND CD3 ZETA for Multiple myeloma

Inclusion criteria

• {"criterion_text":"- 1. Patients > 18 years old with a diagnosis of post-allogeneic transplant relapse multiple myeloma.\n- 2. Medical illness\n- 3. Previous treatment with 2 lines before and/or after allogeneic transplant.\n- 4. Patients who are not receiving immunosuppressants at least 1 month before inclusion and who do not have active GVHD.\n- 5. ECOG functional status from 0 to 1.\n- 6. Life expectancy greater than 3 months\n- 7. Patients who give their consent by signing the Informed Consent document."}

Exclusion criteria

• {"criterion_text":"- 1. Active systemic immunosuppressive therapy.\n- 2. Patients who have previously received CAR-T Anti-BCMA treatment. Patients who have received another type of anti-BCMA therapy will not be excluded, although in this case the positivity for BCMA in myeloma cells must be confirmed at the time of inclusion.\n- 3. Absolute lymphocyte count <0.2x109/L.\n- 4. Previous malignancy, except if in complete remission >3 years, with the exception of cutaneous carcinoma (non-melanoma).\n- 5. Active infection requiring treatment.\n- 6. Active HIV, HBV, or HCV infection.\n- 7. Uncontrolled medical illness.\n- 8. Severe organic disease that meets any of the following criteria: EF <40%, DLCO < 40%, GFR < 50 ml/min, bilirubin > 3 NV (except Gilbert's syndrome).\n- 9. Previous diagnosis of symptomatic AL amyloidosis or POEMS syndrome.\n- 10. Pregnant or lactating women.\n- 11. Women of childbearing potential who are unable or unwilling to use highly effective contraceptive methods\n- 12. Men unable or unwilling to use highly effective contraceptive methods\n- 13. Contraindication to receive lymphodepletive chemotherapy."}

Primary endpoints

• {"endpoint_text":"- Primary feasibility variable: Number of cases in which the manufacturing process is completed and HUVR-CARTemis-1 cells are infused.","definition_or_measurement_approach":"Count of cases where manufacturing is completed and HUVR-CARTemis-1 cells are successfully infused."}
• {"endpoint_text":"- Safety variables: Maximum tolerated dose of HUVR-CARTemis-1 determined based on the incidence in different patient cohorts of the following toxicities: Rate of patients developing cytokine release syndrome and/or neurological toxicity and/or macrophage activation. Rate of patients developing graft-versus-recipient disease - Patients developing grade 3-4 toxicities that do not respond to standard treatment. Presence of infusional reactions. -Presence of SAEs, SUSARs throughout the study.","definition_or_measurement_approach":"Determination of MTD by observing incidence of specified toxicities across cohorts; rates of CRS, neurological toxicity, macrophage activation, graft-versus-recipient disease, grade 3-4 toxicities refractory to standard treatment, infusion reactions, SAEs and SUSARs will be recorded and used to define MTD."}
• {"endpoint_text":"- Safety variables: Tumour lysis syndrome.","definition_or_measurement_approach":"Occurrence and rate of tumour lysis syndrome events post-administration."}

Secondary endpoints

• {"endpoint_text":"- Determine cytopenias developed during the first 90 days or prolonged","definition_or_measurement_approach":"Assessment and recording of cytopenias occurring within first 90 days post-treatment or those that are prolonged."}
• {"endpoint_text":"- Duration of response in responder patients","definition_or_measurement_approach":"Time from documented response to disease progression or last follow-up."}
• {"endpoint_text":"- Overall response rate","definition_or_measurement_approach":"Proportion of patients achieving predefined response criteria."}
• {"endpoint_text":"- Time to complete remission","definition_or_measurement_approach":"Time from treatment to achievement of complete remission."}
• {"endpoint_text":"- Time to best response","definition_or_measurement_approach":"Time from treatment to the best observed response."}
• {"endpoint_text":"- Rate of bone marrow-negative EMR","definition_or_measurement_approach":"Proportion of patients with bone marrow-negative extramedullary response (as defined in protocol)."}
• {"endpoint_text":"- Extramedullary disease response rate","definition_or_measurement_approach":"Proportion of patients with response in extramedullary disease sites."}
• {"endpoint_text":"- Progression-free survival","definition_or_measurement_approach":"Time from treatment to disease progression or death."}
• {"endpoint_text":"- HUVR-CARTemis-1 administration and disease progression or death","definition_or_measurement_approach":"Assessment of temporal relationship between administration and subsequent progression or death events."}
• {"endpoint_text":"- Overall survival and patient death","definition_or_measurement_approach":"Time from treatment to death from any cause; overall survival rates."}
• {"endpoint_text":"- Persistence of HUVR-CARTemis-1 in peripheral blood and marrow","definition_or_measurement_approach":"Measurement of presence and persistence of CAR-T cells in peripheral blood and bone marrow over time."}
• {"endpoint_text":"- Evaluation of the biological characteristics of HUVR-CARTemis-1","definition_or_measurement_approach":"Laboratory analyses characterising generated HUVR-CARTemis-1 cells (phenotype, functionality, etc.)."}
• {"endpoint_text":"- BCMA expression","definition_or_measurement_approach":"Assessment of BCMA expression on myeloma cells (methodology as per protocol)."}
• {"endpoint_text":"- Levels of soluble BCMA","definition_or_measurement_approach":"Measurement of soluble BCMA levels in patient samples."}

Spain

Earliest CTIS Part Ii Submission Date

11-09-2023

Latest Decision Or Authorization Date

06-05-2024

Processing Time Days

238

Number Of Sites

5

Number Of Participants

25

Primary sponsor

Full Name

Fundacion Publica Andaluza para la Gestion de la Investigacion en Salud de Sevilla (FISEVI)

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain