Autologous genetically modified T lymphocytes transduced with lentivirus expressing CAR protein directed against BCMA for Primary plasma cell leukaemia

Inclusion criteria

• {"criterion_text":"- Patients between 18 and 75 years old diagnosed with newly diagnosed primary plasma cell leukemia (the presence of 5% or more circulating plasma cells in peripheral blood smears in patients otherwise diagnosed with symptomatic multiple myeloma), according to International Myeloma Working Group (IMWG). In order to confirm this inclusion criteria, two peripheral blood slides of the diagnostic will be sent to the coordinating team at HCB. In the event that a diagnostic slide is unavailable, a document confirming the diagnostic results must be provided instead.\n- Disease measurable at diagnosis by monoclonal component in serum or urine, or by free light chains in serum according to the eligibility criteria for clinical trials of the \"International Myeloma Working Group\".\n- ECOG Performance Status from 0 to 1\n- Life expectancy greater than 3 months\n- Adequate venous access and absence of contraindications for lymphoapheresis\n- Patients who, after being informed, give their consent by signing the Informed Consent Document."}

Exclusion criteria

• {"criterion_text":"- No previous treatments, except for induction therapy for primary plasma cell leukemia.\n- Severe organ impairment that meets any of the following criteria: EF<40%, DLCO <40%, GFR <30 ml/min, bilirubin >3 times the upper limit of normality (unless due to Gilbert syndrome).\n- Previous diagnosis of symptomatic AL amyloidosis.\n- Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at the screening phase.\n- Women of childbearing potential, including those whose last menstrual cycle was in the year prior to screening, who are unable or unwilling to use highly effective contraceptive methods from the beginning of the study to completion of the study.\n- Men who are unable or unwilling to use highly effective contraceptive methods from the beginning of the study to completion of the study.\n- Contraindication to receive lymphodepletive chemotherapy.\n- Administration of any anti-BCMA therapy as part of induction\n- Not having achieved at least a minimal response with induction treatment (IMWG criteria)\n- Absolute lymphocyte count <0.1x109/L\n- Active immunosuppressive therapy except for prednisone 10 mg/day (or equivalent)\n- Any other concomitant neoplasia, unless it has been in complete remission for 3 years or longer, except for non-melanoma skin cancer or completely resected in situ carcinoma.\n- Active infection requiring treatment.\n- Active HIV, HBV, or HCV infection.\n- Uncontrolled medical illness."}

Primary endpoints

• {"endpoint_text":"- Primary efficacy endpoints: Overall response rate (ORR) during the first 3 months after the first infusion (at least partial response according to the International Myeloma Working Group criteria)","definition_or_measurement_approach":"Overall response rate (ORR) during the first 3 months after first infusion; response assessed according to International Myeloma Working Group (IMWG) criteria."}
• {"endpoint_text":"- Primary safety endpoint: Rate of patients who develop a cytokine release syndrome and/or neurological toxicity in the first 30 days after CARTBCMA administration, according to the criteria and grading defined in the international consensus document (Lee, Santomasso et al. 2019).","definition_or_measurement_approach":"Rate of patients developing cytokine release syndrome and/or neurological toxicity within 30 days after CARTBCMA administration, graded per the international consensus document (Lee, Santomasso et al. 2019)."}

Secondary endpoints

• {"endpoint_text":"- Duration of response calculated from the time of first disease evaluation (day +28 after infusion) for those patients who achieved at least partial response.","definition_or_measurement_approach":"Duration of response measured from first disease evaluation (day +28 after infusion) for responders."}
• {"endpoint_text":"- Response rates during the first year.","definition_or_measurement_approach":"Response rates assessed during the first year after infusion."}
• {"endpoint_text":"- Complete response rate (CR) at 3, 6, and 12 months after the first infusion.","definition_or_measurement_approach":"Complete response (CR) rates measured at 3, 6 and 12 months post-infusion."}
• {"endpoint_text":"- Overall response rate at 6, and 12 months after the first infusion.","definition_or_measurement_approach":"Overall response rate assessed at 6 and 12 months post-infusion."}
• {"endpoint_text":"- Time to complete response.","definition_or_measurement_approach":"Time from infusion to documented complete response."}
• {"endpoint_text":"- Time to best response.","definition_or_measurement_approach":"Time from infusion to the best documented response."}
• {"endpoint_text":"- MRD negative rate in bone marrow by flow cytometry at 3, 6 12 and 24 months.","definition_or_measurement_approach":"MRD negativity in bone marrow assessed by flow cytometry at 3, 6, 12 and 24 months."}
• {"endpoint_text":"- Response rate of extramedullary disease by PET-CT at 3 and 12 months.","definition_or_measurement_approach":"Extramedullary disease response assessed by PET-CT at 3 and 12 months."}
• {"endpoint_text":"- Progression-free survival, defined as the time between administration of ARI0002h and disease progression or death. Patients who are alive and in complete remission will be censored at the time of the last follow-up.","definition_or_measurement_approach":"PFS defined as time from ARI0002h administration to disease progression or death; censoring at last follow-up for alive patients in CR."}
• {"endpoint_text":"- Progression-free survival at 12 months after the first administration, defined as the time elapsed between the administration of ARI0002h and disease progression or death. Patients who are alive and in complete remission will be censored at the time of the last follow-up.","definition_or_measurement_approach":"PFS at 12 months measured as time from ARI0002h administration to progression or death; censoring as above."}
• {"endpoint_text":"- Overall survival (OS), defined as the time between infusion of ARI0002h and death of the patient from any cause. Living patients will be censored at the time of last follow-up.","definition_or_measurement_approach":"OS defined as time from infusion to death from any cause; living patients censored at last follow-up."}
• {"endpoint_text":"- Presence of infusion reactions, understood as the appearance of any of the following symptoms after the intravenous administration of CARTBCMA: cardiac events, chills, dyspnoea, fatigue, sudden hypertension, hypotension, nausea, pain, fever, rash or urticaria.","definition_or_measurement_approach":"Occurrence of listed infusion reaction symptoms following IV administration."}
• {"endpoint_text":"- Tumour lysis syndrome at any time after treatment administration.","definition_or_measurement_approach":"Occurrence of tumour lysis syndrome at any time post-treatment."}
• {"endpoint_text":"- Cytokine release syndrome. According to the criteria and grading defined in the international consensus document (Lee, Santomasso et al. 2019 ).","definition_or_measurement_approach":"CRS occurrence and grading per Lee, Santomasso et al. 2019 international consensus."}
• {"endpoint_text":"- Neurological toxicity (According to the criteria and grading defined in the international consensus document (Lee, Santomasso et al. 2019)).","definition_or_measurement_approach":"Neurological toxicity occurrence and grading per Lee, Santomasso et al. 2019."}
• {"endpoint_text":"- Presence of prolonged cytopenias, defined as a grade 4 decrease in peripheral blood neutrophil or platelet counts for more than 4 weeks after infusion.","definition_or_measurement_approach":"Prolonged cytopenias defined as grade 4 neutrophil or platelet decreases lasting >4 weeks post-infusion."}
• {"endpoint_text":"- Quality of life during the first two years after infusion according to the 2009 EuroQol Group EQ-5D-5L questionnaire.","definition_or_measurement_approach":"Quality of life assessed using EQ-5D-5L during the first two years after infusion."}

Spain

Earliest CTIS Part Ii Submission Date

11-02-2025

Latest Decision Or Authorization Date

13-10-2025

Processing Time Days

244

Number Of Sites

8

Number Of Participants

25

Primary sponsor

Full Name

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain

Third parties

• {"country":"","full_name":"This study is financed by the Carlos III Health Institute (Project ICI23/00012)","duties_or_roles":"Financing/Monetary support (Project ICI23/00012)","organisation_type":""}