Study to Evaluate the Safety and Efficacy of ARI0002h, for the Initial Treatment of Patients With Primary Plasma Cell Leukaemia

Официальное название

Phase II, Multicenter, Open-label, Prospective, Non-randomized Study to Evaluate the Safety and Efficacy of ARI0002h, a CAR-T Cell Against BCMA, for the Initial Treatment of Patients With Primary Plasma Cell Leukaemia

Обзор

Phase II, pilot, open-label, prospective, multicenter, non-randomized study to evaluate the safety and efficacy of ARI0002h (cesnicabtagene autoleucel) in 20 patients with newly diagnosed primary plasma cell leukemia (PCL). The study population is patients between 18 and 75 years of age with newly diagnosed primary plasma cell leukemia (pPCL), with a life expectancy of more than 3 months. The primary objective is to assess the safety and efficacy of CARTBCMA ARI0002h (cesnicabtagene autoleucel) after initial treatment to induce response in patients with newly diagnosed primary plasma cell leukaemia.

Вмешательства

• Генная терапия ARI0002h
  * Treatment with ARI0002h cells * Other names: CARTBCMA\_J22.9-h:CD8TM:4-1BB:CD3. Adult differentiated autologous T cells from peripheral blood, expanded and transduced with a lentivirus to express a chimeric antigen receptor with anti-BCMA (TNFRSF17) specificity conjugated to the 4-1BB co-stimulatory domain and the CD3z signalling domain that has been humanized.

Первичные конечные точки

• Overall response rate (ORR) [Срок оценки: 3 months after the first infusion]
• Rate of patients who develop cytokine release syndrome and/or neurological toxicity [Срок оценки: 30 days after CARTBCMA administration]

Вторичные конечные точки (12)

• Duration of response [Срок оценки: From day 28 after infusion to study completion, an average of 24 months]
• Response rates [Срок оценки: During the first year after administration]
• Complete response rate [Срок оценки: at 3, 6, and 12 months after the first infusion]
• Overall response rate [Срок оценки: at 6, and 12 months after the first infusion]
• Time to complete response [Срок оценки: through study completion, an average of 24 months]
• Time to best response [Срок оценки: through study completion, an average of 24 months]
• MRD negative rate in bone marrow [Срок оценки: at 3, 6 12 and 24 months]
• Response rate of extramedullary disease [Срок оценки: at 3, 6 and 12 months.]
• Progression-free survival [Срок оценки: through study completion, an average of 24 months]
• Progression-free survival at 12 months after the first administration [Срок оценки: 12 months]
• Overall survival [Срок оценки: through study completion, an average of 24 months]
• Presence of infusion reactions [Срок оценки: through study completion, an average of 24 months]

Критерии участия

Критерии включения

• 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).
• 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".
• ECOG Performance Status from 0 to 2
• Life expectancy greater than 3 months.
• Adequate venous access and absence of contraindications for lymphoapheresis.
• Patients who, after being informed, give their consent by signing the Informed Consent Document.
• Up to two cycles of previous treatment for symptomatic control will be allowed before inclusion.

Критерии исключения

• No previous treatments, except for induction therapy for primary plasma cell leukemia.
• Administration of any anti-BCMA therapy as part of induction
• Not having achieved at least a minimal response with induction treatment (IMWG criteria)
• Absolute lymphocyte count <0.1x109/L
• Active immunosuppressive therapy except for prednisone 10 mg/day (or equivalent).
• 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.
• Active infection requiring treatment.
• Active HIV, HBV, or HCV infection.
• Uncontrolled medical illness
• 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)
• Previous diagnosis of symptomatic AL amyloidosis,
• Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at the screening phase.
• 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.
• Men who are unable or unwilling to use highly effective contraceptive methods\* from the beginning of the study to completion of the study.
• Contraindication to receive lymphodepletive chemotherapy.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Испания · 7 центров

• Hospital Marqués de Valdecilla — Santander
• Clínica Universitaria de Navarra — Madrid
• Hospital 12 de Octubre — Madrid
• Hospital Universitario Virgen de la Arrixaca — Murcia
• Clínica Universitaria de Navarra — Pamplona
• Complejo Asistencial Universitario de Salamanca — Salamanca
• Hospital Clinic Barcelona — Barcelona

Идентификаторы

NCT: NCT06830733 · 2024-515053-21-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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