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

Phase 2Not Yet RecruitingNCT06830733

Fundacion Clinic per a la Recerca Biomédica25 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Leukemia, Plasma Cell

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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). 2. 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". 3. ECOG Performance Status from 0 to 2 4. Life expectancy greater than 3 months. 5. Adequate venous access and absence of contraindications for lymphoapheresis. 6. Patients who, after being informed, give their consent by signing the Informed Consent Document. 7. Up to two cycles of previous treatment for symptomatic control will be allowed before inclusion. Exclusion Criteria: 1. No previous treatments, except for induction therapy for primary plasma cell leukemia. 2. Administration of any anti-BCMA therapy as part of induction 3. Not having achieved at least a minimal response with induction treatment (IMWG criteria) 4. Absolute lymphocyte count \<0.1x109/L 5. Active immunosuppressive therapy except for prednisone 10 mg/day (or equivalent). 6. 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. 7. Active infection requiring treatment. 8. Active HIV, HBV, or HCV infection. 9. Uncontrolled medical illness 10. 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) 11. Previous diagnosis of symptomatic AL amyloidosis, 12. Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test at the screening phase. 13. 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. 14. Men who are unable or unwilling to use highly effective contraceptive methods\* from the beginning of the study to completion of the study. 15. Contraindication to receive lymphodepletive chemotherapy.

Locations (7)

Hospital Marqués de Valdecilla

Santander, Cantabria, Spain

Clínica Universitaria de Navarra

Madrid, Madrid, Spain

Hospital 12 de Octubre

Madrid, Madrid, Spain

Hospital Universitario Virgen de la Arrixaca

Murcia, Murcia, Spain

Clínica Universitaria de Navarra

Pamplona, Navarre, Spain

Complejo Asistencial Universitario de Salamanca

Salamanca, Salamanca, Spain

Hospital Clinic Barcelona

Barcelona, Spain

Outcomes

Primary Outcomes

Overall response rate (ORR)

Overall response rate (ORR) during the initial 3 months after the first infusion (at least presenting a partial response according to the International Myeloma Working Group criteria).

Time frame: 3 months after the first infusion

Rate of patients who develop cytokine release syndrome and/or neurological toxicity

Rate of patients who develop 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

Time frame: 30 days after CARTBCMA administration

Secondary Outcomes

Duration of response

Duration of response calculated from the time of first disease evaluation

Time frame: From day 28 after infusion to study completion, an average of 24 months

Response rates

Time frame: During the first year after administration

Complete response rate

Time frame: at 3, 6, and 12 months after the first infusion

Overall response rate

Time frame: at 6, and 12 months after the first infusion

Time to complete response

Time frame: through study completion, an average of 24 months

Time to best response

Time frame: through study completion, an average of 24 months

MRD negative rate in bone marrow

MRD negative rate in bone marrow by flow cytometry

Time frame: at 3, 6 12 and 24 months

Response rate of extramedullary disease

Response rate of extramedullary disease by PET-CT

Time frame: at 3, 6 and 12 months.

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.

Time frame: through study completion, an average of 24 months

Progression-free survival at 12 months after the first administration

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.

Time frame: 12 months

Overall survival

Overall survival, 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.

Time frame: through study completion, an average of 24 months

Presence of infusion reactions

Presence of infusion reactions, understood as the appearance of any of the following symptoms after the intravenous administration of CARTBCMA: cardiac events, chills, dyspnea, fatigue, sudden hypertension, hypotension, nausea, pain, fever, rash or urticaria.

Time frame: through study completion, an average of 24 months

Tumour lysis syndrome

Time frame: through study completion, an average of 24 months

Cytokine release syndrome

Cytokine release syndrome. According to the criteria and grading defined in the international consensus document

Time frame: through study completion, an average of 24 months

Neurological toxicity

Neurological toxicity according to the criteria and grading defined in the international consensus document (Lee, Santomasso et al. 2019)

Time frame: through study completion, an average of 24 months

Presence of prolonged cytopenias

Presence of prolonged cytopenias, defined as a grade 4 decrease in peripheral blood neutrophil or platelet counts for more than 4 weeks after infusion.

Time frame: between 4 weeks after infusion and study completion

Quality of life of patients

Quality of life during the first year after infusion according to the Quality of life questionnaire 2008 EuroQol Group EQ-5D

Time frame: during the first year after infusion

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

Overview

Conditions

Interventions

Eligibility

Locations (7)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts