Clinical trial NCT06830733: Study to Evaluate the Safety and Efficacy of ARI0002h, for the Initial Treatment of Patients With Primary Plasma Cell Leukaemia
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Leukemia, Plasma Cell
Lead sponsor: Fundacion Clinic per a la Recerca Biomédica
Sponsor class: OTHER
First posted: 2025-02-17
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Overall response rate (ORR)
timeFrame: 3 months after the first infusion
measure: Rate of patients who develop cytokine release syndrome and/or neurological toxicity
timeFrame: 30 days after CARTBCMA administration
Secondary outcomes:
measure: Duration of response
timeFrame: From day 28 after infusion to study completion, an average of 24 months
measure: Response rates
timeFrame: During the first year after administration
measure: Complete response rate
timeFrame: at 3, 6, and 12 months after the first infusion
measure: Overall response rate
timeFrame: at 6, and 12 months after the first infusion
measure: Time to complete response
timeFrame: through study completion, an average of 24 months
measure: Time to best response
timeFrame: through study completion, an average of 24 months
measure: MRD negative rate in bone marrow
timeFrame: at 3, 6 12 and 24 months
measure: Response rate of extramedullary disease
timeFrame: at 3, 6 and 12 months.
measure: Progression-free survival
timeFrame: through study completion, an average of 24 months
measure: Progression-free survival at 12 months after the first administration
timeFrame: 12 months
measure: Overall survival
timeFrame: through study completion, an average of 24 months
measure: Presence of infusion reactions
timeFrame: through study completion, an average of 24 months
measure: Tumour lysis syndrome
timeFrame: through study completion, an average of 24 months
measure: Cytokine release syndrome
timeFrame: through study completion, an average of 24 months
measure: Neurological toxicity
timeFrame: through study completion, an average of 24 months
measure: Presence of prolonged cytopenias
timeFrame: between 4 weeks after infusion and study completion
measure: Quality of life of patients
timeFrame: during the first year after infusion
Other outcomes:
Locations:
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
state: Cantabria
city: Pamplona
country: Spain
facility: Clínica Universitaria de Navarra
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Clinic Barcelona
city: Madrid
country: Spain
facility: Clínica Universitaria de Navarra
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Murcia
country: Spain
facility: Hospital Universitario Virgen de la Arrixaca
city: Salamanca
country: Spain
facility: Complejo Asistencial Universitario de Salamanca
Study officials:
References: