Study to Evaluate the Safety and Efficacy of ARI0002h, for the Initial Treatment of Patients With Primary Plasma Cell Leukaemia (GEM-PLASMACAR)

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

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 Overview

• Status: Not yet recruiting
• Conditions: Leukemia, Plasma Cell
• Intervention / Treatment: Genetic: ARI0002h

• Study Type: Interventional
• Enrollment (Estimated): 25
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Maria Joyera; Phone Number: +34932775400; Email: joyera@recerca.clinic.cat
• Study Contact Backup: Name: Carlos Fernandez de Larrea, MD, PhD; Phone Number: +34932775400; Email: cfernan1@clinic.cat

Study Locations

• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic Barcelona
    • Contact: Carlos Fernandez de Larrea; Phone Number: +34932275400; Email: cfernan1@clinic.cat
  • Madrid, Spain, 28041
    • Hospital 12 de Octubre
    • Contact: Rafael Alonso; Phone Number: 913 90 80 00; Email: rafaelalberto.alonso@salud.madrid.org
  • Madrid, Spain, 28027
    • Clinica Universitaria de Navarra
    • Contact: Paula Rodríguez Otero; Phone Number: 913 53 19 20; Email: paurodriguez@unav.es
  • Murcia, Spain, 30120
    • Hospital Universitario Virgen de la Arrixaca
    • Contact: Valentín Cabañas; Phone Number: 968 36 95 00; Email: valentin.cabanas@gmail.com
  • Salamanca, Spain, 37007
    • Complejo Asistencial Universitario de Salamanca
    • Contact: María Victoria Mateos; Phone Number: 923 29 11 00; Email: mvmateos@usal.es
  • Cantabria
    • Santander, Cantabria, Spain, 39008
      • Hospital Marqués de Valdecilla
      • Contact: María Aranzazu Bermúdez Rodriguez; Phone Number: 942 20 25 20; Email: maranzazu.bermudez@scsalud.es
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria de Navarra
      • Contact: Paula Rodríguez Otero; Phone Number: 948 25 54 00; Email: paurodriguez@unav.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ARI0002h; ARI0002 will be administered intravenously in two doses. First dose will b e a fractionated infusion of three doses of the investigational medicinal product (day 0: 10% dose, day 3: 30% dose, day 7: 60% dose), and a second adminsitration as a single dose at 2 months after the first in those patients who have achieved at least a minimal response, have not presented PCL progression after the first infusion or serious complications after the first infusion.

Genetic: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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	30 days after CARTBCMA administration

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of response	Duration of response calculated from the time of first disease evaluation	From day 28 after infusion to study completion, an average of 24 months
Response rates	Response rates	During the first year after administration
Complete response rate	Complete response rate	at 3, 6, and 12 months after the first infusion
Overall response rate	Overall response rate	at 6, and 12 months after the first infusion
Time to complete response	Time to complete response	through study completion, an average of 24 months
Time to best response	Time to best response	through study completion, an average of 24 months
MRD negative rate in bone marrow	MRD negative rate in bone marrow by flow cytometry	at 3, 6 12 and 24 months
Response rate of extramedullary disease	Response rate of extramedullary disease by PET-CT	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.	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.	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.	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.	through study completion, an average of 24 months
Tumour lysis syndrome	Tumour lysis syndrome	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	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)	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.	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	during the first year after infusion

Collaborators and Investigators

• Sponsor: Fundacion Clinic per a la Recerca Biomédica

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: November 20, 2024
• First Submitted That Met QC Criteria: February 11, 2025
• First Posted (Actual): February 17, 2025

Study Record Updates

• Last Update Posted (Actual): April 25, 2025
• Last Update Submitted That Met QC Criteria: April 24, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Multiple Myeloma; Leukemia; Leukemia, Plasma Cell
• Other Study ID Numbers: 2024-515053-21-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No