Clinical trial for the use of a humanized CART directed against BCMA (ARI0002h) in patients with newly diagnosed primary plasma cell leukemia.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

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

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

30 Apr 2025 → ongoing

Decision date (initial)

2025-03-10

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

This study is financed by the Carlos III Health Institute (Project ICI23/00012)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

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.

Secondary objectives 6

1. Evaluating the efficacy of ARI0002h
2. Assessing the duration of response after administration of ARI0002h
3. Evaluating the overall survival after the administration of ARI0002h
4. Evaluating the persistence of ARI0002h cells in peripheral blood after their administration
5. Evaluating the effect of treatment with ARI0002h on the quality of life of patient during the first year
6. Assessing adverse events occurring at 3 months and 1 year

Conditions and MedDRA coding

Plasma cell leukaemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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). 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.
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 1
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.

Exclusion criteria 15

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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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)
2. 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).

Secondary endpoints 17

1. Duration of response calculated from the time of first disease evaluation (day +28 after infusion) for those patients who achieved at least partial response.
2. Response rates during the first year.
3. Complete response rate (CR) at 3, 6, and 12 months after the first infusion.
4. Overall response rate at 6, and 12 months after the first infusion.
5. Time to complete response.
6. Time to best response.
7. MRD negative rate in bone marrow by flow cytometry at 3, 6 12 and 24 months.
8. Response rate of extramedullary disease by PET-CT at 3 and 12 months.
9. 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.
10. 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.
11. 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.
12. 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.
13. Tumour lysis syndrome at any time after treatment administration.
14. Cytokine release syndrome. According to the criteria and grading defined in the international consensus document (Lee, Santomasso et al. 2019 ).
15. Neurological toxicity (According to the criteria and grading defined in the international consensus document (Lee, Santomasso et al. 2019)).
16. Presence of prolonged cytopenias, defined as a grade 4 decrease in peripheral blood neutrophil or platelet counts for more than 4 weeks after infusion.
17. Quality of life during the first two years after infusion according to the 2009 EuroQol Group EQ-5D-5L questionnaire.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

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

Sponsor organisation

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

Address

Calle Rosellon 149-153

City

Barcelona

Postcode

08036

Country

Spain

Scientific contact point

Organisation

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

Contact name

Clinical Trials Unit

Public contact point

Organisation

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

Contact name

Clinical Trials Unit

Locations

1 EU/EEA country · 7 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications