First in Human Study of the Infusion of ARI0003 Cells in Relapsed/Refractory to Treatment B-cell Aggressive Lymphoma

Refractory Non-Hodgkin Lymphoma Clinical Trial

— CARTD-BG-1  

Official title:

First in Human, Pilot, Open-label, Prospective, Multicentre, Non-randomised Clinical Trial to Evaluate the Safety and Efficacy of ARI0003 (CART CD19/ CD269 Cells) in Patients With Relapsed/Refractory B-cell Aggressive Lymphoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06097455
• Other study ID #: CARTD-BG-1
• Secondary ID: 2023-5072-13-97-
• Status: Not yet recruiting
• Phase: Early Phase 1
• Start date: January 15, 2024
• Est. completion date: January 15, 2027

Study information

• Verified date: October 2023
• Source: Fundacion Clinic per a la Recerca Biomédica
• Contact: Julio Delgado, MD PhD
• Phone: +34932275400
• Email: jdelgado[@]clinic.cat
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

ths study consist in testing a CAR T therapy (ARI0003 cells (antiCD19 and antiBCMA) in patients suffering relapsed NHL (that means that symptoms of NHL reappeared ) or refractory (that means that they did not respond to other treatments). This is a first in human study.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 40
• Est. completion date: January 15, 2027
• Est. primary completion date: April 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 1. Diagnosis of CD19+ or CD269+ relapsed/refractory (R/R) aggressive B-cell lymphoma

in one of the following circumstances:

• Burkitt's lymphoma;
• Histology not covered by approved CART19-cell products (plasmablastic lymphoma, primary effusion lymphoma, intravascular lymphoma, transformed lymphoma from marginal zone lymphoma or chronic lymphocytic leukaemia, primary cutaneous DLBCL, T-cell rich DLBCL, high-grade B-cell lymphoma, grey zone lymphoma or grade 3b follicular lymphoma); or
• Aggressive B-cell lymphoma that is refractory or relapsing after treatment with CART19-cell therapy.

2. Age older than 18 years. 3. ECOG performance status of 0-2. 4. Estimated life expectancy of at least 3 months. 5. Adequate venous access and absence of contraindications for lymphapheresis. 6. Signature of informed consent. 7. In patients who have received any anti-CD19 or anti-CD269 therapy (e.g. tisagenlecleucel, axicabtagene autoleucel, tafasitamab, loncastuximab, belantamab mafodotin, idecabtagene vicleucel, etc.), a centralised tumour sample confirming the expression of at least one of the antigens (either CD19 or CD269) will be needed at study inclusion

Exclusion Criteria:

• 1. Any experimental or non-commercialized therapy in the previous 4 weeks. 2. 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.

3. Active immunosuppressive therapy except for prednisone 10 mg/day (or equivalent).

4. Active infection requiring systemic medical therapy. 5. Active HBV or HCV infection. 6. Positive serology for HIV. 7. Any concomitant and uncontrolled medical disease. 8. Severe organic impairment defined by cardiac ejection fraction <40%, DLCO <40%, GFR <30 ml/min or bilirubin >3 times the upper limit of normality (unless due to Gilbert's syndrome).

9. Lactating or pregnant women. 10. Men or women of childbearing potential unable or unwilling to use highly efficient contraceptive measures from the beginning until the end of the study.

11. CNS disease in the form of a macroscopic solid lesion in the encephalon or spinal cord (isolated meningeal disease is allowed

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin
• Refractory Non-Hodgkin Lymphoma
• Relapsed Non-Hodgkin Lymphoma

Intervention

Genetic:
• ARI0003
Treatment with ARI0003 cells

Locations

Country	Name	City	State
Spain	Hospital Clínic Barcelona	Barcelona
Spain	H. Ramon y Cajal	Madrid
Spain	H.U. Virgen de la Arrixaca	Murcia
Spain	Hospital Central de Asturias	Oviedo
Spain	Hospital Son Espases	Palma De Mallorca
Spain	H. Clínico de Salamanca	Salamanca
Spain	CHU Santiago de Compostela	Santiago De Compostela	A Coruña

Sponsors (1)

Lead Sponsor	Collaborator
Fundacion Clinic per a la Recerca Biomédica

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of > grade 3 CRS and/or ICANS	Rate of patients who develop grade > 3 cytokine release syndrome (CRS) and/or grade > 3 immune cell associated neurotoxicity syndrome (ICANS) according to the criteria and grading defined in the international consensus document of the American Society for Transplantation and Cellular Therapy (ASTCT criteria). ASTCT score can be between 1 and 4 (being 1 the minimum value and 4 the maximum) and where higher score means worse outcome.	in the first 30 days after ARI0003 administration
Primary	ORR	Overall response rate (ORR) according to Lugano criteria (best response within 3 months post ARI0003 infusion	within 3 months post ARI0003 infusion
Secondary	Procedure-related mortality (PRM)	Procedure-related mortality (PRM), defined as any death not directly cause by the lymphoma that is related with the procedure. For the estimation of PRM, disease relapse will be considered as a competing event	through study completion, an average of 24 months
Secondary	Toxicity: incidence of AE	Toxicity defined as the incidence of grade >3 adverse events (AEs) as per CTCAE version 5.0. The following AEs will be considered AEs of special interest (AESI): CRS, ICANS, macrophagic activation syndrome (MAS), tumour lysis syndrome (TLS), prolonged cytopenia (beyond 6 months), infections and second primary malignancies	at 3 and 12 months
Secondary	Complete response rate	Complete response rate	at 3 months
Secondary	Duration of response,	Duration of response, calculated from the time of first disease evaluation (3 months);	from month 3 to study completion, an average of 24 months
Secondary	Progression-free survival	Progression-free survival, calculated from ARI-0003 cell infusion	through study completion, an average of 24 months
Secondary	Overall survival	Overall survival, calculated from ARI-0003 cell infusion	through study completion, an average of 24 months