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

Early Phase 1

Not yet recruiting

• Conditions: Refractory Non-Hodgkin Lymphoma; Relapsed Non-Hodgkin Lymphoma
• Interventions: Genetic: ARI0003

• Registration Number: NCT06097455
• Lead Sponsor: Fundacion Clinic per a la Recerca Biomédica

Brief 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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2023-10
• Study First Submitted: 2023-10-09
• Study First Submitted QC: 2023-10-18
• Study First Posted: 2023-10-24
• Last Update Submitted: 2023-10-24
• Last Update Posted: 2023-10-26
• Study Start: 2024-01-15
• Primary Completion: 2025-04-15
• Study Completion: 2027-01-15

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 40

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.

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

  3. 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).

  4. 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.

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ARI0003	ARI0003	ARI0003 will be administered intravenously under a split regime. A total dose between 0.5 and 5 x106 cell/Kg will be administered in 3 administrations (fractions):

Primary Outcome Measures

Name	Time	Method
Rate of > grade 3 CRS and/or ICANS	in the first 30 days after ARI0003 administration	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.
ORR	within 3 months post ARI0003 infusion	Overall response rate (ORR) according to Lugano criteria (best response within 3 months post ARI0003 infusion

Secondary Outcome Measures

Name	Time	Method
Procedure-related mortality (PRM)	through study completion, an average of 24 months	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
Complete response rate	at 3 months	Complete response rate
Progression-free survival	through study completion, an average of 24 months	Progression-free survival, calculated from ARI-0003 cell infusion
Overall survival	through study completion, an average of 24 months	Overall survival, calculated from ARI-0003 cell infusion
Toxicity: incidence of AE	at 3 and 12 months	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
Duration of response,	from month 3 to study completion, an average of 24 months	Duration of response, calculated from the time of first disease evaluation (3 months);

Trial Locations

Locations (7)

CHU Santiago de Compostela; 🇪🇸 Santiago De Compostela, A Coruña, Spain

Hospital Clínic Barcelona; 🇪🇸 Barcelona, Spain

H. Ramon y Cajal; 🇪🇸 Madrid, Spain

Hospital Son Espases; 🇪🇸 Palma De Mallorca, Spain

H.U. Virgen de la Arrixaca; 🇪🇸 Murcia, Spain

Hospital Central de Asturias; 🇪🇸 Oviedo, Spain

H. Clínico de Salamanca; 🇪🇸 Salamanca, Spain