Clinical trial NCT06097455: First in Human Study of the Infusion of ARI0003 Cells in Relapsed/Refractory to Treatment B-cell Aggressive Lymphoma
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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: EARLY_PHASE1
Conditions: Refractory Non-Hodgkin Lymphoma
Relapsed Non-Hodgkin Lymphoma
Lead sponsor: Fundacion Clinic per a la Recerca Biomédica
Sponsor class: OTHER
First posted: 2023-10-24
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Rate of > grade 3 CRS and/or ICANS
timeFrame: in the first 30 days after ARI0003 administration
measure: ORR
timeFrame: within 3 months post ARI0003 infusion
Secondary outcomes:
measure: Procedure-related mortality (PRM)
timeFrame: through study completion, an average of 24 months
measure: Toxicity: incidence of AE
timeFrame: at 3 and 12 months
measure: Complete response rate
timeFrame: at 3 months
measure: Duration of response,
timeFrame: from month 3 to study completion, an average of 24 months
measure: Progression-free survival
timeFrame: through study completion, an average of 24 months
measure: Overall survival
timeFrame: through study completion, an average of 24 months
Other outcomes:
Locations:
city: Santiago De Compostela
country: Spain
facility: CHU Santiago de Compostela
state: A Coruña
city: Barcelona
country: Spain
facility: Hospital Clínic Barcelona
city: Madrid
country: Spain
facility: H. Ramon y Cajal
city: Murcia
country: Spain
facility: H.U. Virgen de la Arrixaca
city: Oviedo
country: Spain
facility: Hospital Central de Asturias
city: Palma De Mallorca
country: Spain
facility: Hospital Son Espases
city: Salamanca
country: Spain
facility: H. Clínico de Salamanca
Study officials:
References: