Pilot Study on the Infusion of ARI-0001 Cells in Patients With CD19+ Leukemia or Lymphoma Refractory to Therapy

NCT03144583 | Completed Phase 1 DMC

• 1 other identifier: CART19-BE-01
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

To assess the infusion of ARI-0001 cells (Adult differentiated autologous T-cells from peripheral blood, expanded and transduced with a lentivirus to express a chimeric antigen receptor with anti-CD19 specificity \[A3B1\] conjugated with the co-stimulatory regions 4-1BB and CD3z ) safety on patients with leukemia or lymphoma CD19+ resistant or refractory to treatment and with a prognosis of less than 2 years.

Conditions

Leukemia; Lymphoma

Keywords

CART19

Outcome Measures

Primary Outcomes (4)

• Procedure-related mortality (PRM)

  Any death not caused directly by leukemia / lymphoma. For the estimation of PRM, relapse or progression of the disease will be considered as a competitive event.

  Year 1

• Procedure-related mortality (PRM)

  Any death not caused directly by leukemia / lymphoma. For the estimation of PRM, relapse or progression of the disease will be considered as a competitive event.

  Year 3

• Assessment of toxicity

  number of adverse events grade III-IV using CTC (common toxicity criteria)

  Month 3

• Assessment of toxicity

  number of adverse events grade III-IV using CTC (common toxicity criteria)

  Year 1

Secondary Outcomes (7)

• Response rate (overall and complete)

  Month 3 and Year 1

• Progression-free survival

  Year 2 after procedure

• Overall survival (OS) at 2 years

  3 years

• In vivo survival of ARI-0001 cells in peripheral blood, bone marrow and cerebrospinal fluid

  months 1,2,3,4,5,6

• In vivo survival of ARI-0001 cells in peripheral blood, bone marrow and cerebrospinal fluid

  months 9,12,15,18,21,24

Study Arms (1)

Adult differentiated autologous T-cells

EXPERIMENTAL

Adult differentiated autologous T-cells from peripheral blood, expanded and transduced with a lentivirus to express a chimeric antigen receptor with anti-CD19 specificity (A3B1) conjugated with the co-stimulatory regions 4-1BB and CD3z. Such cells will be administered in a single infusion intravenously at a total ARI-0001 cell dose of 0.5-10 x 106 / kg body weight.

Biological: Adult differentiated autologous T-cells

Interventions

Adult differentiated autologous T-cells BIOLOGICAL

After pretreatment, adult differentiated autologous T-cells with a chimeric antigen receptor with anti-CD19 specificity will be transfused.

Adult differentiated autologous T-cells

Eligibility Criteria

• Age: 2 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of leukemia or CD19 + lymphoma, with a life expectancy less than 2 years that meet the following conditions:- Adult acute lymphoid leukemia in second or third response, not candidate for transplantation due to age, associated diseases or lack of donor, or in relapse post allogeneic transplant.- Pediatric acute lymphoid leukemia in second or third response, refractory or non-transplant candidate due to donor absence, or in relapse post allogeneic transplant, or with minimal residual residual disease (0.1% or greater) after two or more lines of treatment. - Symptomatic follicular lymphoma, which has received at least 2 treatment regimens (one of them including rituximab) and a progression-free interval of less than 2 years. Patients not candidates for transplantation or post-transplant relapse may be included.- Symptomatic chronic lymphocytic leukemia, which has received at least 2 treatment regimens (one of them including rituximab) and a progression-free survival of less than 2 years. Patients with a 17p deletion or TP53 mutation may be included after the first line of treatment. - Mantle cell lymphoma in the first relapse (or higher) when it is not a candidate for transplantation, or second post-transplant relapse (or higher). - Diffuse large cell lymphoma in first relapse (or higher) when it is not a candidate for transplantation, or second post-transplant relapse (or higher).
• Age greater than 2 years and less than 80.
• ECOG functional status from 0 to 2
• Life expectancy of at least 3 months.
• Appropriate venous access to perform an apheresis procedure. Absence of contraindications for it.
• Signature of informed consent (patient or legal guardian).

You may not qualify if:

• Treatment with any experimental or non-marketed substance within four weeks prior to recruitment, or actively participating in another therapeutic clinical trial.
• Diagnosis of another past or present neoplasm. Patients may be included in complete remission for more than 3 years, or with a history of non-melanoma skin cancer or completely resected in-situ carcinoma.
• Early relapse after allogeneic transplantation (less than 3 months for apheresis of mononuclear cells, less than 6 months for infusion of ARI-0001) or patients on active immunosuppressive therapy for graft-versus-host disease (corticosteroids or other systemic immunosuppressants ).
• Active infection requiring systemic medical treatment such as chronic kidney infection, chronic lung infection or tuberculosis.
• HIV infection.
• Concurrent and uncontrolled medical illnesses including cardiac, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological or psychiatric diseases which in the opinion of the researcher represent a risk to the patient.
• Positive serology for hepatitis B, defined as a positive test for HBsAg. In addition, if the patient is HBsAg negative but has anti-HBc antibodies it will be necessary to perform a DNA test of the hepatitis B virus, and if the result is positive the patient will be excluded.
• Positive serology for hepatitis C, defined as a positive test for anti-HCV antibodies confirmed by RIBA.
• Severe organ failure, defined as a cardiac ejection fraction \<40%; DLCO \<40%; calculated glomerular filtrate rate \<30 ml / min; Or bilirubin\> 3 times the upper limit of normal (unless it is due to CLL or Gilbert syndrome).
• Pregnant or lactating women. Women of childbearing potential should have a negative pregnancy test in the screening phase.
• Women of childbearing age, 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 start of the study to the end of the study.
• Men who are unable or unwilling to use highly effective contraceptive methods from the start of the study to the completion of the study.
• The need to take glucocorticoids in a chronic manner at doses higher than 10 mg / day of prednisone (or equivalent) or other chronic immunosuppressants. Hormonal contraceptives, intrauterine device, intrauterine systems of hormonal release, sexual abstinence, vasectomy of the couple or bilateral tubal occlusion.

Sponsors & Collaborators

• Sara V. Latorre: lead
• Instituto de Salud Carlos III: collaborator

Study Sites (2)

Hospital Clínic of Barcelona

Barcelona, 08036, Spain

Location

Hospital Sant Joan de Deu

Barcelona, 08950, Spain

Location

Related Publications (5)

• Bartolo-Ibars A, Aran A, Johansson AM, Ortiz-Maldonado V, Klein-Gonzalez N, Alonso-Saladrigues A, James E, Urbano-Ispizua A, Rives S, Delgado J, Gonzalez-Navarro EA, Kwok WW, Juan M. T-cell responses against CD19-targeted CAR T cells varnimcabtagene autoleucel (ARI-0001): implications for immune response and therapy outcomes. J Immunother Cancer. 2025 Sep 22;13(9):e010792. doi: 10.1136/jitc-2024-010792.

  PMID: 40987492 DERIVED

• Martinez-Cibrian N, Ortiz-Maldonado V, Espanol-Rego M, Alserawan L, Navarro S, Albiol N, Lozano M, Charry P, Magnano L, Rivero A, Correa JG, Mozas P, Cortes-Bullich A, Jimenez-Vicente C, Gine E, Montoro-Lorite M, Ramos C, Ayora P, Calderon H, Sanchez-Castanon M, Benitez-Ribas D, Mata-Molanes JJ, Rojas K, Setoain X, Rodriguez S, Murias A, Alcubilla P, Varea S, Olesti E, Bachiller M, Calvo-Orteu M, Sans-Pola C, Saez-Penataro J, de Larrea CF, Lopez-Guillermo A, Gonzalez-Navarro EA, Juan M, Delgado J. Efficacy and safety of the academic anti-CD19 chimeric antigen receptor T-cell product varnimcabtagene autoleucel for the treatment of relapsed/refractory follicular lymphoma. Hemasphere. 2025 Sep 11;9(9):e70166. doi: 10.1002/hem3.70166. eCollection 2025 Sep.

  PMID: 40951523 DERIVED

• Martinez-Cibrian N, Ortiz-Maldonado V, Espanol-Rego M, Blazquez A, Cid J, Lozano M, Magnano L, Gine E, Correa JG, Mozas P, Rodriguez-Lobato LG, Rivero A, Montoro-Lorite M, Ayora P, Navarro S, Alserawan L, Gonzalez-Navarro EA, Castella M, Sanchez-Castanon M, Cabezon R, Benitez-Ribas D, Setoain X, Rodriguez S, Brillembourg H, Varea S, Olesti E, Guillen E, Saez-Penataro J, de Larrea CF, Lopez-Guillermo A, Pascal M, Urbano-Ispizua A, Juan M, Delgado J. The academic point-of-care anti-CD19 chimeric antigen receptor T-cell product varnimcabtagene autoleucel (ARI-0001 cells) shows efficacy and safety in the treatment of relapsed/refractory B-cell non-Hodgkin lymphoma. Br J Haematol. 2024 Feb;204(2):525-533. doi: 10.1111/bjh.19170. Epub 2023 Oct 31.

  PMID: 37905734 DERIVED

• Ortiz-Maldonado V, Rives S, Castella M, Alonso-Saladrigues A, Benitez-Ribas D, Caballero-Banos M, Baumann T, Cid J, Garcia-Rey E, Llanos C, Torrebadell M, Villamor N, Gine E, Diaz-Beya M, Guardia L, Montoro M, Catala A, Faura A, Gonzalez EA, Espanol-Rego M, Klein-Gonzalez N, Alsina L, Castro P, Jordan I, Fernandez S, Ramos F, Sune G, Perpina U, Canals JM, Lozano M, Trias E, Scalise A, Varea S, Saez-Penataro J, Torres F, Calvo G, Esteve J, Urbano-Ispizua A, Juan M, Delgado J. CART19-BE-01: A Multicenter Trial of ARI-0001 Cell Therapy in Patients with CD19+ Relapsed/Refractory Malignancies. Mol Ther. 2021 Feb 3;29(2):636-644. doi: 10.1016/j.ymthe.2020.09.027. Epub 2020 Sep 20.

  PMID: 33010231 DERIVED

• Castella M, Caballero-Banos M, Ortiz-Maldonado V, Gonzalez-Navarro EA, Sune G, Antonana-Vidosola A, Boronat A, Marzal B, Millan L, Martin-Antonio B, Cid J, Lozano M, Garcia E, Tabera J, Trias E, Perpina U, Canals JM, Baumann T, Benitez-Ribas D, Campo E, Yague J, Urbano-Ispizua A, Rives S, Delgado J, Juan M. Point-Of-Care CAR T-Cell Production (ARI-0001) Using a Closed Semi-automatic Bioreactor: Experience From an Academic Phase I Clinical Trial. Front Immunol. 2020 Mar 20;11:482. doi: 10.3389/fimmu.2020.00482. eCollection 2020.

  PMID: 32528460 DERIVED

MeSH Terms

Conditions

Leukemia; Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Julio Delgado González, PhD MD

  Hospital Clinic of Barcelona

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Masking Details: Open label
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Research Manager

Study Record Dates

• First Submitted: April 26, 2017
• First Posted: May 9, 2017
• Study Start: June 15, 2017
• Primary Completion: September 13, 2022
• Study Completion: September 13, 2022
• Last Updated: August 28, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2)