Clinical trial NCT03144583: Pilot Study on the Infusion of ARI-0001 Cells in Patients With CD19+ Leukemia or Lymphoma Refractory to Therapy
Official title: Pilot Study on the Infusion of Differentiated Autologous T-cells From Peripheral Blood, Expanded and Transduced With a Lentivirus to Express a Chimeric Antigen Receptor With Anti-CD19 Specificity Conjugated With the Co-stimulatory Regions 4-1BB and CD3z in Patients With CD19+ Leukemia or Lymphoma Refractory to Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Lymphoma
Keywords: CART19
Lead sponsor: Institut d'Investigacions Biomèdiques August Pi i Sunyer
Sponsor class: OTHER
Collaborators: name: Instituto de Salud Carlos III
First posted: 2017-05-09
Enrollment: 50
Sex: ALL
Minimum age (years): 2
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.


Eligibility criteria: Inclusion Criteria:

* 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).

Exclusion Criteria:

* 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.
* Central nervous system involvement (CNS-3) at inclusion. Inclusion will be permitted with patients with a lower grade (CNS-2) or with CNS-3 who have responded to intrathecal chemotherapy.
* 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.

Primary outcomes:
measure: Procedure-related mortality (PRM)
timeFrame: Year 1
measure: Procedure-related mortality (PRM)
timeFrame: Year 3
measure: Assessment of toxicity
timeFrame: Month 3
measure: Assessment of toxicity
timeFrame: Year 1
Secondary outcomes:
measure: Response rate (overall and complete)
timeFrame: Month 3 and Year 1
measure: Progression-free survival
timeFrame: Year 2 after procedure
measure: Overall survival (OS) at 2 years
timeFrame: 3 years
measure: In vivo survival of ARI-0001 cells in peripheral blood, bone marrow and cerebrospinal fluid
timeFrame: months 1,2,3,4,5,6
measure: In vivo survival of ARI-0001 cells in peripheral blood, bone marrow and cerebrospinal fluid
timeFrame: months 9,12,15,18,21,24
measure: Quality of life of included patients
timeFrame: Month 3, 6, 12
measure: Toxicity assessment
timeFrame: Month 3 and year 1
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: Hospital Clínic of Barcelona
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
Study officials:
affiliation: Hospital Clinic of Barcelona
name: Julio Delgado González, PhD MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.