- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03144583
Pilot Study on the Infusion of ARI-0001 Cells in Patients With CD19+ Leukemia or Lymphoma Refractory to Therapy (CART19-BE-01)
August 25, 2023 updated by: Sara V. Latorre
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
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.
Study Overview
Status
Completed
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
50
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Barcelona, Spain, 08036
- Hospital Clinic of Barcelona
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Barcelona, Spain, 08950
- Hospital Sant Joan de Déu
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
2 years to 80 years (Child, Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Adult differentiated autologous T-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.
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.
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After pretreatment, adult differentiated autologous T-cells with a chimeric antigen receptor with anti-CD19 specificity will be transfused.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Procedure-related mortality (PRM)
Time Frame: Year 1
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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.
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Year 1
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Procedure-related mortality (PRM)
Time Frame: Year 3
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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.
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Year 3
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Assessment of toxicity
Time Frame: Month 3
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number of adverse events grade III-IV using CTC (common toxicity criteria)
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Month 3
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Assessment of toxicity
Time Frame: Year 1
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number of adverse events grade III-IV using CTC (common toxicity criteria)
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Year 1
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Response rate (overall and complete)
Time Frame: Month 3 and Year 1
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Defined differently for each disease:
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Month 3 and Year 1
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Progression-free survival
Time Frame: Year 2 after procedure
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Time lag between infusion of ARI-0001 and the progression of disease or death.
Patients alive and in complete remission will be censored at the last follow-up
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Year 2 after procedure
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Overall survival (OS) at 2 years
Time Frame: 3 years
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Time lag between the infusion of ARI-0001 and the death of the patient from any cause.
Living patients will be censored at the the last follow-up.
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3 years
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In vivo survival of ARI-0001 cells in peripheral blood, bone marrow and cerebrospinal fluid
Time Frame: months 1,2,3,4,5,6
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Determined monthly during the first 6 months by flow cytometry and quantitative transgene PCR.
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months 1,2,3,4,5,6
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In vivo survival of ARI-0001 cells in peripheral blood, bone marrow and cerebrospinal fluid
Time Frame: months 9,12,15,18,21,24
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Determined quarterly from month 6 until the 2 years after infusion, by flow cytometry and quantitative transgene PCR.
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months 9,12,15,18,21,24
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Quality of life of included patients
Time Frame: Month 3, 6, 12
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Evaluated by a questionnaire completed by patients or their legal guardians
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Month 3, 6, 12
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Toxicity assessment
Time Frame: Month 3 and year 1
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defined as number of adverse events of any type occurring throughout the study using the common toxicity criteria
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Month 3 and year 1
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Investigators
- Principal Investigator: Julio Delgado González, PhD MD, Hospital Clinic of Barcelona
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
June 15, 2017
Primary Completion (Actual)
September 13, 2022
Study Completion (Actual)
September 13, 2022
Study Registration Dates
First Submitted
April 26, 2017
First Submitted That Met QC Criteria
May 4, 2017
First Posted (Actual)
May 9, 2017
Study Record Updates
Last Update Posted (Actual)
August 28, 2023
Last Update Submitted That Met QC Criteria
August 25, 2023
Last Verified
August 1, 2023
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CART19-BE-01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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