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

Lymphoma Clinical Trial

— CART19-BE-01  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03144583
• Other study ID #: CART19-BE-01
• Status: Completed
• Phase: Phase 1
• Start date: June 15, 2017
• Est. completion date: September 13, 2022

Study information

• Verified date: August 2023
• Source: Institut d'Investigacions Biomèdiques August Pi i Sunyer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: September 13, 2022
• Est. primary completion date: September 13, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Leukemia
• Lymphoma

Intervention

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

Locations

Country	Name	City	State
Spain	Hospital Clínic of Barcelona	Barcelona
Spain	Hospital Sant Joan de Deu	Barcelona

Sponsors (2)

Lead Sponsor	Collaborator
Sara V. Latorre	Instituto de Salud Carlos III

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	Assessment of toxicity	number of adverse events grade III-IV using CTC (common toxicity criteria)	Month 3
Primary	Assessment of toxicity	number of adverse events grade III-IV using CTC (common toxicity criteria)	Year 1
Secondary	Response rate (overall and complete)	Defined differently for each disease: On chronic lymphoid and acute lymphocytic leukemia, the usual criteria NCCN and IWCLL will be used.; On non-Hodgkin's lymphoma, the Lugano criteria will be used-; On patients with leukemia will be quantified the persistence of minimal residual disease, in bone marrow and peripheral blood, using multiparametric cytometry and new generation sequencing techniques.	Month 3 and Year 1
Secondary	Progression-free survival	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	Year 2 after procedure
Secondary	Overall survival (OS) at 2 years	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.	3 years
Secondary	In vivo survival of ARI-0001 cells in peripheral blood, bone marrow and cerebrospinal fluid	Determined monthly during the first 6 months by flow cytometry and quantitative transgene PCR.	months 1,2,3,4,5,6
Secondary	In vivo survival of ARI-0001 cells in peripheral blood, bone marrow and cerebrospinal fluid	Determined quarterly from month 6 until the 2 years after infusion, by flow cytometry and quantitative transgene PCR.	months 9,12,15,18,21,24
Secondary	Quality of life of included patients	Evaluated by a questionnaire completed by patients or their legal guardians	Month 3, 6, 12
Secondary	Toxicity assessment	defined as number of adverse events of any type occurring throughout the study using the common toxicity criteria	Month 3 and year 1