VARNIMCABTAGENE AUTOLEUCEL for Acute lymphoblastic leukemia

Inclusion criteria

• {"criterion_text":"- Diagnoses of CD19+ acute lymphoid leukemia, with a life expectancy of less than 2 years that meet the following conditions: Relapsed/refractory not candidate for transplantation (due to associated diseases or absence of donor) or in allogenic post-transplant relapse."}
• {"criterion_text":"- Measurable disease understood as the presence of measurable residual disease by flow cytometry in bone marrow or peripheral blood"}
• {"criterion_text":"- Age less than 70 years (from 18 to 70)"}
• {"criterion_text":"- ECOG functional status from 0 to 2"}
• {"criterion_text":"- Life expectancy of at least 3 months."}
• {"criterion_text":"- Adequate venous access to perform a lymphapheresis. Absence of contraindications for it"}
• {"criterion_text":"- Signature of informed consent"}

Exclusion criteria

• {"criterion_text":"- Treatment with any experimental or non-marketed substance within four weeks prior to recruitment, or actively participating in another therapeutic trial"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Positive serology for hepatitis C, defined as a positive test for anti-VHC antibodies confirmed by RIBA"}
• {"criterion_text":"- Concurrent uncontrolled medical illnesses including cardiac, renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological or psychiatric diseases that in the opinion of the investigator are potential risk factors to the patient"}
• {"criterion_text":"- Severe organ involvement, defined as cardiac ejection fraction <40%; DLCO <40%; calculated glomerular filtrate <30 ml/min; or bilirubin > 3 times the upper limit of normality (unless Gilbert syndrome)"}
• {"criterion_text":"- Pregnant or lactating women. Woman of childbearing potential should have a negative pregnancy test in the screening phase."}
• {"criterion_text":"- Women of childbearing potential, 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 completion of the study."}
• {"criterion_text":"- Men who cannot or do not wish to use highly effective contraceptive methods* from the beginning of the study until the end of the study"}
• {"criterion_text":"- Previous treatment with CART therapy (commercial or experimental)"}
• {"criterion_text":"- Diagnosis of another neoplasm, past or present. Patients may be included in complete remission for more than 3 years, or have a history of non-melanoma skin cancer or in-situ carcinoma resected completely."}
• {"criterion_text":"- Relief of central nervous system (CNS-3) at the time of inclusion. Inclusion will be permitted in patients with a lower grade (CNS-2) or CNS-3 who have responded to intrathecal chemotherapy"}
• {"criterion_text":"- Isolated extramedullary involvement (i.e. in the absence of minimal residual disease in peripheral blood, bone marrow, or cerebrospinal fluid)"}
• {"criterion_text":"- Early relapse after transplantation (less than 3 months for mononuclear cell apheresis, less than 6 months for infusion of ARI-0001)"}
• {"criterion_text":"- Active immunosuppressive treatment for graft-versus-host disease and other diseases. The use of corticosteroids to control leukaemia at the time of inclusion should be limited as much as possible and should be discontinued prior to infusion of ARI-0001 cells."}
• {"criterion_text":"- Active infection requiring systemic medical treatment such as chronic kidney infection, chronic lung infection or tuberculosis."}
• {"criterion_text":"- HIV infection"}

Primary endpoints

• {"endpoint_text":"- Response rate with measurable residual disease negative by multiparametric flow cytometry 28 days after infusion of ARI-0001 cells.","definition_or_measurement_approach":"Measured as measurable residual disease negative by multiparametric flow cytometry at 28 days after infusion of ARI-0001 cells."}

Secondary endpoints

• {"endpoint_text":"- Duration of response","definition_or_measurement_approach":"Duration of response as recorded from response assessment; specific assessment methods not further detailed in the record."}
• {"endpoint_text":"- Best response during the first 3 months of follow-up after administration of the first fractioned dose of ARI-0001","definition_or_measurement_approach":"Best response assessed during the first 3 months after the first fractionated dose; measurement methods not further specified beyond response evaluations."}
• {"endpoint_text":"- Progression-free survival at 6 months and 1 year of the infusion and after the signature of informed consent.","definition_or_measurement_approach":"Progression-free survival assessed at 6 months and 1 year after infusion (and after consent signature); standard PFS definitions implied but not further specified."}
• {"endpoint_text":"- Overall Survival (OS) at 1 year of the infusion and after the informed consent form signature","definition_or_measurement_approach":"Overall survival at 1 year after infusion (and after consent); measured as time to death from any cause."}
• {"endpoint_text":"- Assessment of ARI-0001 cell toxicity considering special interest in the following adverse events: CRS (cytokine release syndrome), encephalopathy associated with CARs (ICANS) and cerebral edema. Mortality related to study procedures and adverse events grade 3-4 will be evaluated at month 3 and year 1. Intensity will be assessed using CTCAE version 5.0 scale. To evaluate CRS and neurotoxicity ASTCT criteria will be used.","definition_or_measurement_approach":"Adverse events graded using CTCAE v5.0; CRS and neurotoxicity evaluated using ASTCT criteria; mortality and grade 3-4 AEs evaluated at month 3 and year 1."}
• {"endpoint_text":"- In vivo survival of ARI-0001 cells in peripheral blood, bone narrow and cerebrospinal fluid, to be determined by flow cytometry and quantitative transgene PCR with monthly frequency in the first 6 months and thereafter quarterly up to 2 years of infusion","definition_or_measurement_approach":"Measured by flow cytometry and quantitative transgene PCR monthly for first 6 months, then quarterly up to 2 years post-infusion."}

Spain

Earliest CTIS Part Ii Submission Date

17-04-2024

Latest Decision Or Authorization Date

13-05-2024

Processing Time Days

26

Number Of Sites

9

Number Of Participants

32

Primary sponsor

Full Name

Fundacio De Recerca Clinic Barcelona-Institut D’Investigacions Biomediques August Pi I Sunyer

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain

Third parties

• {"country":"","full_name":"Instituto de Salud Carlos III","duties_or_roles":"Source of monetary support","organisation_type":""}