VARNIMCABTAGENE AUTOLEUCEL for Acute lymphoblastic leukemia

Inclusion criteria

• {"criterion_text":"- Age 0 to 18 years"}
• {"criterion_text":"- Diagnosis of relapsed /refractory CD19+ ALL defined as at least one of the following criteria: • First relapse if high-risk features. Definition of high risk 1st relapse will include at least one of the following: o any relapse before 6 months after completion of chemotherapy o high risk cytogenetics: t(4;11)(q21; q23) /AF4:: KMT2A or t (1;19) (q23; p13) / TCF3/PBX or t(17;19) (q22;p13)/ TCF3::HLF or hypodiploid (<44 chromosomes) or TP53 mutation and/ or TP53 deletion"}
• {"criterion_text":"- Disease burden defined as: • Morphologic relapse in bone marrow (≥5% blasts) or presence of leukemic blasts in an extramedullary site • MRD positivity (≥0.01%) by flow cytometry or PCR"}
• {"criterion_text":"- Subjects with the following features are NOT excluded: • Isolated extramedullary involvement • Down syndrome patients • CNS3 involvement if disease is stable and a thorough evaluation of risk/benefit assessment has been stablished by the principal investigator and the treating physician • Ph+ (BCR::ABL1) ALL if they are intolerant or have failed at least 1 TKI • Prior blinatumomab therapy provided blasts remain CD19+ >90% blasts at inclusion"}
• {"criterion_text":"- Performance status: Lansky (age <16 years) or Karnofsky (age ≥16 years) ≥ 50%"}
• {"criterion_text":"- Life expectancy >3 months"}
• {"criterion_text":"- Adequate venous access and no contraindications for lymphoapheresis"}
• {"criterion_text":"- Signature of informed consent (patient and/or legal guardian)"}

Exclusion criteria

• {"criterion_text":"- Any other concomitant neoplasia, unless it has been in complete remission for 3 years or longer"}
• {"criterion_text":"- Lactating or pregnant women"}
• {"criterion_text":"- Men or women of childbearing potential unable or unwilling to use highly efficient contraceptive measures during the study"}
• {"criterion_text":"- Active immunosuppressive therapy with the exception of hydrocortisone 12 mg/m2/day (or equivalent);"}
• {"criterion_text":"- Active acute or chronic graft versus host disease (GVHD) >grade 1"}
• {"criterion_text":"- Prior therapies: • CAR-T cell therapy • Donor lymphocytes infusion <28 days before enrollment • Immunosuppressive therapy (cyclosporine, mophetil mycophenolate and others) must be stopped <14 days before enrollment • Alentuzumab, thymoglobulin (ATG) < 3 months before enrollment"}
• {"criterion_text":"- Active infection that is uncontrolled or requiring systemic intravenous medical therapy;"}
• {"criterion_text":"- Any experimental or non-commercialized therapy in the previous 4 weeks"}
• {"criterion_text":"- Active HIV, HBV or HCV infection"}
• {"criterion_text":"- Any concomitant and uncontrolled medical or psychiatric disease that, under investigator consideration, would prevent the subject from participating in the study"}
• {"criterion_text":"- Severe organic impairment defined by cardiac ejection fraction <50%, pulmonary reserve defined as > Grade 1 dyspnea and pulse oxygenation <91% on room air, creatinine >1.5 times greater than the upper limit of normality (ULN) for sex and age or conjugated bilirubin >2 x ULN"}

Primary endpoints

• {"endpoint_text":"- Complete response rate (complete remission [CR] rate plus CR rate with incomplete haematological recovery [CRi]), with undetectable measurable residual disease by multiparameter flow cytometry within day +100 after the infusion of ARI-0001 cells. In patients with isolated extramedullary disease, response evaluation will be done through morphology and flow cytometry of the cerebrospinal fluid (CSF) and/or imaging tests (PET-CT or MRI)","definition_or_measurement_approach":"Complete response rate defined as CR + CRi with undetectable measurable residual disease by multiparameter flow cytometry within day +100 after infusion; for isolated extramedullary disease, evaluation by CSF morphology and flow cytometry and/or imaging (PET-CT or MRI)."}

Secondary endpoints

• {"endpoint_text":"- Key secondary endpoint: Event-free survival (EFS) at month 12","definition_or_measurement_approach":"Event-free survival at 12 months (time-to-event endpoint measured at month 12)."}
• {"endpoint_text":"- Duration of remission: defined as the time from achievement of CR or CRi (whichever occurs first) to relapse or death due to ALL","definition_or_measurement_approach":"Time from achievement of CR or CRi to relapse or death due to ALL."}
• {"endpoint_text":"- Relapse free survival (RFS) at 12 months","definition_or_measurement_approach":"Relapse-free survival measured at 12 months."}
• {"endpoint_text":"- Overall survival at 12 months","definition_or_measurement_approach":"Overall survival measured at 12 months."}
• {"endpoint_text":"- Transplant and disease-free survival at 6 and 12 months","definition_or_measurement_approach":"Transplant and disease-free survival measured at 6 and 12 months."}
• {"endpoint_text":"- In vivo survival of ARI-0001 cells in peripheral blood as determined by flow cytometry and by qPCR of the transgene weekly the first month, monthly in the first 6 months and then at 12 months.","definition_or_measurement_approach":"Kinetics assessed by flow cytometry and qPCR weekly in month 1, monthly through month 6, and at month 12."}
• {"endpoint_text":"- B-cell aplasia, measured by flow cytometry, weekly the first month, monthly in the first 6 months, every 3 months from month 6 to month 12 and every 6 months until end of study","definition_or_measurement_approach":"B-cell aplasia measured by flow cytometry with scheduled timepoints: weekly in month 1, monthly through month 6, every 3 months from month 6–12, then every 6 months until end of study."}
• {"endpoint_text":"- Toxicity, defined as adverse events of grade ≥3 according to common toxicity criteria (version 5.0). Adverse events of significant interest will be CRS, ICANS and cerebral ooedema, which will be graded according to the ASTCT classification (1). Procedure-related mortality will also be measured.","definition_or_measurement_approach":"Safety assessed by adverse events grade ≥3 per CTCAE v5.0; CRS, ICANS and cerebral oedema graded per ASTCT; procedure-related mortality recorded."}

Spain

Earliest CTIS Part Ii Submission Date

17-07-2024

Latest Decision Or Authorization Date

16-01-2026

Processing Time Days

548

Number Of Sites

5

Number Of Participants

33

Primary sponsor

Full Name

Fundacio Sant Joan De Deu

Organisation Type

Patient organisation/association

Country Of Registered Address

Spain