LATE-R Trial. A Phase II, Single-Arm, Open-Label, Multicenter Study to Evaluate the Efficacy of Axicabtagene Ciloleucel in Patients With Late Relapse of Diffuse Large B-Cell Lymphoma
Single-arm, open-label, multicenter, phase II trial aiming to include approximately 45 patients over 24 months. Patients will receive axicabtagene ciloleucel infusion and will be followed up to 5 years. The total duration of the study is therefore of 7 years.
• Signed written Informed Consent Form
• Age \> 18 years
• Patient who understands and speaks one of the country official languages
• Histologically proven relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (B-NHL) of the following histology at relapse: diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL) and follicular lymphoma Grade 3B per WHO 2016 classification. Indolent B-NHL who transformed into aggressive B-NHL and were previously treated with R-CHOP-like after transformation are eligible. Primary mediastinal B-cell lymphoma are not eligible.
• Positron-emission tomography (PET)-positive disease
• Patients must have received adequate first-line therapy including at a minimum:
‣ An anti-CD20 monoclonal antibody (rituximab or obinutuzumab), and
⁃ CHOP or CHOP-like chemotherapy Note: CHOP-like chemotherapy corresponds to ACVBP, EPOCH, or COPADEM. Dose-reduced CHOP (i.e., miniCHOP) is excluded except for dose-reductions of vincristine due to peripheral neuropathy. Patients who have received additional drugs in combination with CHOP or CHOP-like regimen are eligible.
• Relapsed disease after first line chemo immunotherapy (full dose of R-CHOP or R-CHOP-like regimen), documented by PET-scan and biopsy:
• • Relapsed disease defined as complete remission to first-line therapy followed by biopsy-proven disease relapse after 12 months and up to 5 years from end of first-line therapy.
• Patients must meet CAR-T-eligible criteria as defined by:
‣ Patient deemed eligible for CAR T-cells therapy by the CAR-T physician
⁃ AND all the following criteria:
• ECOG performance status of 0, 1 or 2
∙ Adequate vascular access for leukapheresis procedure (either peripheral or central venous line)
∙ Absolute neutrophil count (ANC) ≥ 1 x 109/L
∙ Platelets ≥ 75 x 109/L
∙ Absolute lymphocyte count ≥ 0.1 x 109/L
∙ Creatinine clearance (CrCl) as estimated by Cockcroft Gault or MDRD ≥ 40 mL/min
∙ Serum alanine aminotransferase/aspartate aminotransferase (ALT/AST) ≤ 2.5xULN
∙ Total bilirubin \<1.5 mg/dL, except in patients with Gilbert's syndrome
∙ Cardiac ejection fraction ≥ 45%
∙ Baseline oxygen saturation ≥ 92% on room air
• Females of childbearing potential must have a negative serum or urine pregnancy test (females who have undergone surgical sterilization or who have been postmenopausal for at least 12 months are not considered to be of childbearing potential).