A Phase II, Single Arm, Multicenter Trial to Determine the Efficacy and Safety of CTL019 in Adult Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)
This is a multi-center, phase II study to determine the efficacy and safety of CTL019 in adult patients with relapsed or refractory DLBCL.
• Written informed consent must be obtained prior to any screening procedures
• Histologically confirmed DLBCL at last relapse(by central pathology review before enrolment.
• .- Relapsed or refractory disease after ≥2 lines of chemotherapy including rituximab and anthracycline and either having failed autologous Hematopoietic stem cell transplantation (ASCT), or being ineligible for or not consenting to ASCT
• Measurable disease at time of enrollment
• Life expectancy ≥12 weeks
• Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening
• Adequate organ function:
‣ Renal function defined as:
• A serum creatinine of ≤1.5 x Upper Limit of Normal ULN OR
∙ Estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73 m\^2
⁃ Liver function defined as:
• Alanine Aminotransferase (ALT) ≤ 5 times the Upper Limit of Normal (ULN) for age
∙ Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert-Meulengracht syndrome; patients with Gilbert-Meulengracht syndrome may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
⁃ Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation \> 91% on room air
⁃ Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) ≥ 45% confirmed by echocardiogram or Multigated Radionuclide Angiography (MUGA)
⁃ Adequate bone marrow reserve without transfusions defined as:
• Absolute neutrophil count (ANC) \> 1.000/mm\^3
∙ Absolute lymphocyte count (ALC) ≥ 300/mm\^3 and absolute number of CD3+ T cells \> 150/mm\^3
∙ Platelets ≥ 50.000//mm\^3
∙ Hemoglobin \> 8.0 g/dl
⁃ Must have an apheresis product of non-mobilized cells accepted for manufacturing
⁃ Women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) and all male participants must agree to use highly effective methods of contraception for at least 12 months following CTL019 infusion and until CAR T cells are no longer present by PCR on two consecutive tests