An Open-label, Multi-center, Single-arm Phase 1/2 Study to Assess Tolerability, Safety and Efficacy of CRC01 in Adult Patients With Relapsed or Refractory Large B-cell Lymphoma
This is a multi-center, phase I/II study to determine the efficacy and safety of CRC01 in adult patients with relapsed or refractory large B-cell lymphoma.
• ≥ 19 years of age and provided written informed consent
• Histologically confirmed following large B-cell lymphomas according to the World Health Organization classification 2017
‣ Diffuse large B-cell lymphoma, not otherwise specified Including Large cell transformation from follicular lymphoma (Transformed follicular lymphoma)
⁃ High-grade B-cell lymphoma, not otherwise specified
⁃ High-grade B-cell lymphoma with double-hit/triple-hit
⁃ Primary mediastinal large B cell lymphoma
• Relapsed or refractory disease after ≥ two lines of chemotherapy including rituximab, anthracycline and either having failed autologous Hematopoietic stem cell transplantation (ASCT) or being ineligible for or not consenting to ASCT.
• At least one measurable lesion (Long diameter ≥ 1.5cm)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Adequate renal and hepatic functions based on the laboratory test results
‣ Total Bilirubin ≤ 2.0mg/dL with the exception of patients with Gilbert-Meulengracht syndrome; patients with Gilbert-Meulengracht syndrome may be included if their total bilirubin is ≤ 3 X ULN and direct bilirubin ≤ 1.5 X ULN.
⁃ Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 3 X Upper Limit of Normal (ULN) for age with exception of liver metastasis; patients with liver metastasis may be included if their AST and ALT are ≤ 5 X ULN.
⁃ Serum creatinine ≤ 1.5 X ULN
⁃ Estimated Glomerular Filtration Rate (eGFR) ≥ 60mL/min/1.73m2
• Adequate hematologic function without transfusions within 2 weeks prior to screening for the study defined as followings:
‣ Hemoglobin \> 8.0g/㎗
⁃ Absolute Neutrophil Count (ANC) \> 1,000/㎕
⁃ Absolute Lymphocyte Count (ALC) ≥ 300/㎕
⁃ Platelets ≥ 50,000/㎕
• Must have a minimum level of pulmonary reserve defined as;
‣ ≤ Grade 1 dyspnea per Common terminology criteria for adverse events (CTCAE) v5.0
⁃ pulse oxygenation \> 91% on room air
• Hemodynamically stable, without pericardial effusion and Left Ventricle Ejection Fraction (LVEF) ≥ 50% confirmed by Echocardiogram (ECG) or Multigated Radionuclide Angiography (MUGA)
⁃ Must have an apheresis product of non-mobilized cells accepted for manufacturing
⁃ Life expectancy ≥ 12 weeks
⁃ Women of child-bearing potential and all male participants must agree to use highly effective methods of contraception for at least 12 months following CRC01 infusion and until CRC01 are no longer present by PCR on two consecutive tests