B-Cell Lymphoma Clinical Trials

• ≥ 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

• ≥ 19 years of age and provided written informed consent to voluntarily participate in this trial

• Relapsed or refractory B-cell lymphoblastic leukemia with one of the following:

‣ Primary refractory: Newly diagnosed and refractory to 2 or more cycles of standard chemotherapy

⁃ Relapsed within 12 months of the first complete remission

⁃ Chemorefractory: Refractory to 1 cycle of chemotherapy conducted after relapse

⁃ Relapsed after or refractory to two or more lines of chemotherapy

⁃ Relapsed or refractory 100 days after allogeneic HSCT

• (within 4 weeks prior to screening) Blast of \> 5% identified in the BM

• (within 4 weeks prior to screening) BM or peripheral blood blast confirmed CD19-positive.

• Specifically, those with prior treatment with any other anti-CD19 therapy must be confirmed to show CD19 ≥ 90%.

• Philadelphia chromosome positive with one of the following:

‣ Unable to take tyrosine kinase inhibitors (TKIs) due to side effects

⁃ Relapsed or refractory despite treatment with two or more TKIs

• ECOG performance status of 0-1

• Confirmed adequate hematologic function defined as follows:

‣ Absolute neutrophil count (ANC) ≥ 500/μL. However, exceptions are made in cases where the Investigator determines that cytopenia is related to the leukemia and may be recovered with leukemia treatment.

⁃ Platelet count ≥ 50,000/μL. However, exceptions are made in cases where the Investigator determines that cytopenia is related to the leukemia and may be recovered with leukemia treatment.

⁃ Absolute lymphocyte count ≥ 200/μL

• Adequate renal and hepatic functions confirmed based on the laboratory test results:

‣ Total Bilirubin ≤ 2.0 mg/dL (for patients with Gilbert-Meulengracht syndrome, total bilirubin ≤ 3 × ULN and direct bilirubin ≤ 1.5 × ULN)

⁃ AST and ALT ≤ 3 × ULN

⁃ Serum creatinine ≤ 1.5 × ULN or eGFR\* ≥ 45 mL/min/1.73 m2 \*MDRD-GFR (mL/min/1.73 m2) = 186 × (serum creatinine)-1.154 × (age)-0.203 (× 0.742 for females)

• Confirmed to have a minimum level of pulmonary reserve according to the following criteria:

‣ ≤ Grade 1 dyspnea per CTCAE v5.0

⁃ Pulse oxygenation \> 91% on room air

⁃ Hemodynamically stable, without pericardial effusion, and LVEF ≥ 50% confirmed by ECHO or MUGA scan at Screening

⁃ Capable of obtaining through leukapheresis non-mobilized cells adequate for CRC01 manufacturing

⁃ Life expectancy of ≥ 12 weeks

⁃ Consented to comply with the site visit and test schedules for Primary Follow-up and Secondary Follow-up in accordance with the Protocol for the duration of the Study

⁃ WOCBP or male subjects who are willing to use appropriate contraceptive methods\* for at least 12 months following CRC01 treatment and until CRC01 is no longer detected through two consecutive PCR tests \* Hormonal contraceptives, placement of intrauterine system, double barrier method (simultaneous use of contraceptive vaginal diaphragm or cervical cap and male condom, along with spermicide), sterilization (vasectomy, bilateral tubal ligation), etc.