Please select the eligibility criteria that correspond to the clinical trial below.
Title: Clinical Study to Evaluate the Safety and Efficacy of IM19 CAR-T Cell Therapy in Patients With Relapsed or Refractory CD19-positive Non-Hodgkin's Lymphoma
Brief Summary: n this study, approximately 30 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) were recruited for a single reinfusion of IM19-CD28 and IM19-41BB CAR-T cells. Assess the safety, tolerability of treatment, and initially observe the efficacy.


Options:
A: Inclusion Criteria

Patients eligible for inclusion in this study have to meet all of the following criteria:

1. Age ≥18 and ≤70 years.
2. Performance status (ECOG) between 0 and 2.
3. Histologically confirmed CD20+ and/or CD19+ B-cell non-Hodgkin lymphoma (NHL), including the following types defined by WHO 2008:

   * DLBCL not otherwise specified, DLBCL associated with chronic inflammation, and Epstein-Barr virus (EBV)+ DLBCL in the elderly.
   * Primary mediastinal (thymic) large B-cell lymphoma (PMBCL). The mediastinal mass had to have an axial diameter \<5 cm or extranodal lesion size \<3 cm. Patients with large lesions (≥5 cm) were enrolled in our other clinical trial (NCT0334662).
   * Transformed FL (tFL) .
   * FL.
   * Some indolent lymphomas including MCL and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
4. Refractory disease or relapsed after treatment with ≥2 lines of chemotherapy including rituximab and anthracycline and either having failed autologous HSCT or being ineligible for or not consenting to autologous HSCT.

   We defined chemotherapy-refractory disease as meeting one or more of the following criteria:
   * No response to first-line therapy (primary refractory disease).
   * No response to second-line or later therapy.
   * PD as the best response to the most recent therapy regimen.
   * Stable disease (SD) as the best response after at least 2 cycles of the most recent line of therapy with a SD duration of no longer than 6 months from the last dose of therapy.

   Failure following autologous HSCT was defined as follows:
   * PD or relapsed disease ≤12 months after ASCT (requires biopsy-proven recurrence in relapsed subjects).
   * No response or relapse after salvage therapy is given post-ASCT.
5. PD or relapse ≥3 months after treatment with a targeted CD19 therapy, including CD19-CAR T cells or anti-CD19/anti-CD3.
6. Successful leukapheresis assessment and pre-culture of T cells.
7. Life expectancy \> 3 months.
8. Adequate organ function:

   * Creatinine \< 1.6 mg/dL (140 µmol/L) or creatinine clearance ≥60 mL/min.
   * ALT/AST \< 3× upper limit of the normal range.
   * Bilirubin \<2.0 mg/dL unless the subject had Gilbert's Syndrome (\<3.0 mg/dL).
   * A minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnoea and pulse oxygenation \> 91% with room air. No clinically significant pleural effusion.
   * Cardiac ejection fraction ≥50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings.
9. An adequate bone marrow reserve defined as:

   * Absolute neutrophil count (ANC)\>1,000/mm3.
   * Absolute lymphocyte count (ALC)≥300/mm3.
   * Platelet count ≥ 50,000/mm3.
   * Haemoglobin \> 7.0 mg/dL.
10. Measurable or assessable disease according to the "IWG Response Criteria for Malignant Lymphoma" (Cheson 2007). Patients in CR with no evidence of disease were not eligible.
11. Informed consent/assent requiring that all patients have the ability to understand and the willingness to provide written informed consent.

Exclusion Criteria:

Patients eligible for this study must not meet any of the following criteria:

1. Patients with definite involvement of gastrointestinal tract. Endoscopy should be performed to conform gastrointestinal involvement for patients suspected. However, patients with central nervous system (CNS) involvement were cautiously enrolled in this clinical study.
2. CD19 CAR T cell treatment failure or recurrence, detection of a clear HAMA effect, or negative tumour puncture detection of CD19 and CD20.
3. Pregnant or lactating women.
4. Uncontrolled active bacterial or viral infection. (active hepatitis B or hepatitis C infection, HIV infection) or treponema pallidum infection.
5. Class III/IV cardiovascular disability according to the New York Heart Association Classification and a cardiac ejection fraction ≥50%.
6. History of allogeneic stem cell transplantation.
7. Any autoimmune disease or primary immunodeficiency.
8. Requirement for urgent therapy due to tumour mass effects such as respiratory obstruction or blood vessel compression.
9. Current or expected need for systemic corticosteroid therapy.
10. Any organ failure.
11. The patients with the second tumour requiring for therapy or intervention.
12. Subjects considered unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or comply with the study requirements for participation according to the investigator's judgement.
B: Inclusion criteria:

1. Relapsed or refractory CD19-positive non-Hodgkin lymphoma (NHL) patients. 1 Diffuse large B lymphoma (DLBCL), follicular lymphoma (FL), primary mediastinal B-cell lymphoma (PMBCL) patients meet one of the following conditions: I Patients who have relapsed or are refractory after at least 2 previous treatments; II Patients who have relapsed after transplantation. 2 Patients with relapsed or refractory mantle cell lymphoma after at least one treatment.
2. Patients must have evaluable disease evidence;
3. Age ≥ 18 years old;
4. The expected life span is more than 3 months;
5. ECOG score 0-2 points (see Attachment 2);
6. Women of childbearing age have a negative blood pregnancy test before the start of the trial and agree to have effective contraceptive measures during the trial until the last follow-up;
7. Those who voluntarily participate in the trial and sign the informed consent.

Exclusion criteria:

1. Patients with high-risk organ involvement: tumors invade one of the central nervous system, gastrointestinal tract, lungs, pericardium, and large vessels;
2. Those who have a graft-versus-host response and need to use immunosuppressive drugs; or who have a disease of the autoimmune system;
3. Use chemotherapy or radiotherapy within 3 days before the blood collection period;
4. Those who have used systemic steroids within the 5 days prior to the blood sampling period (except recently or currently using inhaled steroids);
5. Use stimulating bone marrow hematopoietic cells to produce drugs (whitening needles, etc.) within 5 days before the blood collection period;
6. Those who have previously used any gene therapy products;
7. History of epilepsy or other diseases of the central nervous system;
8. New York Heart Association (NYHA) class III or above (see Annex 3);
9. creatinine\> 1.5 times the upper limit of normal or ALT / AST\> 3 times the upper limit of normal or bilirubin\> 2 times the normal upper limit;
10. active Hepatitis B or Hepatitis C virus, HIV or other untreated active infections;
11. pregnant or lactating women;
12. suffer from other uncontrolled diseases that the researcher considers inappropriate;
13. Any condition that the investigator believes may increase the subject's risk or interfere with the test results.
C: Inclusion Criteria:

1. Subject is ≥ 18 years and ≤ 75 years of age at the time of signing the informed consent form (ICF).
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
3. Histologically proven diffuse large B-cell lymphoma (DLBCL) NOS (de novo or transformed indolent NHL), high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple-hit lymphoma \[DHL/THL\]), primary mediastinal (thymic) large B-cell lymphoma (PMBCL), T cell/histiocyte-rich large B-cell lymphoma (THRBCL) or follicular lymphoma grade 3B. Enough tumor material must be available for confirmation by central pathology.
4. Refractory or relapsed within 12 months from CD20 antibody and anthracycline containing first line therapy.
5. \[18F\] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion at screening. (Deauville score 4 or 5)
6. Adequate organ function
7. Participants must agree to use effective contraception

Exclusion Criteria:

1. Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
2. Subjects planned to undergo allogeneic stem cell transplantation.
3. Subjects with, primary cutaneous large B-cell lymphoma, EBV (Epstein-Barr virus) positive DLBCL, Burkitt lymphoma or transformation from chronic lymphocytic leukemia/small lymphocytic lymphoma (Richter transformation).
4. Subjects with prior history of malignancies, other than aggressive R/R NHL, unless the subject has been free of the disease for ≥ 2 years with the exception of the following noninvasive malignancies:

   * Basal cell carcinoma of the skin
   * Squamous cell carcinoma of the skin
   * Carcinoma in situ of the cervix
   * Carcinoma in situ of the breast
   * Incidental histologic finding of prostate cancer (T1a or T1b using the TNM \[tumor, nodes, metastasis\] clinical staging system) or prostate cancer that is curative.
   * Other completely resected stage 1 solid tumor with low risk for recurrence
5. Treatment with any prior gene therapy product.
6. Subjects who have received previous CD19-targeted therapy.
7. Subjects with active hepatitis B, or active hepatitis C are excluded. Subjects with negative polymerase chain reaction (PCR) assay for viral load for hepatitis B or C are permitted. Subjects positive for hepatitis B surface antigen and/or anti-hepatitis B core antibody with negative viral load are eligible and should be considered for prophylactic antiviral therapy. Subjects with a history of or active human immunodeficiency virus (HIV) are excluded.
8. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
9. Active autoimmune disease requiring immunosuppressive therapy.
10. History of any one of the following cardiovascular conditions within the past 6 months prior to signing the ICF: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease.
11. History or presence of clinically relevant central nervous system (CNS) pathology
12. Pregnant or nursing (lactating) women.
D: Inclusion Criteria:

* Subjects must meet all of the following criteria to be enrolled in this study:

  1. Age ≥ 18 years at the time of consent
  2. Signed written informed consent obtained prior to any study procedures
  3. Relapsed or refractory B-cell NHL.
  4. PET-positive disease BY Lugano classification
  5. Archived tumor biopsy tissue available from the last relapse and corresponding pathology report available or, if at least one tumor-involved site is deemed accessible at time of screening, willing to undergo pre-treatment biopsy (excisional when possible) for disease confirmation. If a subject has never had a complete response, a sample from the most recent biopsy is acceptable.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  7. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function
  8. Adequate vascular access for leukapheresis procedure
  9. Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy
  10. Subjects must agree to use appropriate contraception.

Exclusion Criteria:

* Subjects who meet any of the following criteria will be excluded from participation in this study:

  1. Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study)
  2. History of another primary malignancy that has not been in remission for at least 2 years.
  3. Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis
  4. Active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection at the time of screening
  5. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis or JWCAR029 administration
  6. Presence of acute or chronic graft-versus-host disease (GVHD)
  7. History of cardiovascular disease
  8. History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis
  9. Pregnant or nursing women.
  10. Prior CAR T-cell or other genetically-modified T-cell therapy, with the exception of prior JWCAR029 treatment in this protocol for subjects receiving retreatment

Answer: B