Please select the eligibility criteria that correspond to the clinical trial below.
Title: Immunotherapy With Ex Vivo-Expanded Cord Blood-Derived CAR-NK Cells Combined With High-Dose Chemotherapy and Autologous Stem Cell Transplantation for B-Cell Lymphoma
Brief Summary: This phase I/II trial studies the side effects and best dose of chimeric antigen receptor (CAR).CD19-CD28-zeta-2A-iCasp9-IL15-transduced cord blood NK cells when given together with high-dose chemotherapy and stem cell transplant and to see how well they work in treating participants with B-cell lymphoma. Cord blood-derived CAR-NK cells may react against the B-cell lymphoma cells in the body, which may help to control the disease. Giving chemotherapy before a stem cell transplant may help kill any cancer cells that are in the body and helps make room in the patient's bone marrow for new blood-forming cells (stem cells) to grow. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy.


Options:
A: Key Inclusion Criteria

1. Histologically confirmed:

   * Diffuse Large B Cell Lymphoma (DLBCL)
   * Primary Mediastinal Large B Cell Lymphoma (PMBCL)
   * Transformation Follicular Lymphoma (TFL)
   * High grade B-cell lymphoma (HGBCL)
2. Chemotherapy-refractory disease, defined as one of more of the following:

   * No response to last line of therapy i. Progressive disease (PD) as best response to most recent therapy regimen ii. Stable disease (SD) as best response to most recent therapy with duration no longer than 6 month from last dose of therapy OR
   * Refractory post-autologous stem cell transplant (ASCT) i. Disease progression or relapsed less than or equal to 12 months of ASCT (must have biopsy proven recurrence in relapsed individuals) ii. If salvage therapy is given post-ASCT, the individual must have had no response to or relapsed after the last line of therapy
3. Individuals must have received adequate prior therapy including at a minimum:

   * Anti-cluster of differentiate 20 (CD20) monoclonal antibody unless investigator determines that tumor is CD20-negative and
   * an anthracycline containing chemotherapy regimen
   * for individual with transformed FL must have chemorefractory disease after transformation to DLBCL.
4. At least one measurable lesion per revised international working group (IWG Response Criteria
5. Eastern cooperative oncology group (ECOG) performance status of 0 or 1
6. Absolute neutrophil count (ANC) ≥ 1000/microliters (uL)
7. Absolute lymphocyte count ≥ 100/uL
8. Platelet count ≥ 75,000/uL
9. Adequate renal, hepatic, pulmonary and cardiac function defined as:

   * Creatinine clearance (as estimated by Cockcroft Gault) \> 60 mL/min
   * Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) \< 2.5 upper limit of normal (ULN)
   * Total bilirubin \< 1.5 mg/dL, except in individuals with Gilbert's syndrome
   * Cardiac ejection fraction \>50%, no evidence of pericardial effusion as determined by an echocardiogram (ECHO), and no clinically significant pleural effusion
   * Baseline oxygen saturation \>92% on room air
10. All individuals or legally appointed representatives/caregivers, must personally sign and date the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved consent form before initiating any study specific procedures or activities.
11. Relapsed or refractory large B-cell lymphoma including DLBCL, PMBCL, TFL, and HGBCL after two systemic lines of therapy

Key Exclusion Criteria

1. History of malignancy other than nonmelanoma skin cancer or carcinoma in situ (e.g. cervix, bladder, breast) or follicular lymphoma unless disease free for at least 3 years
2. History of allogeneic stem cell transplantation
3. Prior chimeric antigen receptor (CAR) therapy or other genetically modified T cell therapy
4. Presence of fungal, bacterial, viral, or other infection that is uncontrolled or requiring intravenous (IV) antimicrobials for management. Simple urinary tract infection (UTI) and uncomplicated bacterial pharyngitis are permitted if responding to active treatment
5. History of human immunodeficiency virus (HIV) infection or acute or chronic active hepatitis B or C infection. Individuals with history of hepatitis infection must have cleared their infection as determined by standard serological and genetic testing per current Infectious Diseases Society of America (IDSA) guidelines
6. Individuals with detectable cerebrospinal fluid malignant cells, or brain metastases, or with a history of central nervous system (CNS) lymphoma or primary CNS lymphoma, cerebrospinal fluid malignant cells or brain metastases
7. History or presence of CNS disorder such as seizure disorder, cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or any autoimmune disease with CNS involvement

Note: Other protocol defined Inclusion/Exclusion criteria may apply.
B: Inclusion Criteria:

* 18 Years to 70 Years, Male and female
* Survival time\>12 weeks
* B cell lymphomas diagnosed by Physical examination,pathological examination,Laboratory tests and imaging tests
* Chemotherapy failure or recurrent B cell lymphomas
* Creatinine\< 2.5mg/dl
* Glutamic-pyruvic transaminase, glutamic oxalacetic transaminase\< 3 fold of normal level
* Bilirubin\<2.0mg/dl
* Karnofsky Performance Status\>50% at the time of screening
* Adequate pulmonary, renal, hepatic, and cardiac function
* Fail in autologous or allogenic haemopoietic stem cell transplantation
* Free of leukocytes removal contraindications
* Voluntarily join CAR-T clinical trial
* Understand and sign written informed consent

Exclusion Criteria:

* Pregnant or nursing women or women with pregnancy plan in half a year
* Any infectious disease (HIV, active tuberculosis, ect.)
* Active hepatitis B, active hepatitis C infection
* Feasibility assessment proves that the efficiency of transduction of lymphocyte is below 10% or the lymphocyte amplification is below 5 fold with the costimulation of cluster of differentiation 3(CD 3)and cluster of differentiation 8(CD 8)
* Abnormal vital signs or cannot cooperate with the inspectors
* mental or psychological disease cannot cooperate with treatment and curative effect evaluation
* Highly allergic constitution or history of severe allergies, especially allergy to interleukin-2(IL-2)
* General infection or local severe infection, or other infection that is not controlled
* Dysfunction in lung, heart, kidney and brain
* Severe autoimmune diseases
* Other symptoms that are not applicable for CAR-T
C: Inclusion Criteria:

1. Age 18-70.
2. Patients with B-cell lymphoma who are candidates to autologous stem-cell transplantation, including: 1. Primary refractory or relapsed diffuse large B-cell lymphoma in response to salvage treatment. 2. Primary refractory or relapsed follicular lymphoma or other indolent B-cell histology in response to salvage treatment. 3. Chemosensitive mantle-cell lymphoma in first or later line of treatment. 4. Patients with B cell lymphoma (all CD19+ NHL) with progressive or refractory disease who would otherwise not be candidates for autologous stem cell transplantation.
3. Adequate organ function: Renal: Creatinine clearance (as estimated by Cockcroft Gault) \>/= 60 cc/min. Hepatic: ALT/AST \</= 2.5 x ULN or \</= 5 x ULN if documented liver metastases, Total bilirubin \</= 1.5 mg/dL, except in subjects with Gilbert's Syndrome in whom total bilirubin must be \</= 3.0 mg/dL. Cardiac: Cardiac ejection fraction \>/= 50%, no evidence of pericardial effusion as determined by an ECHO, and no clinically significant ECG findings. Pulmonary: No clinically significant pleural effusion, Baseline oxygen saturation \> 92% on room air.
4. Patients must have a cord blood unit available which is matched with the patient at 4, 5, or 6/6 HLA class I (serological) and II (molecular) antigens.
5. Availability of autologous peripheral blood stem cell graft, containing at least 6.0 x 10\^6 CD34+ cells/kg.
6. Performance status \< 2 (ECOG).
7. Negative Beta HCG in woman with child-bearing potential.
8. All participants who are able to have children must practice effective birth control while on study. Acceptable forms of birth control for female patients include: hormonal birth control, intrauterine device, diaphragm with spermicide, condom with spermicide, or abstinence, for the length of the study. If the participant is a female and becomes pregnant or suspects pregnancy, she must immediately notify her doctor. If the participant becomes pregnant during this study, she will be taken off this study. Men who are able to have children must use effective birth control while on the study. If the male participant fathers a child or suspects that he has fathered a child while on the study, he must immediately notify his doctor.
9. Signed consent to long-term follow-up protocol PA17-0483.

Exclusion Criteria:

1. Primary CNS lymphoma.
2. Grade \>/= 3 non-hematologic toxicity from prior therapy that has not resolved to \</= G1.
3. Prior whole brain irradiation.
4. Active hepatitis B, either active carrier (HBsAg +) or viremic (HBV DNA \>/= 10,000 copies/mL, or \>/= 2,000 IU/mL).
5. Evidence of either cirrhosis or stage 3-4 liver fibrosis in patients with chronic hepatitis C or positive hepatitis C serology.
6. Active infection requiring parenteral antibiotics.
7. HIV infection.
8. Radiation therapy in the month prior to enroll.
9. Presence of fungal, bacterial, viral, or other infection requiring IV antimicrobials for management. Note: Simple UTI and uncomplicated bacterial pharyngitis are permitted if responding to active treatment.
10. Concomitant use of other investigational agents.
D: Inclusion Criteria:

* signed written informed consent obtained prior to study procedures
* histologically-confirmed relapsed or refractory CD20+ B-cell lymphoma of one of the following types, with documented disease progression or recurrence following the immediate prior therapy: DLBCL (regardless of cell of origin or underlying molecular genetics), MCL, PMBCL, Gr3b-FL, TH-FL (prior dx of FL before transforming to DLBCL).
* biopsy-confirmed CD20+ expression of the underlying malignancy with disease progression following immediate prior therapy
* at least 1 measurable lesion on imaging.
* must have received adequate prior therapy for the underlying CD20+ B-cell lymphoma, defined as an anti-CD20 mAb in combination with an anthracycline-containing chemotherapy regimen (i.e. chemo-immunotherapy) and at least one of the following:

  * biopsy-proven refractory disease after frontline chemo-immunotherapy
  * relapse within 1 year from frontline chemo-immunotherapy and ineligible for autologous hematopoietic stem cell transplant (auto-HSCT)
  * for subjects with DLBCL, PMBCL, and Gr3b-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT
  * for subjects with TH-FL: relapsed or refractory disease following at least 2 prior regimens or following an auto-HSCT. At least 1 prior regimen with an anti-CD20 mAb in combination with chemotherapy is required following documented transformation
  * for subjects with MCL (confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization (FISH) or polymerase chain reaction (PCR): relapsed or refractory disease after at least 1 prior regimen with chemo-immunotherapy (prior auto-HSCT is allowable)
* ECOG 0 or 1
* life expectancy of at least 6 months
* platelet count greater than 50,000/µL

Exclusion Criteria:

* known active central nervous system (CNS) involvement by malignancy.
* prior treatment as follows:

  * alemtuzumab within 6 months of enrollment
  * fludarabine, cladribine, or clofarabine within 3 months of enrollment
  * external beam radiation within 2 weeks of enrollment
  * mAb (including rituximab) within 2 weeks of enrollment
  * other lymphotoxic chemotherapy (including steroids except as below) within 2 weeks of enrollment
  * experimental agents within 3 half-lives prior to enrollment, unless progression is documented on therapy
* clinically significant cardiac disease
* clinically significant active infection
* clinically significant CNS disorder
* clinical history, prior diagnosis, or overt evidence of autoimmune disease
* known bone marrow involvement due to underlying malignant disease, in dose-escalation phase only

Answer: C