Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 1, Multicenter, Open-Label Study of JCAR017, CD19-targeted Chimeric Antigen Receptor (CAR) T Cells, for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL)
Brief Summary: This open-label Phase 1 study will evaluate the safety, PK, and antitumor activity of modified T cells (JCAR017) administered to adult patients with relapsed or refractory B-cell NHL. The dose and schedule of JCAR017 will be evaluated and modified, as needed, for safety and antitumor activity. We will also determine how long the modified T cells stay in the patient's body and how well JCAR017 works in treating patients with non-Hodgkin's lymphoma whose disease has come back or has not responded to treatment.


Options:
A: Inclusion Criteria:

INCLUSION CRITERIA FOR SCREENING:

* Relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS); high grade B cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements; primary mediastinal B-cell lymphoma (PMBCL); or DLBCL transformed from indolent histology with one of the following:

  * Persistent disease after first-line chemo-immunotherapy
  * Relapse after first-line chemo-immunotherapy and not eligible for autologous hematopoietic stem cell transplant (HCT)
  * Relapse or persistent disease after at least two lines of therapy or after autologous HCT
* Ability to understand and provide informed consent

INCLUSION CRITERIA FOR LEUKAPHERESIS AND PRE-THERAPY EVALUATION:

* Screening evaluation appropriate for leukapheresis and T-cell collection
* Evidence of CD19 expression on any prior or current tumor specimen or a high likelihood of CD19 expression based on disease histology

INCLUSION CRITERIA FOR LYMPHODEPLETION CHEMOTHERAPY, JCAR014 AND DURVALUMAB:

* Successful collection of T cells for JCAR014 manufacturing
* Documentation of CD19 expression on any prior or current tumor biopsy
* Internal review of histology
* Detectable positron emission tomography (PET)-positive disease
* Karnofsky performance status \>= 60%
* Assessed by the investigator to have adequate bone marrow function to receive lymphodepleting conditioning chemotherapy
* Serum creatinine \< 1.5 x age-adjusted upper limit of normal (ULN)
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3 x ULN and total bilirubin =\< 2 x ULN
* Adequate pulmonary function, defined as Common Terminology Criteria for Adverse Events (CTCAE) grade =\< 1 dyspnea and oxygen saturation (SaO2) \>= 92% on room air; patients with clinically significant pulmonary dysfunction, as determined by medical history and physical exam should undergo pulmonary function testing and must have a forced expiratory volume in 1 second (FEV1) \>= 50% of predicted value or diffusing capacity of the lung for carbon monoxide (DLCO; corrected) \>= 40% of predicted value
* Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) \>= 35% as assessed by echocardiogram (ECHO) or multiple uptake gated acquisition (MUGA)
* Women of reproductive potential (defined as all women physiologically capable of becoming pregnant) must agree to use suitable methods of contraception for 90 days after the last dose of study therapy (durvalumab or JCAR014)
* Males who have partners of reproductive potential must agree to use an effective barrier contraceptive method for 90 days after the last dose of study therapy (durvalumab or JCAR014)

Exclusion Criteria:

EXCLUSION CRITERIA FOR SCREENING:

* Subjects with known active central nervous system (CNS) involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging
* Planned use of corticosteroids (\> 10 mg/day prednisone or equivalent) or other systemic immunosuppression within 4 days prior to leukapheresis; topical and/or inhaled steroids are permitted
* Prior treatment with any CD19 CAR T-cell therapy
* Prior allogeneic HCT
* Known active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection
* Pregnant or breastfeeding women
* Known exclusion criteria for leukapheresis, JCAR014, or durvalumab therapy

EXCLUSION CRITERIA FOR LEUKAPHERESIS AND PRE-THERAPY EVALUATION:

* Subjects with known active central nervous system (CNS) involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging
* Prior treatment with programmed cell death (PD)-1, PD-ligand (L)1, cytotoxic T lymphocyte-associated protein 4 (CTLA 4) targeted therapy, or tumor necrosis factor receptor superfamily (TNFRSF) agonists including CD134 (OX40), CD27, CD137 (4-1BB), and CD357 (glucocorticoid-induced tumor necrosis factor receptor family-related protein \[GITR\])
* Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., ulcerative colitis, Crohn's disease\], celiac disease, or other serious chronic gastrointestinal conditions associated with diarrhea; autoimmune vasculitis; systemic lupus erythematosus; Wegener syndrome \[granulomatosis with polyangiitis\]; myasthenia gravis; Graves' disease; rheumatoid arthritis, hypophysitis, uveitis, etc.) within 3 years prior to the planned start of treatment; the following are exceptions to this criterion:

  * Vitiligo
  * Alopecia
  * Hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
  * Psoriasis not requiring systemic treatment
  * Other conditions considered to be low risk of serious deterioration by the principal investigator (PI)
* History of any one of the following cardiovascular conditions within the past 6 months: class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, or unstable angina; history of other clinically significant cardiac disease that, in the opinion of the PI or designee, is a contraindication to lymphodepleting chemotherapy, JCAR014 infusion, or durvalumab infusion is also excluded
* History or presence of clinically relevant CNS pathology such as epilepsy, seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, or psychosis; history of other organic brain syndrome that in the opinion of the PI or designee is a contraindication to lymphodepleting chemotherapy, JCAR014 infusion or durvalumab infusion
* History of solid organ transplantation

EXCLUSION CRITERIA FOR LYMPHODEPLETION CHEMOTHERAPY, JCAR014 AND DURVALUMAB:

* For lymphodepletion chemotherapy, JCAR014 and durvalumab: Subjects with known active CNS involvement by malignancy; subjects with prior CNS disease that has been effectively treated will be eligible if treatment was completed at least 3 months prior to enrollment and there is no evidence of disease or stable abnormalities on repeat imaging
* Uncontrolled infection
* Receipt of live, attenuated vaccine within 28 days prior to the first dose of durvalumab (Note: enrolled patients should not receive live vaccine during the study and for 180 days after the last dose of durvalumab)
* Planned use of corticosteroids (\> 10 mg/day prednisone or equivalent) or other systemic immunosuppression is not permitted within 72 hours prior to JCAR014 infusion; topical and/or inhaled steroids are permitted.
B: Inclusion Criteria:

1. Age ≥18 years
2. Relapsed or refractory B-cell NHL, including

   1. DLBCL cohort (no longer enrolling): DLBCL, not otherwise specified (NOS; includes transformed DLBCL from indolent histology \[tDLBCL\]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (Swerdlow 2016), primary mediastinal B-cell lymphoma (PMBCL), and follicular lymphoma Grade 3B. Subjects must have been treated with an anthracycline and rituximab (or other CD20-targeted agent) and have relapsed or refractory disease after at least 2 lines of systemic therapy or after auto-HSCT.
   2. MCL cohort: MCL (diagnosis must be confirmed with cyclin D1 expression or evidence of t(11;14) by cytogenetics, fluorescent in situ hybridization \[FISH\], or PCR) with relapsed or refractory disease after at least 2 prior lines of systemic MCL therapy. Subjects must have been treated with an alkylating agent, Bruton's tyrosine kinase inhibitor (BTKi), and rituximab (or other CD20-targeted agent).
3. PET-positive disease by Lugano classification
4. 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.
5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
6. Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function
7. Adequate vascular access for leukapheresis procedure
8. Participants who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy.
9. Participants must agree to use appropriate contraception.

Exclusion Criteria:

1. Active central nervous system (CNS)-only involvement by malignancy (note: participants with secondary CNS involvement are allowed on study)
2. History of other primary malignancy not in remission for at least 2 years (The following are exempt from the 2-year limit: nonmelanoma skin cancer, definitively treated stage 1 solid tumor with low risk for recurrence, curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on Pap smear)
3. Treatment with alemtuzumab within 6 months of leukapheresis or fludarabine or cladribine within 3 months of leukapheresis
4. Active hepatitis B, hepatitis C, or Subjects with a history of or active human immunodeficiency virus (HIV) infectionare excluded. Subjects with active hepatitis B, or active hepatitis C are also excluded. Subjects with a negative 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
5. Uncontrolled systemic fungal, bacterial, viral, or other infection
6. Presence of graft-vs-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. Use of the following:

    * Therapeutic doses of corticosteroids (defined as \>20 mg/day prednisone or equivalent) within 7 days of leukapheresis or 72 hours prior to JCAR017 administration. Physiologic replacement, topical, and inhaled steroids are permitted.
    * Low dose chemotherapy (e.g., vincristine, rituximab, cyclophosphamide ≤300 mg/m2) given after leukapheresis to maintain disease control must be stopped ≥7 days prior to lymphodepleting chemotherapy.
    * Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) within 1 week of leukapheresis. Oral chemotherapeutic agents, including lenalidomide and ibrutinib, are allowed if at least 3 half-lives have elapsed prior to leukapheresis.
    * Lymphotoxic chemotherapeutic agents (e.g., cyclophosphamide, ifosfamide, bendamustine) within 2 weeks of leukapheresis.
    * Experimental agents within 4 weeks of leukapheresis unless no response or disease progression is documented on the experimental therapy and at least 3 half-lives have elapsed prior to leukapheresis
    * Immunosuppressive therapies within 4 weeks of leukapheresis and JCAR017 administration (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolyate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-TNF, anti IL6, or anti-IL6R)
    * Donor lymphocyte infusions (DLI) within 6 weeks of JCAR017 administration
    * Radiation within 6 weeks of leukapheresis. Subjects must have progressive disease in irradiated lesions or have additional non-irradiated, PET-positive lesions to be eligible. Radiation to a single lesion, if additional non-irradiated PET-positive lesions are present, is allowed up to 2 weeks prior to leukapheresis.
    * Allo-HSCT within 90 days of leukapheresis
11. Prior CAR T-cell or other genetically-modified T-cell therapy, with the exception of prior JCAR017 treatment in this protocol for subjects receiving retreatment
12. Progressive vascular tumor invasion, thrombosis, or embolism
13. Venous thrombosis or embolism not managed on a stable regimen of anticoagulation
C: Inclusion Criteria:

* Metastatic Melanoma patients failing to prior chemo and immunotherapy with good performance status.

Exclusion Criteria:

* Brain mets
D: 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.

Answer: B