Inclusion Criteria:

• Subject is ≥ 18 years and ≤ 75 years of age at the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• ECOG performance status ≤ 1.
• 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 (FL3B). Enough tumor material must be available for confirmation by central pathology. If archival sample is before most recent relapse or if there is no or insufficient archival sample is available, a new tumor biopsy is mandated to confirm diagnosis. If the patient is refractory to first line of treatment, a tumor biopsy sample from disease diagnosis can be used if enough archival material is available.
  • Note: Subjects with secondary CNS involvement are eligible. Subject selection must consider clinical risk factors for severe adverse events (AEs) and alternative treatment options. Subjects should only be enrolled if the  Investigator assesses that the potential benefit outweighs the risk for the subject.
• Refractory disease (SD, PD, PR or CR with relapse before 3 months) or relapsed (disease (defined as CR with relapse on or after lasting at least 3 months) within but no more than 12 months), to CD20 antibody and anthracycline containing first-line therapy for disease under study.
  • Note: The time of relapse is calculated from the date of the first disease assessment confirming a CR obtained with first-line treatment for disease under study, to the date of first assessment demonstrating a relapse.
• [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion per Lugano criteria at screening (Deauville score 4 or 5).
• Adequate organ function, defined as:
  • Adequate bone marrow function defined as: absolute neutrophil count (ANC) ≥ 1.0 x 10^9 cells/L and platelets ≥ 50 x 10^9 cells/L in absence of bone marrow involvement;
  • Serum creatinine < 1.5 x upper limit of normal (ULN) or creatinine clearance > 45 mL/min (estimated by Cockcroft Gault);
  • Alanine aminotransferase (ALT) ≤ 5 x ULN and total bilirubin < 2.0 mg/dL (or < 3.0 mg/dL for subjects with Gilbert's syndrome or lymphomatous infiltration of the liver);
  • Adequate pulmonary function, defined as ≤ Grade 1 dyspnea according to Common Terminology Criteria for Adverse Events (CTCAE) and oxygen saturation (SaO2) ≥ 92% on room air and FEV1 ≥ 50%;
  • Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) ≥ 40% as assessed by echocardiogram (ECHO) or multi-gated acquisition scan (MUGA) performed within 4 weeks of randomization.
• Adequate vascular access for leukapheresis.
• Subjects must agree to not donate blood, organs, sperm or semen, and egg cells for usage in other individuals for at least 12 months following lympho-depleting chemotherapy. There is insufficient exposure data to provide any recommendation concerning the duration of refraining from tissue donation following treatment with JCAR017. Therefore, subjects treated with JCAR017 should not donate blood, organs, sperm or semen and egg cells for usage in other individuals for at least 12 months following lympho-depleting chemotherapy.
• Females of childbearing potential (FCBP*) must:
  • Have a negative pregnancy test (2 for Arm B) as verified by the Investigator prior to starting study therapy. (one negative serum beta-human chorionic gonadotropin [ßhCG] pregnancy test result at screening [Arm A and B], and within 7 days prior to the first dose of lympho-depleting chemotherapy [Arm B and cross over]). She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence** from heterosexual contact.
  • Either commit to true abstinence** from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with, effective contraception without interruption. Contraception methods must include 1 highly effective method of contraception from screening until at least 12 months after receiving lympho-depleting chemotherapy or until 12 months after the last chemotherapy, whichever is later.
  • Agree to abstain from breastfeeding during study participation and for at least 1 year after lympho-depleting chemotherapy.
  • There is insufficient exposure data to provide any recommendation concerning the duration of contraception and the abstaining from breastfeeding following treatment with JCAR017. Any decision regarding contraception and breastfeeding after JCAR017 infusion should be discussed with the treating physician.
    • Note: Highly effective methods are defined as those that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly.
• The following are examples of highly effective methods of contraception:
  • Intrauterine device (IUD);
  • Hormonal (birth control pill, injections, implants);
  • Tubal ligation;
  • Partner's vasectomy.
• Male subjects must:
  • Practice true abstinence** (which must be reviewed on a monthly basis) or agree to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and for 12 months after lympho-depleting chemotherapy and for 12 months after the last chemotherapy, whichever is later, even if he has undergone a successful vasectomy. There is insufficient exposure data to provide any recommendation concerning the duration of contraception following treatment with JCAR017. Any decision regarding contraception after JCAR017 infusion should be discussed with the treating physician.
  • * A female subject of childbearing potential (FCBP) is a female who:
    • has achieved menarche at some point;
    • has not undergone a hysterectomy or bilateral oophorectomy;
    • has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 12 consecutive months (ie, has had menses at any time in the preceding 12 consecutive months).
  • **True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. In contrast, periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.

Exclusion Criteria:

The presence of any of the following will exclude a subject from randomization:

• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study based on investigator´s judgment.
• Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study based on investigator´s judgment.
• Subject has any condition that confounds the ability to interpret data from the study based on investigator´s judgment.
• Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
• Subjects planned to undergo allogeneic stem cell transplantation.
• 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).
• 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.
• Treatment with any prior gene therapy product.
• Subjects who have received previous CD19-targeted therapy.
• 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.
• Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
• Active autoimmune disease requiring immunosuppressive therapy.
• 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.
• History or presence of clinically relevant central nervous system (CNS) pathology such as epilepsy, seizure, aphasia, stroke, cerebral edema, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis.
• Progressive vascular tumor invasion.
• Venous thrombosis or embolism not managed on a stable regimen of anticoagulation.
• Pregnant or nursing (lactating) women.
• Use of the following:
  • Therapeutic doses of corticosteroids (defined as > 20 mg/day prednisone or equivalent) within 7 days prior to unstimulated leukapheresis. Physiologic replacement, topical, and inhaled steroids are permitted.
  • Cytotoxic chemotherapeutic agents that are not considered lymphotoxic (see below) and intrathecal (IT) chemotherapy must be stopped ≥ 7 days prior to unstimulated leukapheresis.
  • Lymphotoxic chemotherapeutic agents (e.g., cyclophosphamide, ifosfamide, bendamustine) 2 weeks prior to unstimulated leukapheresis.
  • Experimental agents within 4 weeks prior to signing the ICF unless no response or progressive disease (PD) is documented on the experimental therapy and at least 3 half-lives have elapsed prior to unstimulated leukapheresis.
  • Immunosuppressive therapies within 4 weeks prior to unstimulated leukapheresis (e.g., calcineurin inhibitors, methotrexate or other chemotherapeutics, mycophenolate, rapamycin, thalidomide, immunosuppressive antibodies such as anti-tumor necrosis factor [TNF], anti-IL-6, or anti-IL-6R).
  • Radiation within 4 weeks prior to signing the ICF. 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, measurable PETpositive lesions are present, is allowed up to 2 weeks prior to unstimulated leukapheresis.
  • Systemic immunostimulatory agents (including but not limited to interferon and IL-2) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to JCAR017 infusion.
• Known allergy to DMSO or Dextran.