Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase I Trial of High Dose Therapy and Autologous Stem Cell Transplantation Followed by Infusion of Chimeric Antigen Receptor (CAR) Modified T-Cells Directed Against CD19+ B-Cells for Relapsed and Refractory Aggressive B Cell Non-Hodgkin Lymphoma
Brief Summary: The purpose of this study is to test the safety of delivering the patients' own immune cells, called T cells, after the high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT).


Options:
A: Inclusion Criteria:

* Written informed consent must be obtained prior to any screening procedures
* Histologically confirmed DLBCL at last relapse(by central pathology review before enrolment.

  .- Relapsed or refractory disease after ≥2 lines of chemotherapy including rituximab and anthracycline and either having failed autologous Hematopoietic stem cell transplantation (ASCT), or being ineligible for or not consenting to ASCT
* Measurable disease at time of enrollment
* Life expectancy ≥12 weeks
* Eastern Cooperative Oncology Group (ECOG) performance status that is either 0 or 1 at screening
* Adequate organ function:

  * Renal function defined as:

    * A serum creatinine of ≤1.5 x Upper Limit of Normal ULN OR
    * Estimated Glomerular Filtration Rate (eGFR) ≥ 60 mL/min/1.73 m\^2
  * Liver function defined as:

    * Alanine Aminotransferase (ALT) ≤ 5 times the Upper Limit of Normal (ULN) for age
    * Bilirubin ≤ 2.0 mg/dl with the exception of patients with Gilbert-Meulengracht syndrome; patients with Gilbert-Meulengracht syndrome may be included if their total bilirubin is ≤ 3.0 x ULN and direct bilirubin ≤ 1.5 x ULN
  * Must have a minimum level of pulmonary reserve defined as ≤ Grade 1 dyspnea and pulse oxygenation \> 91% on room air
  * Hemodynamically stable and Left Ventricle Ejection Fraction (LVEF) ≥ 45% confirmed by echocardiogram or Multigated Radionuclide Angiography (MUGA)
  * Adequate bone marrow reserve without transfusions defined as:

    * Absolute neutrophil count (ANC) \> 1.000/mm\^3
    * Absolute lymphocyte count (ALC) ≥ 300/mm\^3 and absolute number of CD3+ T cells \> 150/mm\^3
    * Platelets ≥ 50.000//mm\^3
    * Hemoglobin \> 8.0 g/dl
  * Must have an apheresis product of non-mobilized cells accepted for manufacturing
  * Women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) and all male participants must agree to use highly effective methods of contraception for at least 12 months following CTL019 infusion and until CAR T cells are no longer present by PCR on two consecutive tests

Exclusion Criteria:

* Prior treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy
* Treatment with any prior gene therapy product
* Active Central Nervous System (CNS) involvement by malignancy
* Prior allogeneic HSCT
* Eligible for and consenting to HSCT
* Chemotherapy other than lymphodepleting chemotherapy within 2 weeks of infusion
* Investigational medicinal product within the last 30 days prior to screening
* The following medications are excluded:

  * Steroids: Therapeutic doses of steroids must be stopped \>72 hours prior to leukapheresis and \>72 hours prior to CTL019 infusion. However, the following physiological replacement doses of steroids are allowed: \< 12 mg/m\^2/day hydrocortisone or equivalent
  * Immunosuppression: Any other immunosuppressive medication must be stopped ≥2 weeks prior to leukapheresis and ≥ 2 weeks prior to CTL019 infusion. This could include check point inhibitors (monoclonal antibodies and small molecule modulators)
  * Antiproliferative therapies other than lymphodepleting chemotherapy within two weeks of leukapheresis and 2 weeks prior to infusion
* Short acting drugs used to treat leukemia or lymphoma (e.g. tyrosine kinase inhibitors, and hydroxyurea) must be stopped \> 72 hour prior to leukapheresis and \> 72 hours prior to CTL019 infusion
* Other cytotoxic drugs, including low dose daily or weekly maintenance chemotherapy, must not be given within 2 weeks prior to leukapheresis and within 2 weeks prior to CTL019 infusion
* Fludarabine may be associated with prolonged lymphopenia. This should be taken into consideration when evaluating the optimal timing for leukapheresis collection.

  * Antibody use including anti-CD20 therapy within 4 weeks prior to infusion or 5 half-lives of the respected antibody, whichever is longer
  * CNS disease prophylaxis must be stopped \> 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate)
* Prior radiation therapy within 2 weeks of infusion
* Active replication of or prior infection with hepatitis B or active hepatitis C( HCV RNA positive )
* HIV positive patients
* Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive ≤ 72 hours prior to infusion)
* Unstable angina and/or myocardial infarction within 6 months prior to screening
* Previous or concurrent malignancy with the following exceptions:

  * Adequately treated basal cell or squamous cell carcinoma (adequate wound healing is required prior to study entry)
  * In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 3 years prior to the study
  * A primary malignancy which has been completely resected and in complete remission for ≥ 5 years
* Pregnant or nursing (lactating) women. NOTE: female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 24 hours before lymphodepletion
* Intolerance to the excipients of the CTL019 cell product
* Cardiac arrhythmia not controlled with medical management
* Prior treatment with any adoptive T cell therapy
* Patients with T-cell rich/histiocyte rich large B-cell lymphoma (THRBCL), primary cutaneous large B-cell lymphoma, primary mediastinal B-cell lymphoma (PMBCL), EBV positive DLBCL of the elderly, Richter's transformation, and Burkitt lymphoma
* Patients with active neurological auto immune or inflammatory disorders (e.g. Guillain Barre Syndrome, Amyptrophic Lateral Sclerosis)
B: Inclusion Criteria:

* Histologically diagnosed as DLBCL according to the NCCN non-Hodgkin's lymphoma Clinical Practice Guidelines (3rd edition 2016)
* Refractory DLBCL
* All subjects must have received adequate prior therapy including anti-CD20 monoclonal antibody (unless tumor is CD20-negative) and an anthracycline containing chemotherapy regimen. The standardized treatment regimens reference to NCCN non-Hodgkin lymphoma Clinical Practice Guidelines (2016 Version 3)
* At least one measurable lesion per revised IWG Response Criteria (the longest diameter of the tumor ≥ 1.5 cm)
* Age 18-70 years old, male or female
* Expected survival ≥ 12 weeks
* ECOG score 0-1
* Subject's left ventricular ejection fraction (LVEF) is ≥ 50% and no evidence of pericardial effusion as determined by an ECHO
* At least 4 weeks from receiving previous treatment (radiotherapy, chemotherapy, monoclonal antibody therapy or other treatments)
* No contraindications of peripheral blood apheresis
* Female subjects in childbearing age, their serum or urine pregnancy test must be negative, and must agree to take effective contraceptive measures during the trial measures
* Volunteered to participate in this study and signed informed consent

Exclusion Criteria:

* Have a history of allergy to cellular products
* Used any genetically modified T cell therapy
* History of allogeneic hematopoietic stem cell transplantation
* Severe active infection (uncomplicated urinary tract infections, bacterial pharyngitis allowed) or currently receiving intravenous antibiotic therapy and received intravenous antibiotic therapy within one week. Prophylactic antibiotic, antiviral and antifungal treatment is permissible
* Hepatitis B or hepatitis C virus infection (including carriers), as well as acquired, congenital immune deficiency diseases, including but not limited to HIV-infected persons
* Patients with class III and IV heart failure according to the NYHA Heart Failure Classifications
* A history of QT prolongation
* A history of epilepsy or other central nervous system disorders
* The patient had a history of other primary cancers, with the following exceptions: Excisional non-melanoma such as cutaneous basal cell carcinoma; Cured in situ carcinoma such as cervical cancer, bladder cancer or breast cancer
* Subjects with any autoimmune disease or any immune deficiency disease or other disease in need of immunosuppressive therapy
* Used of systemic steroids within two weeks (using inhaled steroids is an exception)
* Women who are pregnant or lactating or have breeding intent in 6 months
* Participated in any other clinical trial within three months
* The investigators believe that any increase in the risk of the subject or interference with the results of the trial
C: Transplant eligible patients will be eligible if criteria met per below.

Inclusion Criteria:

* Patients ≥ 18 years of age with aggressive B-cell non-Hodgkin lymphoma subtypes including, relapsed or refractory diffused large B-cell lymphoma (DLBCL), and transformed follicular lymphoma meeting at least one of the following criteria:

  * Bone marrow involvement at the time of relapse or refractory disease and not appropriate for allogeneic transplantation.
  * PET positive disease outside of one radiation port unless single-port disease treated with prior radiotherapy within the port, following \> or = to 2 cycles of salvage chemotherapy, still achieving chemosensitive status 1999 IWG criteria (section 12.2 and 12.383).
* Creatinine ≤ 1.5 mg/100 ml (or measured 24 hour creatinine clearance of ≥ 50 cc/min)
* Bilirubin \<2.0 mg/100 ml, AST and ALT \<3x the upper-limit of normal, PT and PTT \< 2x normal outside the setting of stable chronic anticoagulation therapy,
* Adequate cardiac function (LVEF\>40%) as assessed by ECHO or MUGA scan performed within 1 month of treatment.
* Adequate pulmonary function as assessed by DLCO of \> or = to 45% adjusted for hemoglobin.
* Life expectancy of \> 3 months.

Exclusion Criteria:

* Karnofsky performance status ≤ 70 (see appendix VI).
* Patients with other aggressive B-cell malignancies including, but not limited to: Burkitt lymphoma, transformed CLL/SLL and transformed marginal zone lymphoma that are not included in 6.1 inclusion criteria.
* Patients previously treated with autologous or allogeneic bone marrow or stem cell transplantation are ineligible.
* Other past or current malignancy unless in the opinion of the investigator it does not contraindicate participation in the study.
* Uncontrolled bacterial, viral or fungal infection.
* Patients with HIV, active hepatitis B or hepatitis C infection.
D: Inclusion Criteria:

* Patients must have B-cell non-Hodgkin lymphoma or chronic lymphocytic leukemia/small lymphocytic lymphoma. Eligible lymphoma subtypes include (but not limited to): mantle cell, follicular, lymphoplasmacytic, marginal zone, transformed indolent B cell lymphoma (including transformed chronic lymphoid leukemia \[CLL\]), or diffuse large B cell lymphoma that has relapsed after a response to at least one prior therapy regimen or is refractory to prior therapy; patients with mantle cell lymphoma must have previously been treated with a Bruton tyrosine kinase (BTK) inhibitor and have either had disease progression, intolerance, or exposure to the drug for at least 3 months; patients with CLL/SLL are eligible if they had disease progression or intolerance to BTKis and/or a BCL-2 inhibitors; they are also required to have been treated with the other agent for at least 3 months (i.e. patients with progression/intolerance to BTKi need to be treated with a BCL-2 inhibitor for at least 3 months, and patients with progression/intolerance to BCL-2 inhibitor need at least 3 months of exposure to a BTKi); patients with de novo diffuse large B-cell lymphoma (DLBCL) must meet one of the following criteria:

  * Biopsy-proven refractory disease after a frontline regimen containing both an anthracycline and rituximab or other anti-CD20 antibody (i.e. "primary refractory"), where any disease recurring within 6 months of completion of the regimen is considered refractory
  * Relapsed or refractory disease after at least one of the following:

    * At least 2 lines of therapy (including at least one with an anthracycline and anti-CD20 antibody)
    * Autologous stem cell transplant
    * Allogeneic stem cell transplant
* Patients with large cell lymphoma transformed from indolent lymphomas are eligible if previously treated with anthracycline containing regimen for either the indolent or large cell histology
* Patients with central nervous system (CNS) lymphoma need to meet one of the following criteria:

  * Primary CNS lymphoma:

    * Progressive disease after 3 cycles or an inadequate response after at least 4 cycles of a high-dose methotrexate (MTX) containing regimen in the opinion of the treating physician, OR
    * Not eligible for MTX therapy due to commodities or tolerance issues per treating physician OR
    * Recurrent disease after an initial response to MTX-based treatment
  * Secondary CNS lymphoma:

    * An inadequate rtesponse to at least 2 cycles of a MTX containing regimen, OR
    * Recurrent disease after an initial response to MTX-based treatment
* Patients must be 18 years of age or older, of any gender, race or ethnicity
* Patients must be capable of understanding and providing a written informed consent
* Negative serum pregnancy test within 2 weeks before enrollment for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
* Fertile male and female patients must be willing to use an effective contraceptive method before, during, and for at least 4 months after the CAR T cell infusion
* Patients must have a Karnofsky performance status of \>= 60%
* Confirmation of diagnosis by internal pathology review of initial or subsequent biopsy or other pathologic material at Fred Hutchinson Cancer Research Center (FHCRC)/Seattle Cancer Care Alliance (SCCA)/University of Washington (UW)/Harborview Medical Center (HMC)
* Evidence of CD20 expression by immunohistochemistry or flow cytometry on the tumor specimen obtained with the biopsy performed with screening; if the CD20 expression on the screening tumor biopsy is unclear or could not be assessed due to technical reasons, CD20 expression on a concomitant tumor specimen (such as marrow biopsy or circulating tumor cells) may be used to satisfy this requirement. For CLL and lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (WM) patients, the screening tumor biopsy can we waived for clinical reasons after discussion with the study principal investigator (PI). For patients with CNS lymphoma, a screening tumor biopsy is not required and evidence of CD20 expression can be documented from the original or prior biopsies
* Serum creatinine =\< 2.5
* Total bilirubin =\< 3.0 mg/dL
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 5 x the upper limit of normal
* Adequate pulmonary function, defined as =\< grade 1 dyspnea and saturated oxygen (SaO2) \>= 92% on room air; if pulmonary function test (PFT)s are performed based on the clinical judgment of the treating physician, patients with forced expiratory volume in 1 second (FEV1) \>= 50% of predicted and carbon monoxide diffusing capability (DLCO) (corrected) of \>= 40% of predicted will be eligible
* Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) of \>= 50% as assessed by echocardiogram or multigated acquisition (MUGA) scan, or LVEF of 45-49% and clearance by a cardiologist
* Measurable disease that can be accurately measured in at least one dimension as \>= 1.5 cm with computed tomography (CT), ultrasound, or magnetic resonance imaging (MRI) techniques. Extranodal disease that is measurable by fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) imaging only will also be allowed. Note that if an excisional biopsy was performed that removed the sole site of measurable disease, the patient will not be eligible for leukapheresis and generation of CAR T cell product
* For patients with CNS lymphoma, a lesion \>= 1cm on brain or spine MRI is required
* Patients with waldenstrom macroglobulinemia (WM) without radiologic evidence of disease are eligible if they have measurable disease, as defined by serum monoclonal M-spike of \>= 0.5 g/dL
* ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Absence of uncontrolled active infection (bacterial, fungal, viral, mycobacterial) not responding to treatment with antibiotics, antiviral agents, or antifungal agents
* ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Absence of active autoimmune disease requiring ongoing systemic immunosuppressive therapy
* ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Negative serum pregnancy test within 2 weeks before lymphodepletion chemotherapy for women of childbearing potential, defined as those who have not been surgically sterilized or who have not been free of menses for at least 1 year
* ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: No treatment with any investigational agent on a different clinical trial between enrollment and lymphodepleting chemotherapy
* ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Serum creatinine =\< 2.5
* ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Total bilirubin =\< 3.0 mg/dL
* ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: AST and ALT =\< 5 x the upper limit of normal
* ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Adequate pulmonary function, defined as =\< grade 1 dyspnea and SaO2 \>= 92% on room air; if PFTs are performed based on the clinical judgment of the treating physician, patients with FEV1 \>= 50% of predicted and DLCO (corrected) of \>= 40% of predicted will be eligible
* ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Adequate cardiac function, defined as left ventricular ejection fraction (LVEF) of \>= 50% as assessed by echocardiogram or MUGA scan, or LVEF of 45-49% and clearance by a cardiologist; if subject receives cardiotoxic chemotherapy after enrollment, repeat echocardiogram or MUGA is required to reestablish eligible LVEF
* ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Patients must have a Karnofsky performance status of \>= 60%. Patients with CNS lymphoma with KPS of \>= 50% are eligible if performance status is low because of the active lymphoma
* ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Measurable disease that can be accurately measured in at least one dimension as \>= 1.5 cm with CT, ultrasound, or MRI techniques; extranodal disease that is measurable by FDG-PET imaging only will also be allowed; note that if an excisional biopsy was performed that removed the sole site of measurable disease, the patient is not be eligible for lymphodepletion and CAR T cell infusion; measurable disease can be based on the imaging study done during the screening unless the patient received treatment in the interim, in which case imaging should be repeated. For patients with CNS lymphoma, a lesion \>= 1 cm on the brain or spine MRI is required. Patients with WM without radiologic evidence of disease are eligible if they have measurable disease, as defined by serum IgM level \>= 0.5g/dL
* ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Patients must require no corticosteroid therapy or dose of less than 15 mg per day of prednisone or the equivalent; pulsed corticosteroid dose for disease control is acceptable until the day before the start of lymphodepletion
* ELIGIBILITY FOR LYMPHODEPLETION CHEMOTHERAPY: Patients must have no active acute or chronic GVHD

Exclusion Criteria:

* Active autoimmune disease requiring systemic immunosuppressive therapy
* Patients requiring corticosteroid therapy at a dose of 15 mg or more per day of prednisone or the equivalent; pulsed corticosteroid dose for disease control is acceptable
* Patients who are human immunodeficiency virus (HIV) seropositive
* Women who are pregnant or breastfeeding
* Significant cardiovascular diseases within the past 6 months including uncontrolled congestive heart failure (\> New York Heart Association \[NYHA\] class II), myocardial infarction, unstable angina, or uncontrolled arrhythmia
* History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine
* History or presence of clinically relevant non-lymphoma central nervous system pathology, including seizures that are uncontrolled on anticonvulsant therapy (\>= 1 seizure in the last year), paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson disease, cerebellar disease, or psychosis
* Treatment with any investigational agent on a different clinical trial within 4 weeks prior to enrollment, unless the patient is documented to be unresponsive to the therapy and at least 3 half-lives have elapsed prior to enrollment
* Treatment with any anti-CD19 or anti-CD20 antibody or antibody-drug conjugate therapy within 4 weeks before enrollment
* Previous treatment with CD19-targeted CAR T cells that has resulted in ongoing B cell aplasia at the time of enrollment; patients that demonstrate recovery of normal B cells (\>= 20 B cells/ul) by flow cytometry at any point 28 days or later after CD19 CAR T cell infusion will be considered to have functional loss of CD19 CAR T cells and are potentially eligible
* Patients with systemic disease without radiologic evidence of CNS involvement and with isolated CSF involvement detectable by flow cytometry are eligible for enrollment in systemic disease cohorts if neurologically asymptomatic. CSF involvement is not an exclusion for patients enrolled as a primary or secondary CNS lymphoma.
* Presence of active acute or chronic graft versus host disease (GVHD)
* Uncontrolled active infection (bacterial, fungal, viral, mycobacterial) not responding to treatment with intravenous antibiotics, antiviral or antifungal agents
* Patients with concurrent known additional malignancy that is progressing and/or requires active treatment; exceptions include squamous or basal cell carcinoma of the skin and low grade prostate carcinoma (Gleason grade =\< 6). Maintenance anti-hormone therapies for breast or prostate cancers are allowed and are not considered active treatment
* Patients with blood or platelet transfusion within 1 week prior to signing Consent A, or with platelets \< 50,000/mm\^3, neutrophils \< 750/mm\^3, or hemoglobin \< 8.5 g/dL, unless the cytopenias are considered by the treating physician to be largely due to marrow involvement by lymphoma

Answer: C