Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase 2 Open-Label, Multicenter Study Evaluating the Safety and Efficacy of Axicabtagene Ciloleucel in Combination With Rituximab in Participants With Refractory Large B-Cell Lymphoma (ZUMA-14)
Brief Summary: The primary objective of this study is to estimate the efficacy of axicabtagene ciloleucel in combination with rituximab, as measured by assessment of response rates in adult participants with relapsed/refractory large B-cell lymphoma.


Options:
A: Key Inclusion Criteria:

* Histologically confirmed large B-cell lymphoma
* Chemotherapy-refractory disease, defined as one or more of the following:

  * No response to first-line therapy (primary refractory disease)
  * No response to second or greater lines of therapy OR
  * Refractory after autologous stem cell transplant (ASCT)
* At least 1 measureable lesion according to the Lugano Classification (Cheson 2014).
* Individuals must have received adequate prior therapy, including at a minimum:

  * Anti-CD20 monoclonal antibody
  * An anthracycline-containing chemotherapy regimen
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Adequate renal, hepatic, pulmonary, and cardiac function

Key Exclusion Criteria:

* Known CD19 negative or CD20 negative tumor
* History of Richter's transformation of Chronic Lymphocytic Leukemia (CLL)
* Prior CAR therapy or other genetically modified T-cell therapy
* Prior organ transplantation including prior allogeneic stem cell transplant (SCT)
* Prior CD19 targeted therapy
* Clinically significant infection or cardiopulmonary disease
* Presence of any in-dwelling lines or drains (dedicated central venous access catheters allowed)
* History or presence of central nervous system (CNS) lymphoma or nonmalignant CNS disorder or cerebrospinal fluid (CSF) malignant cells or brain metastases
* History of autoimmune disease
* History of deep vein thrombosis (DVT) or pulmonary embolism (PE) within the last 6 months

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

* Patients with CD19+ B cell malignancy who have persistent, relapsed or progressive disease after hematopoietic stem cell transplant from an human leukocyte antigen (HLA)-matched related donor OR patients with CD19+ B cell malignancy who are planned for or have had a hematopoietic stem cell transplant from an HLA-matched related donor and are at risk of relapse after HCT defined by any one of the disease-specific criteria listed below:

  * Philadelphia chromosome negative acute lymphoblastic leukemia:

    * Beyond first complete remission (CR) at the time of pre-transplant evaluation
    * Required \> 1 cycle of induction chemotherapy to achieve CR
    * First morphologic CR but with evidence of minimal residual disease by flow cytometry, conventional cytogenetics, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR)
    * First CR with poor risk cytogenetics (t(4:11), t(8;14), hypodiploidy, near triploidy or \> 5 cytogenetic abnormalities) at diagnosis
    * Planned for or have had a reduced intensity conditioned or non-myeloablative transplant
  * Philadelphia positive acute lymphoblastic leukemia

    * Not in CR at the time of pre-transplant evaluation
    * In CR with the following features:

      * Intolerant or unwilling to use a TKI after HCT
      * Current or previous detection of cytogenetic abnormalities in addition to t(9;22) by conventional karyotyping, FISH or molecular methods
  * Chronic lymphocytic leukemia, or low grade B cell lymphomas:

    * Failed or ineligible for prior immunochemotherapy that included a purine analog and anti-CD20 monoclonal antibody AND a lymph node \>= 5 cm at the time of pre-transplant evaluation
  * Mantle cell lymphoma:

    * Failed or ineligible for autologous transplant AND a lymph node \>= 2 cm at the time of pre-transplant evaluation
  * Diffuse large B cell lymphomas, large B cell transformation of an indolent lymphoma or other aggressive B cell lymphomas

    * Failed or ineligible for autologous transplant AND not in CR at the time of pre-transplant evaluation
* Confirmation of tumor diagnosis and expression of CD19 after review by University of Washington Medical Center (UWMC) or Seattle Cancer Care Alliance (SCCA) pathology services
* The patient has signed the informed consent form for this study
* DONOR: Genotypic or phenotypic HLA-identical family members
* DONOR: Express one or more of the following combinations of viral serostatus and HLA allele:

  * CMV seropositive and HLA-A\*0101 positive
  * CMV seropositive and HLA-A\*0201 positive
  * CMV seropositive and HLA-B\*0702 positive
  * CMV seropositive and HLA-B\*0801 positive
  * EBV seropositive and HLA-A\*0201 positive
  * EBV seropositive and HLA-B\*0801 positive
* DONOR: Hematocrit \>= 35% at enrollment
* DONOR: Age \>= 18 years
* DONOR: The donor has signed the informed consent form for the study

Exclusion Criteria:

* Known central nervous system (CNS) tumor (CNS2 or CNS3) that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; patients with a history of CNS disease that has been effectively treated to CNS1 or lower evidence of disease will be eligible
* Human immunodeficiency virus (HIV) seropositive
* Significant medical or psychological conditions that would make them unsuitable candidates for T cell therapy
* Fertile patients unwilling to use contraception during and for 12 months after protocol enrollment
* Pregnant or breast-feeding
* DONOR: G-CSF administered within one month prior to the blood draw for T cell collection
* DONOR: Unable for any reason to provide a 400 ml blood draw
* DONOR: Inadequate peripheral veins for blood collection
* DONOR: HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1 or HTLV-2 seropositive
* DONOR: Active hepatitis B or hepatitis C virus infection
* DONOR: Positive serologic test for syphilis
* DONOR: Aberrant CD45RA isoform expression on all T cells
* DONOR: Systolic blood pressure (BP) \< 80 or \> 200
* DONOR: Heart rate \< 50 or \> 120, if considered due to cardiac disease
* DONOR: Oxygen (O2) saturation \< 88% on room air
* DONOR: Serum creatinine (Cr) \> 3.0
* DONOR: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 4 x the upper limit of normal
* DONOR: Unable to provide informed consent to participate
* DONOR: Significant medical conditions (e.g. immunosuppressive therapy) that would make them unsuitable T cell donors
* DONOR: Pregnant or nursing
C: 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.
D: Inclusion Criteria:

* RECIPIENT: Patients with high risk or relapsed disease who are planning to receive, or have received prior allogeneic HSCT from an human leukocyte antigen (HLA)-matched related, or HLA-mismatched related donor; high risk is defined as patients with acute lymphoblastic leukemia who have delayed clearance of minimal residual disease, Philadelphia (Ph)-like, or complex, 11q23 or hypodiploid karyotype
* RECIPIENT: Available donor who provided hematopoietic stem-cell (HSC)
* RECIPIENT: Patients with CD19+ lymphoid malignancies that are refractory to or intolerant of standard treatment (as defined below):

  * B-cell Acute Lymphoblastic Leukemia (ALL)
  * Non-Hodgkin lymphoma (NHL) to include diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B cell lymphoma, mantle cell lymphoma, or transformed follicular lymphoma (TFL) as defined by the World Health Organization 2008 criteria
  * Small lymphocytic lymphoma (SLL)
  * Chronic lymphocytic leukemia (CLL)
  * NOTE: Refractory disease for acute and chronic leukemia is defined by:

    * Presence of \> 5% malignant blasts in bone marrow and/or peripheral blood and/or minimal residual disease by flow cytometry or molecular analysis for fusion proteins and/or positive imaging for extra-medullary disease to most recent therapy
  * NOTE: Refractory disease for lymphoma is defined as:

    * Progressive disease or stable disease lasting =\< 6 months, as best response to most recent chemotherapy regimen; or disease progression or recurrence =\< 12 months after prior ASCT
    * Prior therapy must have included an anti-CD20 monoclonal antibody-containing regimen and an anthracycline-containing chemotherapy regimen
    * For patients with TFL, prior chemotherapy for follicular lymphoma and subsequent refractory disease after transformation to DLBCL
    * At least one measurable lesion according to revised International Working Group (IWG) Response Criteria
* RECIPIENT: In patients with prior transplant, treatment will begin no earlier than 3 months post-transplant. Enrollment can occur earlier to allow time for donor cell collection
* RECIPIENT: Karnofsky performance scale \> 60
* RECIPIENT: Patient able to provide written informed consent
* RECIPIENT: Patient able to provide written informed consent for the long-term follow-up (LTFU) gene therapy study
* RECIPIENT: Negative human anti-mouse antibody (HAMA)
* DONOR: HLA-matched related, HLA-mismatched related, including haploidentical donor, or related donor cleared to donate based on Stem Cell Transplantation and Cellular Therapy (SCTCT) standard-of-care (SOC) guidelines
* DONOR: Negative beta HCG in female of child-bearing potential defined as:

  * Not post-menopausal for 12 months, or
  * No previous surgical sterilization, or
  * Lactating females
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: Patient must have measurable disease at the time of treatment
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: Not received anti-thymocyte globulin (ATG), Campath, or other T-cell immunosuppressive antibodies or donor-lymphocyte infusion in the 28 days prior to T-cell infusion
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: Serum creatinine \< 2 x upper limit of normal (ULN)
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) =\< 2.5 x ULN or =\< 5 x ULN if documented liver metastases
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: Total bilirubin =\< 1.5 mg/dL, except in patients with Gilbert's syndrome in whom total bilirubin must be =\< 3.0 mg/dL
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: Cardiac ejection fraction \>= 40%, and no clinically-significant electrocardiogram (ECG) findings
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: No clinically significant pleural effusion, baseline oxygen saturation \> 90% on room air
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: No evidence of grade \>= 2 active graft versus host disease (GVHD) using the Center for International Blood and Marrow Transplant Research (CIBMTR) Acute GVHD Grading System or requiring systemic steroid therapy greater than physiologic dosing at time of starting treatment
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: Non-hematologic toxicity grade \>= 2 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5) related to the lymphodepleting chemotherapy until the toxicity has resolved to grade =\< 1 and the patient is afebrile
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: No new grade \> 2 neurologic, pulmonary, cardiac, gastrointestinal, renal or hepatic (excluding albumin) toxicity
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: Serum creatinine \< 2 x ULN
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: Oxygen saturation \> 90% on room air
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: Active clinically significant infection within 7-days of study treatment
* T-CELL INFUSION REQUIREMENTS FOR RECIPIENT: Using an investigational agent

Exclusion Criteria:

* RECIPIENT: Positive beta human chorionic gonadotropin (HCG) in female of child-bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization or lactating females
* RECIPIENT: Patients with allergy to mouse products or cetuximab
* RECIPIENT: Active central nervous system (CNS) disease in patient with history of CNS malignancy
* RECIPIENT: Positive serology for human immunodeficiency virus (HIV)
* RECIPIENT: Active hepatitis B or active hepatitis C
* RECIPIENT: Has received a T-cell product within 6 weeks prior to planned infusion of genetically modified T cells

Answer: A