Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Phase I/II Study of Cellular Immunotherapy With Donor Central Memory-derived Virus-specific CD8+ T-cells Engineered to Target CD19 for CD19+ Malignancies After Allogeneic Hematopoietic Stem Cell Transplant
Brief Summary: This phase I/II trial studies the safety and toxicity of post-transplant treatment with donor T cells engineered to express a chimeric antigen receptor (CAR) targeting CD19 in patients who have had a matched related allogeneic hematopoietic stem cell transplant for a CD19+ B cell malignancy.


Options:
A: Inclusion Criteria:

* Confirmed DLBCL per local histopathology assessment.
* Relapsed or refractory disease after having recieved 2 or more lines of systemic therapy, including anti-CD20 and anthracycline based chemotherapy, and either having progressed after (or relapsed after) ASCT, or being not candidates for or not consenting to ASCT.
* Measurable disease at time of enrollment
* ECOG performance status that is either 0 or 1 at screening.

Exclusion Criteria:

* Patients with Richter's transformation, and Burkitt lymphoma, and primary DLBCL of CNS.
* Prior treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy.
* Patients with active CNS involvement are excluded, except if the CNS involvement has been effectively treated and provided that local treatment was \>4 weeks before enrollment.
* Prior allogeneic HSCT.
* Unstable angina and/or myocardial infarction and/or coronary artery bypass graft (CABG), or stroke within 6 months prior to screening, and/or impaired cardiac function or clinically significant cardiac disease
* Patients with a history of prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibodies, other immune checkpoint inhibitors.
* History of interstitial lung disease or (non-infectious) pneumonitis that required oral or intravenous steroids (other than COPD exacerbation) or current pneumonitis.

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: Inclusion Criteria:

1. Subject is ≥ 18 years and ≤ 75 years of age at the time of signing the informed consent form (ICF).
2. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1.
3. 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. Enough tumor material must be available for confirmation by central pathology.
4. Refractory or relapsed within 12 months from CD20 antibody and anthracycline containing first line therapy.
5. \[18F\] fluorodeoxyglucose (FDG) positron emission tomography (PET) positive lesion at screening. (Deauville score 4 or 5)
6. Adequate organ function
7. Participants must agree to use effective contraception

Exclusion Criteria:

1. Subjects not eligible for hematopoietic stem cell transplantation (HSCT).
2. Subjects planned to undergo allogeneic stem cell transplantation.
3. 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).
4. 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
5. Treatment with any prior gene therapy product.
6. Subjects who have received previous CD19-targeted therapy.
7. 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.
8. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection (including tuberculosis) despite appropriate antibiotics or other treatment.
9. Active autoimmune disease requiring immunosuppressive therapy.
10. 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.
11. History or presence of clinically relevant central nervous system (CNS) pathology
12. Pregnant or nursing (lactating) women.
D: Inclusion Criteria:

* Research participants enrolled are patients with an indication to be considered for HSCT, who are diagnosed with intermediate grade B-cell NHL (e.g., DLBCL, MCL or transformed NHL), and that have either recurrence/progression following prior therapy, or verification of high-risk disease in first remission
* Karnofsky performance status of \>= 70% and a life expectancy \>= 16 weeks at time of enrollment
* Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
* City of Hope (COH) pathology review confirms that research participant's diagnostic material is consistent with the history of intermediate grade B-cell NHL (e.g., DLBCL, MCL or transformed NHL)
* Negative serum pregnancy test for women of childbearing potential
* Research participant has an indication to be considered for autologous stem cell transplantation
* All patients must have the ability to understand and the willingness to sign a written informed consent

ELIGIBILITY TO UNDERGO AUTOLOGOUS MYELOABLATIVE TRANSPLANTATION WITH HEMATOPOETIC PROGENITOR CELL (HPC)A RESCUE

* Research participant meets all standard clinical parameters for candidates of autologous transplant as described in the current COH Hematopoietic Cell Transplant Standard Operating Policies, Procedures and Protocols
* Patient Evaluation \& Selection or Deferral for hematopoietic cell transplantation (HCT)
* Research participant is scheduled to receive a standard chemotherapy-based conditioning regimen, such as cyclophosphamide, carmustine, etoposide (CBV) or carmustine, etoposide, cytarabine, melphalan (BEAM)
* Research participant has a cryopreserved unselected HPCA product of at least 3 x 10\^6/kg CD34+ cells
* Research participant does not have evidence of disease progression after salvage therapy

ELIGIBILITY CRITERIA AT TIME OF INFUSION OF GENETICALLY MODIFIED AUTOLOGOUS T CELLS

* Research participant has a released cryopreserved T cell product
* Research participant has undergone an autologous HPC(A) procedure
* Not requiring supplemental oxygen or mechanical ventilation, oxygen saturation of 90% or higher on room air
* Not requiring pressor support, not having symptomatic cardiac arrhythmias
* Lack of acute renal failure/requirement for dialysis, as evidenced by creatinine \< 1.6 - Total bilirubin =\< 5.0
* Research participant without clinically significant encephalopathy/new focal deficits
* No clinical evidence of uncontrolled active infections process

Exclusion Criteria:

* Research participants with any uncontrolled illness including ongoing or active infection; research participants with known active hepatitis B or C infection; research participants who are human immunodeficiency virus (HIV) seropositive based on testing performed within 4 weeks of enrollment; research participants with any signs of symptoms of active infection, positive blood cultures or radiological evidence of infections
* Research participants receiving any other investigational agents, or concurrent biological, chemotherapy or radiation therapy
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to cetuximab
* Research participants with known brain metastases (central nervous system \[CNS\] involvement or parenchymal or leptomeningeal involvement)
* Research participants with presence of other malignancy or history of prior malignancy within 5 years of study entry; although patients treated with curative intent within 5 year are eligible; this exclusion rule does not apply to non-melanoma skin tumors and in-situ cervical cancer
* Failure of research participant to understand the basic elements of the protocol and/or the risks/benefits of participating in this phase I/II study; a legal guardian may substitute for the research participant
* History of allogeneic HSCT or prior autologous HSCT
* Any standard contraindications to myeloablative HSCT per standard of care practices at COH
* Dependence on corticosteroids
* Active autoimmune disease requiring systemic immunosuppressive therapy
* Research participants will be excluded, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Answer: B