Please select the eligibility criteria that correspond to the clinical trial below.
Title: Donor-Derived Very-Rapid Manufactured CD19-Specific T Cells for Lymphoid Malignancies After Allogeneic Hematopoietic Stem-Cell Transplantation
Brief Summary: This phase I trial investigates the side effects and best dose of CD19 positive (+) specific CAR-T cells in treating patients with CD19+ lymphoid malignancies, such as acute lymphoblastic leukemia, non-Hodgkin lymphoma, small lymphocytic lymphoma, or chronic lymphocytic lymphoma. Sometimes researchers change the genetic material in the cells of a patient's T cells using a process called gene transfer. Researchers then inject the changed T-cells into the patient's body. Receiving the T-cell infusion may help to control the disease.


Options:
A: Inclusion Criteria:

* Subjects must meet all of the following criteria to be enrolled in this study:

  1. Age ≥ 18 years at the time of consent
  2. Signed written informed consent obtained prior to any study procedures
  3. Relapsed or refractory B-cell NHL.
  4. PET-positive disease BY Lugano classification
  5. 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.
  6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  7. Adequate bone marrow, renal, hepatic, pulmonary and cardiac function
  8. Adequate vascular access for leukapheresis procedure
  9. Subjects who have received previous CD19-targeted therapy must have CD19-positive lymphoma confirmed on a biopsy since completing the prior CD19-targeted therapy
  10. Subjects must agree to use appropriate contraception.

Exclusion Criteria:

* Subjects who meet any of the following criteria will be excluded from participation in this study:

  1. Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study)
  2. History of another primary malignancy that has not been in remission for at least 2 years.
  3. Treatment with alemtuzumab within 6 months of leukapheresis, or treatment with fludarabine or cladribine within 3 months of leukapheresis
  4. Active hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) infection at the time of screening
  5. Subjects with uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis or JWCAR029 administration
  6. Presence of acute or chronic graft-versus-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. Prior CAR T-cell or other genetically-modified T-cell therapy, with the exception of prior JWCAR029 treatment in this protocol for subjects receiving retreatment
B: Inclusion Criteria:

1. Male or female, aged ≥18 years.
2. Willing and able to give written, informed consent.
3. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 1.
4. Histologically confirmed DLBCL and large B cell lymphoma (at last relapse) subsets, including:

   Phase I and Phase II Cohort 1:
   1. DLBCL, not otherwise specified (NOS), per World Health Organisation classification and DLBCL with MYC and BCL2 and/or BCL6 rearrangements (double/triple hit).
   2. Transformed DLBCL from FL.
   3. High-grade B cell lymphoma with MYC expression (excluding Burkitt's lymphoma)

      Phase I and Phase II Cohort 2:
   4. Transformed DLBCL from other indolent lymphomas (excluding Richter's transformation).
   5. Primary mediastinal large B cell lymphoma.
5. Chemotherapy-refractory disease, defined as one or more of the following:

   1. Stable disease (≤12 months) or progressive disease as best response to most recent chemotherapy containing regimen. Refractory disease after frontline chemo-immunotherapy is allowed.
   2. Disease progression or recurrence in ≤12 months of prior autologous haematopoietic stem cells transplantation (ASCT).

   OR
6. Relapse after ≥two lines of therapy or after ASCT. At a minimum:

   1. Patients must have received rituximab or another anti-CD20 monoclonal antibody (unless Investigator determines that tumour is CD20-negative) and an anthracycline-containing chemotherapy regimen.
   2. Patients must have either failed ASCT, or be ineligible for or not consenting to ASCT.
   3. Patients with transformed DLBCL must have received at least one line of therapy after transformation to DLBCL.
7. PET-positive disease per Lugano classification.
8. For females of childbearing potential, a negative serum or urine pregnancy test must be documented at screening, prior to pre-conditioning and confirmed before receiving the first dose of study treatment.

   For females who are not postmenopausal or surgically sterile, highly effective methods of contraception must be used during the treatment period and for at least 12 months after the last dose of study treatment.
9. For males, it must be agreed that that two acceptable methods of contraception are used.
10. Adequate renal, hepatic, pulmonary, and cardiac function defined as:

    1. Creatinine clearance ≥40 cc/min.
    2. Serum alanine aminotransferase / aspartate aminotransferase ≤2.5 x ULN.
    3. Total bilirubin ≤1.5 x ULN, except in subjects with Gilbert's syndrome.
    4. LVEF ≥50% (by ECHO or MUGA) unless the institutional lower limit of normal is lower.
    5. Baseline oxygen saturation \>92% on room air and ≤Grade 1 dyspnoea.
11. Patient has adequate BM function without requiring ongoing blood product or granulocyte-colony stimulating factor support and meets the following criteria:

    1. Absolute neutrophil count ≥1.0 × 109/L.
    2. Absolute lymphocyte count ≥0.3 × 109/L (at enrolment and prior to leukapheresis).
    3. Haemoglobin ≥80 g/L.
    4. Platelets ≥75 × 109/L
12. No contra-indications for leukapheresis.

Exclusion Criteria:

1. Prior allogeneic haematopoietic stem cell transplant.
2. Females who are pregnant or lactating.
3. History or presence of clinically relevant CNS pathology such as epilepsy, paresis, aphasia, stroke within prior 3 months, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, uncontrolled mental illness, or psychosis.
4. Patients with active CNS involvement by malignancy. Patients with history of CNS involvement with malignancy may be eligible if CNS disease has been effectively treated and provided treatment was at least 4 weeks prior to enrolment (at least 8 weeks prior to AUTO3 infusion).
5. Clinically significant, uncontrolled heart disease or a recent (within 12 months) cardiac event.

   1. Uncontrolled cardiac arrhythmia (patients with rate-controlled atrial fibrillation are not excluded).
   2. Evidence of pericardial effusion
6. Patients with a history (within 3 months) or evidence of deep vein thrombosis or pulmonary embolism requiring ongoing therapeutic anticoagulation at the time of pre-conditioning.
7. Patients with active gastrointestinal bleeding.
8. Patients with any major surgical intervention in the last 3 months.
9. Active bacterial, viral or fungal infection requiring systemic treatment. Active or latent hepatitis B infection or hepatitis C infection. Testing positive for human immunodeficiency virus, human T cell lymphotropic virus (HTLV1 and 2) or syphilis.
10. History of autoimmune disease resulting in end organ injury or requiring systemic immunosuppression/systemic disease modifying agents within the last 24 months.
11. Patients with a known history or prior diagnosis of optic neuritis or other immunologic or inflammatory disease affecting the CNS.
12. Evidence of active pneumonitis on chest computed tomography (CT) scan at screening or history of drug-induced pneumonitis, idiopathic pulmonary fibrosis, organising pneumonia, or idiopathic pneumonitis.
13. History of other malignant neoplasms unless disease free for at least 24 months (carcinoma in situ, non-melanoma skin cancer, breast or prostate cancer on hormonal therapy allowed).
14. Prior treatment with PD1, PD-L1, or cytotoxic T lymphocyte-associated protein-4-targeted therapy, or tumour necrosis factor (TNF) receptor superfamily agonists within 6 weeks prior to AUTO3 infusion.
15. Prior treatment with investigational or approved gene therapy or cell therapy products until a dose level has treated at least three patients and has been declared safe.
16. Prior CD19 or CD22 targeted therapy.
17. The following medications are excluded:

    1. Steroids: Therapeutic doses of corticosteroids within 7 days of leukapheresis or 72 hours prior to AUTO3 administration. However, physiological replacement, topical, and inhaled steroids are permitted.
    2. Immunosuppression: Immunosuppressive medication must be stopped ≥2 weeks prior to leukapheresis or AUTO3 infusion.
    3. Cytotoxic chemotherapies within 2 weeks of AUTO3 infusion and 1 week prior to leukapheresis (2 weeks for lymphodepleting chemotherapy).
    4. Antibody therapy use including anti-CD20 therapy within 2 weeks prior to AUTO3 infusion, or 5 half-lives of the respective antibody, whichever is shorter.
    5. Granulocyte-colony stimulating factor less than 10 days prior to leukapheresis.
    6. Live vaccine ≤4 weeks prior to enrolment.
    7. Prophylactic intrathecal therapy: Methotrexate within 4 weeks and other intrathecal chemotherapy (e.g. Ara-C) within 2 weeks prior to starting pre-conditioning chemotherapy.
18. Prior limited radiation therapy within 4 weeks of AUTO3 infusion or within 24 weeks for definitive radiation to chest.
19. Research participants receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy.
20. Known allergy to albumin, dimethyl sulphoxide (DMSO), cyclophosphamide or fludarabine, pembrolizumab or tocilizumab.
21. Any contraindications to receive anti-PD1 antibody pembrolizumab will be excluded from cohorts requiring administration of pembrolizumab.
22. Patients, who in the opinion of the Investigator, may not be able to understand or comply with the safety monitoring requirements of the study.
23. Any other condition that in the Investigator's opinion would make the patient unsuitable for the clinical trial.

    Phase I outpatient cohort:
24. Subjects who do not have caregiver support (in line with institutional outpatient transplant guidelines) for outpatient/ambulatory care setting.
25. Subjects who are staying greater than 60 minutes (or whatever is permissible per institutional outpatient transplant guidelines) from the clinical trial site at the time of treatment.

For AUTO3 Infusion: Patients meeting any of the following exclusion criteria must not be treated with AUTO3 or have treatment delayed until they no longer meet these criteria:

1. Severe intercurrent infection.
2. Requirement for supplementary oxygen or active pulmonary infiltrates.
3. Clinical deterioration of organ function (renal and hepatic) exceeding the criteria set at study entry.
C: 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
D: Inclusion Criteria:

1. 18 Years to 70 Years, Male and female;
2. Expected survival \> 12 weeks;
3. Performance score 0-2;
4. Histologically confirmed as CD19-positive lymphoma and who meet one of the following conditions;

   * Patient receive at least 2-4 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment;
   * Disease recurrence after stem cell transplantation;
   * Diagnosis as lymphoma, but refuse conventional treatment such as chemotherapy, radiation, stem cell transplantation and monoclonal antibody therapy
5. Creatinine \< 2.5 mg/dl;
6. ALT/AST \< 3x normal;
7. Bilirubin \< 2.0 mg/dl;
8. Adequate venous access for apheresis, and no other contraindications for leukapheresis;
9. Take contraceptive measures before recruit to this trial;
10. Written voluntary informed consent is given.

Exclusion Criteria:

1. Patients with symptoms of central nervous system
2. Accompanied by other malignant tumor
3. Active hepatitis B or C, HIV infection
4. Any other diseases could affect the outcome of this trial
5. Suffering severe cardiovascular or respiratory disease
6. Poorly controlled hypertension
7. A history of mental illness and poorly controlled
8. Taking immunosuppressive agents within 1 week due to organ transplantation or other disease which need long-lasting administration
9. Occurrence of unstable pulmonary embolism, deep vein thrombosis, or other major arterial/venous thromboembolic events 30 days prior to assignment
10. Reaching a steady dose if receiving anticoagulant therapy before assignment
11. Female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion
12. Pregnant or lactating women
13. Subject suffering disease affects the understanding of informed consent or comply with study protocol.

Answer: C