BELINDA: This phase III trial is comparing an immunotherapy to standard of care treatment in adults who have been diagnosed with B-cell Non-Hodgkin Lymphoma and have failed prior immunochemotherapyTisagenlecleucel Versus Standard of Care in Adult Patients With Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma: A Randomized, Open Label, Phase III Trial

Inclusion

1. Histologically confirmed, aggressive B-cell NHL at relapse/progression or PR after front line therapy. Aggressive B-cell NHL is heretofore defined by the following list of subtypes (Swerdlow et al 2016):

   1. DLBCL, NOS,
   2. FL grade 3B,
   3. Primary mediastinal large B cell lymphoma (PMBCL),
   4. T cell rich/histiocyte rich large B cell lymphoma (T/HRBCL),
   5. DLBCL associated with chronic inflammation,
   6. Intravascular large B-cell lymphoma,
   7. ALK+ large B-cell lymphoma,
   8. B-cell lymphoma, unclassifiable, (with features intermediate between DLBCL and classical Hodgkin's Lymphoma (HL)),
   9. High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements,
   10. High-grade B-cell lymphoma, NOS
   11. HHV8+ DLBCL, NOS
   12. DLBCL transforming from follicular lymphoma
   13. DLBCL transforming from marginal zone lymphoma
   14. DLBCL, leg type
2. Relapse or progression within 365 days from last dose of anti CD20 antibody and anthracycline containing first line immunochemotherapy or refractory (have not achieved a CR).
3. Patient is considered eligible for autologous HSCT as per local investigator assessment. Note: Intention to transplant and type of high dose chemotherapy (HDCT) regimen will be documented at the time of study entry

4. Disease that is both active on PET scan (defined as 5-Deauville scorepoint-scale of 4 or 5) and measurable on CT scan, defined as::

   1. Nodal lesions >15 mm in the long axis, regardless of the length of the short axis, and/or
   2. Extranodal lesions (outside lymph node or nodal mass, but including liver and spleen) >10 mm in long AND short axis
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1

6. Adequate organ function:

   Renal function defined as:

   1. Serum creatinine of ≤1.5 x upper limit of normal (ULN), OR estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2

      Hepatic function defined as:

   2. Alanine Transaminase (ALT) and Aspartate Transiminase (AST) ≤ 5 × ULN

   3. Total bilirubin ≤ 1.5 x ULN with the exception of patients with Gilbert syndrome who may be included if their total bilirubin is ≤3.0 × ULN and direct bilirubin ≤1.5 × ULN

      Hematologic Function (regardless of transfusions) defined as:

   4. Absolute neutrophil count (ANC) >1000/mm3
   5. Absolute lymphocyte count (ALC) >300/mm3 OR Absolute number of CD3+ T cells >150/mm3 (only for patients with non-historical apheresis)
   6. Platelets ≥50000/mm3

   7. Hemoglobin >8.0 g/dl

      Adequate pulmonary function defined as:

   8. No or mild dyspnea (≤ Grade 1)
   9. Oxygen saturation measured by pulse oximetry > 90% on room air
   10. Forced expiratory volume in 1 s (FEV1) ≥ 50% and/or carbon monoxide diffusion test (DLCO) ≥50% of predicted level
7. Must have a leukapheresis material of non-mobilized cells available for manufacturing.