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Tisagenlecleucel in Adult Patients With Aggressive B-cell Non-Hodgkin Lymphoma

Trial Status: Active

This is a randomized, open label, multicenter phase III trial comparing the efficacy, safety, and tolerability of tisagenlecleucel to Standard Of Care in adult patients with aggressive B-cell Non-Hodgkin Lymphoma after failure of rituximab and anthracycline containing frontline immunochemotherapy.

Inclusion Criteria

  • 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):
  • FL grade 3B,
  • Primary mediastinal large B cell lymphoma (PMBCL),
  • T cell rich/histiocyte rich large B cell lymphoma (T/HRBCL),
  • DLBCL associated with chronic inflammation,
  • Intravascular large B-cell lymphoma,
  • ALK+ large B-cell lymphoma,
  • B-cell lymphoma, unclassifiable, (with features intermediate between DLBCL and classical Hodgkin's Lymphoma (HL)),
  • High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements,
  • High-grade B-cell lymphoma, NOS
  • DLBCL transforming from follicular lymphoma
  • DLBCL transforming from marginal zone lymphoma
  • DLBCL, leg type
  • 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).
  • 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
  • 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::
  • Nodal lesions >15 mm in the long axis, regardless of the length of the short axis, and/or
  • Extranodal lesions (outside lymph node or nodal mass, but including liver and spleen) >10 mm in long AND short axis
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Adequate organ function: Renal function defined as:
  • 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:
  • Alanine Transaminase (ALT) and Aspartate Transiminase (AST) ≤ 5 × ULN
  • 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:
  • Absolute neutrophil count (ANC) >1000/mm3
  • Absolute lymphocyte count (ALC) >300/mm3 OR Absolute number of CD3+ T cells >150/mm3 (only for patients with non-historical apheresis)
  • Platelets ≥50000/mm3
  • Hemoglobin >8.0 g/dl Adequate pulmonary function defined as:
  • No or mild dyspnea (≤ Grade 1)
  • Oxygen saturation measured by pulse oximetry > 90% on room air
  • Forced expiratory volume in 1 s (FEV1) ≥ 50% and/or carbon monoxide diffusion test (DLCO) ≥50% of predicted level
  • Must have a leukapheresis material of non-mobilized cells available for manufacturing.

Exclusion Criteria

  • Prior treatment with anti-CD19 therapy, T cell therapy, or any prior gene therapy product
  • Treatment with any systemic lymphoma-directed second line anticancer therapy prior to randomization. Only steroids and local irradiation are permitted for disease control
  • Patients with active central nervous system (CNS) involvement by disease under study are excluded, except if the CNS involvement has been effectively treated and local treatment was >4 weeks before randomization
  • Prior allogeneic HSCT
  • Clinically significant active infection
  • Any of the following cardiovascular conditions:
  • Unstable angina, myocardial infarction, coronary artery bypass graft (CABG), or stroke within 6 months prior to screening,
  • Left ventricle ejection fraction (LVEF) <45% as determined by echocardiogram (ECHO) or magnetic resonance angiography (MRA) or multigated acquisition (MUGA) at the screening assessment.
  • New York Heart Association (NYHA) functional class III or IV (Chavey et al 2001), within the past 12 months.
  • Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), complete left bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicular block, Mobitz type II) and third degree AV block unless adequately controlled by pacemaker implantation.
  • Resting QTcF ≥450 msec (male) or ≥460 msec (female) at screening or inability to determine the QTcF interval
  • Risk factors for Torsades de Pointes (TdP), including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/ symptomatic bradycardia, or any of the following:
  • Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome
  • Concomitant medication(s) with a "Known Risk of Torsades de Pointes" per that cannot be discontinued or replaced by safe alternative medication.
  • Patients with active neurological autoimmune or inflammatory disorders (e.g., Guillain-Barré Syndrome (GBS), Amyotrophic Lateral Sclerosis (ALS)) and clinically significant active cerebrovascular disorders (e.g. cerebral edema, posterior reversible encephalopathy syndrome (PRES))


Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Contact: Steven Singer
Phone: 310-825-4477
San Diego
University of California San Diego
Status: ACTIVE
San Francisco
UCSF Medical Center-Mount Zion
Status: ACTIVE
Contact: UCSF Clinical Trials
Phone: 877-827-3222


Emory University Hospital / Winship Cancer Institute
Status: ACTIVE


University of Chicago Comprehensive Cancer Center
Status: ACTIVE


Kansas City
University of Kansas Cancer Center
Status: ACTIVE
Contact: Dana Wheeler
Phone: 913-945-7550


Wayne State University / Karmanos Cancer Institute
Status: ACTIVE


University of Nebraska Medical Center
Status: ACTIVE

North Carolina

Duke University Medical Center
Status: ACTIVE


Ohio State University Comprehensive Cancer Center
Status: ACTIVE


OHSU Knight Cancer Institute


University of Pennsylvania / Abramson Cancer Center
Status: ACTIVE

South Carolina

Medical University of South Carolina
Status: ACTIVE


M D Anderson Cancer Center
Status: ACTIVE


University of Wisconsin Hospital and Clinics
Status: ACTIVE

Trial Phase Phase III

Trial Type Treatment

Lead Organization
Novartis Pharmaceuticals Corporation

  • Primary ID CCTL019H2301
  • Secondary IDs NCI-2018-02925, 2016-002966-29
  • ID NCT03570892