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

Status: Active

Description

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.

Eligibility Criteria

Inclusion Criteria

  • Histologically confirmed, aggressive B-cell NHL at relapse/progression after front line therapy. Aggressive B-cell NHL is heretofore defined by the following list of subtypes (Swerdlow et al 2016):
  • DLBCL, NOS,
  • 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
  • HHV8+ DLBCL, 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 rituximab and anthracycline containing first line immunochemotherapy or refractory (have not achieved a CR or PR).
  • 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
  • Measurable disease: a. Nodal lesions >15 mm in the long axis, regardless of the length of the short axis, and/or b. 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
  • Absolute number of CD3+ T cells >150/mm3
  • Platelets ≥50000/mm3
  • Hemoglobin >8.0 g/dl

Exclusion Criteria

  • Prior treatment with anti-CD19 therapy, T cell therapy, or any prior gene therapy product
  • Treatment with any lymphoma-directed second line anticancer therapy prior to randomization. Only steroids 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 (i.e. patient is asymptomatic) and local treatment was >4 weeks before randomization
  • Prior allogeneic HSCT 4. Clinically significant active infection 5. 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 www.qtdrugs.org 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))

Locations & Contacts

California

San Francisco
UCSF Medical Center-Mount Zion
Status: Active
Contact: UCSF Clinical Trials
Phone: 877-827-3222
Email: cancertrials@ucsf.edu

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Approved
Name Not Available

Illinois

Chicago
University of Chicago Comprehensive Cancer Center
Status: Active
Name Not Available

Michigan

Detroit
Wayne State University / Karmanos Cancer Institute
Status: Active
Name Not Available

Nebraska

Omaha
University of Nebraska Medical Center
Status: Active
Name Not Available

Ohio

Columbus
Ohio State University Comprehensive Cancer Center
Status: In review
Name Not Available

Oregon

Portland
OHSU Knight Cancer Institute
Status: Active
Name Not Available

Pennsylvania

Philadelphia
University of Pennsylvania / Abramson Cancer Center
Status: Active
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase III

Trial Type

Treatment

Lead Organization

Lead Organization
Novartis Pharmaceuticals Corporation

Trial IDs

Primary ID CCTL019H2301
Secondary IDs NCI-2018-02925, 2016-002966-29
Clinicaltrials.gov ID NCT03570892