Tisagenlecleucel in Adult Patients With Aggressive B-cell Non-Hodgkin Lymphoma
a study on Hodgkin's Lymphoma Lymphoma Non-Hodgkin Lymphoma
Summary
- Eligibility
- for people ages 18 years and up (full criteria)
- Location
- at La Jolla, California and other locations
- Dates
- study startedestimated completion
Description
Summary
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.
Official Title
Tisagenlecleucel Versus Standard of Care in Adult Patients With Relapsed or Refractory Aggressive B-cell Non-Hodgkin Lymphoma: A Randomized, Open Label, Phase III Trial (BELINDA)
Keywords
Non-Hodgkin Lymphoma, Non-Hodgkin's Lympoma, B-Cell Lymphoma, Diffuse Large B-cell Lymphoma, High Grade B-cell Lymphoma, Follicular Lymphoma grade 3B, CAR-T, Tisagenlecleucel, Kymriah, Immunotherapy, Cellular therapy, CTL019, Lymphoma, Tisagenlecleucel after optional bridging and lymphodepleting chemotherapy, Platinum-based immunochemotherapy followed in responding patients with high dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT)
Eligibility
You can join if…
Open to people ages 18 years and up
- 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):
- 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 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.
You CAN'T join if...
- 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 crediblemeds.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))
Other protocol-defined inclusion and exclusion criteria may apply.
Locations
- Moores UC San Diego Cancer Center
La Jolla California 92093 United States - University of California Los Angeles University of California LA
Los Angeles California 90095 United States
Details
- Status
- in progress, not accepting new patients
- Start Date
- Completion Date
- (estimated)
- Sponsor
- Novartis Pharmaceuticals
- ID
- NCT03570892
- Phase
- Phase 3 research study
- Study Type
- Interventional
- Participants
- About 331 people participating
- Last Updated