Tisagenlecleucel in Adult Patients With Aggressive B-cell Non-Hodgkin Lymphoma
Hematopoietic Malignancies
Lymphoma
Non-Hodgkin Lymphoma
Unknown Primary
18 Years and older, Male and Female
CCTL019H2301 (primary)
NCI-2018-02925
2016-002966-29
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.
Objectives
Approximately 318 subjects were planned to be randomized; 322 subjects were analyzed
(Full analysis set): 162 subjects in the tisagenlecleucel arm and 160 subjects in the SOC
arm.
The target population consisted of adult participants with aggressive B-cell non-Hodgkin
lymphoma (NHL) who were relapsed/refractory within 365 days of their last dose of first
line immunochemotherapy and eligible for autologous hematopoietic stem cell
transplantation (HSCT).
The duration of treatment in the tisagenlecleucel treatment strategy is from the start of
bridging chemotherapy (if applicable) until the infusion of tisagenlecleucel (expected on
average at approximately 6 weeks from randomization). The duration of the treatment in
the SOC treatment strategy is from the start of salvage chemotherapy until autologous
HSCT. In either treatment arm, if infusion of tisagenlecleucel or autologous HSCT is not
possible, the duration of treatment is until the last dose of study treatment prior to
discontinuation of the treatment strategy.
Eligibility
- 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.
Treatment Sites in Georgia
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