CTIS2023-508343-48-00RecruitingPhase 1
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) - CCTL019H2301
Conditions
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- ovartis Pharma AG
- Enrollment
- 348
Study Overview
Brief Summary
No summary available.
Study Design
- Study Type
- Interventional
Eligibility Criteria
- Ages
- 18 to 65+ (—)
- Sex
- All
Inclusion Criteria
- •Signed informed consent must be obtained prior to participation in the study., Patients must be =18 years of age at the time of informed consent form (ICF) signature., Histologically confirmed (by local histopathological assessment), aggressive B-cell NHL at relapse/progression or PR after front line therapy. For patients with relapse/progression if biopsy after relapse/progression is not available or not clinically feasible to obtain a new biopsy, an archival tumor biopsy from the initial diagnosis may be submitted. For patients in PR after at least 6 cycles of first line treatment, a new biopsy must be submitted. 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 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 in the IRT system at the time of study entry, Disease that is both active on PET scan (defined as Deauville score 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: a. 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 b. Hepatic function defined as: - Alanine Transaminase (ALT) and Aspartate Transaminase (AST) = 5 × ULN - Total Bilirubin =1.5 × 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 c. Hematologic Function (regardless of transfusions) defined as: - Absolute neutrophil count (ANC) >1000/mm3 - Platelets =50,000/mm3 - Hemoglobin >8.0 g/dl Only for patients with non-historical apheresis: - Absolute lymphocyte count (ALC) >300/mm3 or - Absolute number of CD3+ T cells >150/mm3 d. 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% or carbon monoxide diffusion test (DLCO) =50% of predicted level, Must have a leukapheresis material of non-mobilized cells available for manufacturing
Exclusion Criteria
- •Epstein Barr Virus positive (EBV+) DLBCL, NOS, Richter’s transformation, and Burkitt lymphoma, and primary DLBCL of CNS., 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, Investigational medicinal product (IMP) within the last 30 days prior to screening. Note: IMPs should not be used at any time while on study until the first progression following tisagenlecleucel infusion, Presence of active hepatitis B or hepatitis C, HIV positive patients, Clinically significant active infection confirmed by clinical evidence, imaging, or positive laboratory tests (e.g., blood cultures, PCR for DNA/RNA, etc.), Patients who, in the investigator’s judgment and/or according to clinical standards, have a contradiction to any study procedure or have any other medical condition that may put the patient at unacceptable risk., Any of the following cardiovascular conditions: a.Unstable angina, myocardial infarction, coronary artery bypass graft (CABG), or stroke within 6 months prior to screening, b.Left ventricle ejection fraction (LVEF) <45% as determined by echocardiogram (ECHO) or magnetic resonance angiography (MRA) or multigated acquisition (MUGA) at the screening assessment. c.New York Heart Association (NYHA) functional class III or IV (Chavey et al 2001), at screening or within the past 12 months. d.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. e.Resting QTcF =450 msec (male) or =460 msec (female) at screening or inability to determine the QTcF interval f.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: i.Long QT syndrome, family history of idiopathic sudden death or congenital long QT syndrome ii.Concomitant medication(s) with a Known Risk of Torsades de Pointes” per crediblemeds.org that cannot be discontinued or replaced by safe alternative medication, Previous or concurrent malignancy except for curatively treated non-melanoma skin cancers, in situ carcinoma (e.g. cervix, breast, bladder, prostate), and cancers in complete remission for at least 3 years and without evidence of recurrence, Hypersensitivity to the excipients of tisagenlecleucel or to any other drug product as advised for administration in the study protocol (e.g. lymphodepleting agents, tocilizumab), 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)), Pregnant or nursing (lactating) women Note: Women of child-bearing potential must have a negative serum pregnancy test performed within 24 hours before leukapheresis, Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless
Investigators
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