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Tisagenlecleucel in adult patients with aggressive B-cell non-Hodgkin lymphoma
EU CTIS ID: 2023-508343-48-00
What this study is testing
Compare tisagenlecleucel treatment strategy to SOC treatment strategy with respect to delaying the composite event of disease progression (PD)/stable disease (SD) at or after the Week 12 assessment; or death at any time.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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
You likely can't join if
- 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
See the full eligibility criteria
Who can join
- 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
What rules you out
- 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 they are using highly effective methods of contraception starting from the time of informed consent form (ICF) signature and for: - at least 12 months after the tisagenlecleucel infusion and until CART cells are no longer present by qPCR on two consecutive tests for patients in Arm A or patients who crossover. - a duration according to local label and physician recommendations for patients randomized to Arm B (SOC). Furthermore, patients may need to also add barrier contraception methods if required by the local label. Highly effective contraception methods include: - Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception - Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy), total hysterectomy, or bilateral tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment - Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant - Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception. - In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking study treatment. - Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child bearing potential. Note: If local regulations deviate from the contraception methods listed above to prevent pregnancy, local regulations apply and will be described in the ICF. In addition, participants must not donate oocytes.
- Sexually active males who do not use a condom during intercourse starting from the time of ICF signature and for: - at least 12 months after the tisagenlecleucel infusion and until CAR T-cells are no longer present by qPCR on two consecutive tests for patients in Arm A or patients who crossover. - a duration according to local label and physician recommendations for patients randomized to Arm B (SOC) A condom is required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, participants must not donate sperm.
- Prior treatment with anti-CD19 therapy, adoptive T cell therapy, or any prior gene therapy product
The study team makes the final eligibility decision.
Where it's taking place
- China
- Brazil
- Singapore
- Australia
- United Kingdom
- United States
- Taiwan
- Hong Kong
- Canada
- Switzerland
- Japan
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include China; Brazil; Singapore; Australia; United Kingdom; United States and 5 more location(s). Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.