Brief description of trial (Data source: BASEC)
Der Zweck dieser Studie ist der Vergleich der Wirksamkeit und Sicherheit der Behandlung mit Tisagenlecleucel gegenüber der aktuellen Standardbehandlung bei Patienten mit rezidiviertem oder refraktärem, aggressivem B-Zell-Non-Hodgkin-Lymphom. Wir wollen herausfinden, welche dieser zwei Therapien für Patienten mit dieser Erkrankung besser geeignet ist.
Health conditions investigated(Data source: BASEC)
Rezidiviertes oder refraktäres, aggressives B-Zell-Non-Hodgkin-Lymphom
Health conditions
(Data source: WHO)
Non-Hodgkin Lymphoma
Rare disease
(Data source: BASEC)
No
Intervention investigated (e.g. drug, therapy or campaign)
(Data source: BASEC)
Die Studienbehandlung Tisagenlecleucel wird auch CTL019, CART-19 oder Kymriah® genannt. Zur Herstellung von Tisagenlecleucel werden T-Zellen (eine Art von weissen Blutkörperchen) aus dem Blut des Patienten entnommen. Die T-Zellen werden von Novartis so verändert, dass sie die Tumorzellen (B-Zellen, eine andere Art von weisser Blutkörperchen) erkennen und bekämpfen können. Die Modifizierung der T-Zellen erfolgt durch einen Prozess namens Gentransfer, der zu einer genetischen Veränderung der T-Zellen führt. Die modifizierten T-Zellen werden als Tisagenlecleucel bezeichnet und werden dem Patienten über eine intravenöse Infusion verabreicht.
Die eine Hälfte der Studienteilnehmer wird mit Tisagenlecleucel behandelt, die andere Hälfte erhält eine Standard-Immunchemotherapie. Die Zuteilung erfolgt per Zufall. Während 5 Jahren finden regelmässige Kontrollvisiten am Studienzentrum statt, damit die Gesundheit der Studienteilnehmer überwacht werden kann.
Interventions
(Data source: WHO)
Drug: Tisagenlecleucel after optional bridging and lymphodepleting chemotherapy;Drug: Platinum-based immunochemotherapy followed in responding patients with high dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT)
Criteria for participation in trial
(Data source: BASEC)
- Männer und Frauen im Alter von mindestens 18 Jahren
- Histologisch (durch Begutachtung unter dem Mikroskop) bestätigtes B-Zell-Non-Hodgkin-Lymphom
- Patienten, die auf eine erste Immunchemotherapie nicht ausreichend angesprochen haben oder innerhalb von 365 Tagen eine Progression oder einen Rückfall erlitten.
Exclusion criteria
(Data source: BASEC)
- Patienten welche mehr als eine vorherige Krebstherapie zur Bekämpfung der Lymphomerkrankung erhalten haben.
- Patienten bei welchen eine allogene Stammzelltransplantation durchgeführt wurde.
- Schwangere und stillende Frauen können nicht an dieser Studie teilnehmen.
Inclusion/Exclusion Criteria
(Data source: WHO)
Gender: All
Maximum age: N/A
Minimum age: 18 Years
Inclusion Criteria:
1. 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):
1. DLBCL, NOS,
2. FL grade 3B,
3. Primary mediastinal large B cell lymphoma (PMBCL),
4. T cell rich/histiocyte rich large B cell lymphoma (T/HRBCL),
5. DLBCL associated with chronic inflammation,
6. Intravascular large B-cell lymphoma,
7. ALK+ large B-cell lymphoma,
8. B-cell lymphoma, unclassifiable, (with features intermediate between DLBCL and
classical Hodgkin's Lymphoma (HL)),
9. High grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements,
10. High-grade B-cell lymphoma, NOS
11. HHV8+ DLBCL, NOS
12. DLBCL transforming from follicular lymphoma
13. DLBCL transforming from marginal zone lymphoma
14. DLBCL, leg type
2. 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).
3. 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
4. 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::
1. Nodal lesions >15 mm in the long axis, regardless of the length of the short
axis, and/or
2. Extranodal lesions (outside lymph node or nodal mass, but including liver and
spleen) >10 mm in long AND short axis
5. Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
6. Adequate organ function:
Renal function defined as:
1. 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:
2. Alanine Transaminase (ALT) and Aspartate Transiminase (AST) = 5 ? ULN
3. 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:
4. Absolute neutrophil count (ANC) >1000/mm3
5. Absolute lymphocyte count (ALC) >300/mm3 OR Absolute number of CD3+ T cells
>150/mm3 (only for patients with non-historical apheresis)
6. Platelets =50000/mm3
7. Hemoglobin >8.0 g/dl
Adequate pulmonary function defined as:
8. No or mild dyspnea (= Grade 1)
9. Oxygen saturation measured by pulse oximetry > 90% on room air
10. Forced expiratory volume in 1 s (FEV1) = 50% and/or carbon monoxide diffusion
test (DLCO) =50% of predicted level
7. Must have a leukapheresis material of non-mobilized cells available for manufacturing.
Exclusion Criteria:
1. Prior treatment with anti-CD19 therapy, T cell therapy, or any prior gene therapy
product
2. Treatment with any systemic lymphoma-directed second line anticancer therapy prior to
randomization. Only steroids and local irradiation are permitted for disease control
3. 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
4. Prior allogeneic HSCT
5. Clinically significant active infection
6. 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.
7. Patients with active neurological autoimmune or inflammatory disorders (e.g.,
Guillain-Barr? 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.
-
Further information on trial
Recruitment status
Active, not recruiting
Academic title
(Data source: WHO)
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)
Type of trial
(Data source: WHO)
Interventional
Design of the trial
(Data source: WHO)
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Single (Outcomes Assessor).
Phase
(Data source: WHO)
Phase 3
Primary end point
(Data source: WHO)
Event-free survival (EFS)
Secundary end point
(Data source: WHO)
EFS as assessed by local investigator;Overall Survival (OS);Overall Response Rate (ORR);Duration of Response (DOR);Time to Response (TTR);SF-36v2;FACT-Lym;EQ-VAS;Tisagenlecleucel transgene concentrations;Tisagenlecleucel immunogenicity (humoral and cellular);Presence of replication competent lentivirus (RCL)
Contact information
(Data source: WHO)
Please refer to primary and secondary sponsors
Trial results
(Data source: WHO)
Results summary
no information available yet
Link to the results in the primary register
no information available yet
Information on the availability of individual participant data
no information available yet
Trial sites
Trial sites in Switzerland
(Data source: BASEC)
Zurich
Countries
(Data source: WHO)
Australia, Austria, Belgium, Brazil, China, France, Germany, Hong Kong, Italy, Japan, Netherlands, Norway, Singapore, Spain, Switzerland, Taiwan, United Kingdom, United States
Contact for further information on the trial
Details of contact in Switzerland
(Data source: BASEC)
Vera Luginbühl
+41793368901
vera.luginbuehl@novartis.com
Contact for general information
(Data source: WHO)
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Contact for scientific information
(Data source: WHO)
Novartis Pharmaceuticals
Novartis Pharmaceuticals
Authorisation by the ethics committee (Data source: BASEC)
Name of the authorising ethics committee (for multicentre studies only the lead committee)
Kantonale
Ethikkommission Zürich
Date of authorisation by the ethics committee
07.05.2019
Further trial identification numbers
Trial identification number of the ethics committee (BASEC-ID)
(Data source: BASEC)
2018-01892
Secondary ID (Data source: WHO)
2016-002966-29
CCTL019H2301
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