Mittwoch, 27. Januar 2021
Navigation öffnen
Anzeige:
CAR T Prelaunch
CAR T Prelaunch
 

JOURNAL ONKOLOGIE – STUDIE

BELINDA Tisagenlecleucel in Adult Patients With Aggressive B-cell Non-Hodgkin Lymphoma

Rekrutierend

NCT-Nummer:
NCT03570892

Studienbeginn:
Mai 2019

Letztes Update:
26.01.2021

Wirkstoff:
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)

Indikation (Clinical Trials):
Lymphoma, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Studienleiter

Novartis Pharmaceuticals
Study Director
Novartis Pharmaceuticals

Kontakt

Studienlocations (3 von 68)

Novartis Investigative Site
93053 Regensburg
(Bayern)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
13353 Berlin
(Berlin)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
20246 Hamburg
(Hamburg)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
50937 Koeln
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
04103 Leipzig
(Sachsen)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
81377 Muenchen
(Bayern)
GermanyRekrutierend» Google-Maps
Novartis Investigative Site
89081 Ulm
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Moores UC San Diego Cancer Center
92093 La Jolla
United StatesAktiv, nicht rekrutierend» Google-Maps
University of California Los Angeles University of California LA
90095 Los Angeles
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Gina Khachatrian
Phone: 310-825-7412
E-Mail: GKhachatrian@mednet.ucla.edu
» Ansprechpartner anzeigen
Sarah Cannon Research Institute
80218 Denver
United StatesAktiv, nicht rekrutierend» Google-Maps
Mayo Clinic Jacksonville
32224 Jacksonville
United StatesAktiv, nicht rekrutierend» Google-Maps
University of Chicago Medical Center Hematology and Oncology
60637 Chicago
United StatesAktiv, nicht rekrutierend» Google-Maps
University of Kansas Cancer Center SC
66205 Kansas City
United StatesAktiv, nicht rekrutierend» Google-Maps
Wayne State University - Karmanos Cancer Institute SC
48201 Detroit
United StatesAktiv, nicht rekrutierend» Google-Maps
University of Nebraska Medical Center
68198 Omaha
United StatesAktiv, nicht rekrutierend» Google-Maps
Duke University Medical Center
27705 Durham
United StatesZurückgezogen» Google-Maps
The Ohio State University SC
43210 Columbus
United StatesAktiv, nicht rekrutierend» Google-Maps
Oregon Health Sciences Univ SC
97239 Portland
United StatesAktiv, nicht rekrutierend» Google-Maps
University of Pennsylvania, Abramson Cancer Center
19104 Philadelphia
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Esin Namoglu
Phone: 215-662-6394
E-Mail: Esin.Namoglu@Pennmedicine.upenn.edu
» Ansprechpartner anzeigen
MUSC Hollings Cancer Center
29425 Charleston
United StatesAktiv, nicht rekrutierend» Google-Maps
Sarah Cannon Research Institute
37203 Nashville
United StatesAktiv, nicht rekrutierend» Google-Maps
University of Texas MD Anderson Cancer Center MD Anderson Cancer Center
77030 Houston
United StatesAktiv, nicht rekrutierend» Google-Maps
Methodist Hospital
78229 San Antonio
United StatesAktiv, nicht rekrutierend» Google-Maps
University of Wisconsin Carbone Cancer Center
53792-6164 Madison
United StatesAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
2010 Darlinghurst
AustraliaRekrutierend» Google-Maps
Novartis Investigative Site
3000 Melbourne
AustraliaRekrutierend» Google-Maps
Novartis Investigative Site
6150 Murdoch
AustraliaRekrutierend» Google-Maps
Novartis Investigative Site
A-6020 Innsbruck
AustriaRekrutierend» Google-Maps
Novartis Investigative Site
41253-190 Salvador
BrazilRekrutierend» Google-Maps
Novartis Investigative Site
05651-901 Sao Paulo
BrazilRekrutierend» Google-Maps
Novartis Investigative Site
59037 Lille Cedex
FranceAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
34295 Montpellier cedex 5
FranceAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
44093 Nantes Cedex 1
FranceAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
75010 Paris
FranceAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
69495 Pierre Benite Cedex
FranceAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
31059 Toulouse
FranceAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
20089 Rozzano
ItalyAktiv, nicht rekrutierend» Google-Maps
Novartis Investigative Site
00168 Roma
ItalyAktiv, nicht rekrutierend» Google-Maps
Kyushu University Hospital
812-8582 Fukuoka city
JapanRekrutierend» Google-Maps
Hokkaido University Hospital
060 8648 Sapporo city
JapanRekrutierend» Google-Maps
Tohoku University Hospital
980 8574 Sendai city
JapanRekrutierend» Google-Maps
Amsterdam UMC, locatie AMC
1105 AZ Amsterdam
NetherlandsRekrutierend» Google-Maps
UMC Utrecht Cancer Center
3584CX Utrecht
NetherlandsRekrutierend» Google-Maps
Novartis Investigative Site
119228 Singapore
SingaporeRekrutierend» Google-Maps
Novartis Investigative Site
169608 Singapore
SingaporeRekrutierend» Google-Maps
Novartis Investigative Site
08907 Hospitalet de LLobregat
SpainRekrutierend» Google-Maps
Novartis Investigative Site
8091 Zurich
SwitzerlandRekrutierend» Google-Maps
Novartis Investigative Site
B15 2TH Birmingham
United KingdomRekrutierend» Google-Maps
Novartis Investigative Site
WC1E 6HX London
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief 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.

Ein-/Ausschlusskriterien

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-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.

Studien-Rationale

Primary outcome:

1. Event-free survival (EFS) (Time Frame - 5 years):
Event-free survival (EFS) is defined as the time from the date of randomization to the date of the first documented disease progression or stable disease at or after the week 12 (+/- 1 week) assessment, as assessed by Blinded Independent Review Committee (BIRC) per Lugano criteria, or death due to any cause, at any time.



Secondary outcome:

1. EFS as assessed by local investigator (Time Frame - 5 years):
EFS as assessed by local investigator

2. Overall Survival (OS) (Time Frame - 5 years):
Overall survival (OS) is defined as the time from date of randomization to date of death due to any cause

3. Overall Response Rate (ORR) (Time Frame - 5 years):
Overall Response Rate (ORR) as per the Lugano criteria as per BIRC review and local investigator assessment

4. Duration of Response (DOR) (Time Frame - 5 years):
Duration of response: time from the date of first documented response of CR or PR to the date of first documented progression (SD or PD at or after the week 12 assessment will be considered progression) or death due to aggressive B-cell NHL. DOR will be summarized by BIRC and local response

5. Time to Response (TTR) (Time Frame - 5 years):
Time from the date of randomization to the date of a patient's first achieved a response of CR or PR on or after the Week 12 assessment

6. SF-36v2 (Time Frame - 5 years):
Time to definitive deterioration in SF-36v2

7. FACT-Lym (Time Frame - 5 years):
Time to definitive deterioration in FACT-Lym

8. EQ-VAS (Time Frame - 5 years):
Time to definitive deterioration in EQ-VAS

9. Tisagenlecleucel transgene concentrations (Time Frame - 5 years):
qPCR will be used to measure tisagenlecleucel transgene concentrations in peripheral blood and bone marrow

10. Tisagenlecleucel immunogenicity (humoral and cellular) (Time Frame - 5 years):
Pre-existing and treatment related immunogenicity (humoral and cellular) of tisagenlecleucel will be characterized.

11. Presence of replication competent lentivirus (RCL) (Time Frame - 5 years):
The presence of RCL will be assessed by VSV-qPCR in patients receiving tisagenlecleucel

Studien-Arme

  • Experimental: Tisagenlecleucel treatment strategy
    Patients will receive investigator's choice of optional platinum-based immunochemotherapy followed by lymphodepleting chemotherapy and a single dose of tisagenlecleucel
  • Active Comparator: Standard of care treatment strategy
    Patients will receive investigator's choice of platinum-based immunochemotherapy followed in responding patients by high dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT)

Geprüfte Regime

  • Tisagenlecleucel after optional bridging and lymphodepleting chemotherapy:
    Investigator's choice of optional platinum-based immunochemotherapy (ie. R-ICE, R-GemOx, R-GDP, R-DHAP) + Lymphodepleting chemotherapy (fludarabine with cyclophosphamide or bendamustine) + Tisagenlecleucel (a second generation CAR-T composed of a CD19 antigen-binding domain, a 4-1BB costimulatory domain and a CD3-ζ signaling domain)
  • Platinum-based immunochemotherapy followed in responding patients with high dose chemotherapy and autologous hematopoietic stem cell transplant (HSCT):
    Investigator's choice of platinum-based immunochemotherapy (ie. R-ICE, R-GemOx, R-GDP, R-DHAP)+ High dose chemotherapy (ie. BEAM) + autologous HSCT. *Ibrutinib or lenalidomide may be used in patients who are no longer eligible for autologous HSCT after 2 cycles of immunochemotherapy

Quelle: ClinicalTrials.gov


ASH 2020
  • Phase-III-Studie ASCEMBL bei resistenten/intoleranten Patienten mit CML: STAMP-Inhibitor Asciminib deutlich effektiver als TKI Bosutinib
  • Ruxolitinib-resistente/-intolerante MF-Patienten profitieren im klinischen Alltag möglicherweise von einer Rechallenge
  • Real-world-Daten zu PV: Rechtzeitige Umstellung von HU auf Ruxolitinib wirkt möglicherweise Anstieg thromboembolischer Ereignisse entgegen
  • 5-Jahres-Daten der RESPONSE-2-Studie: Überlegenheit von Ruxolitinib gegenüber BAT im Langzeitverlauf bestätigt
  • Phase-I-Studie: Anhaltendes molekulares Ansprechen mit neuem BCR-ABL-Inhibitor Asciminib bei CML-Patienten mit T315I-Resistenzmutation
  • Patienten mit ITP sind emotional erheblich belastet
  • r/r DLBCL: Vielversprechende erste Daten zur CAR-T-Zell-Therapie mit Tisagenlecleucel in Kombination mit Ibrutinib
  • r/r FL: CAR-T-Zell-Therapie mit Tisagenlecleucel wirksam und sicher
  • Myelofibrose: Ruxolitinib-Startdosis von 10 mg 2x tägl. auch bei initial niedriger Thrombozytenzahl sicher anwendbar
  • Phase-III-Studie REACH3: Ruxolitinib bei chronischer steroidrefraktärer oder steroidabhängiger GvHD wirksamer als die beste verfügbare Therapie