Trial Title:
Rituximab in Combination with Glofitamab and Polatuzumab Vedotin in Patients with Previously Untreated Aggressive B-cell Lymphoma Ineligible for R-CHOP
NCT ID:
NCT05798156
Condition:
Lymphoma, Large B-Cell, Diffuse
Conditions: Official terms:
Lymphoma
Lymphoma, Large B-Cell, Diffuse
Rituximab
Obinutuzumab
Polatuzumab vedotin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Glofitamab
Description:
Glofitamab is a fully humanized, engineered monoclonal bivalent antibody of the IgG1
isotype.
Arm group label:
chemolight R-Pola-Glo treatment
Intervention type:
Drug
Intervention name:
Rituximab
Description:
Rituximab is a genetically engineered chimeric mouse/human anti-CD20 monoclonal antibody
Arm group label:
chemolight R-Pola-Glo treatment
Intervention type:
Drug
Intervention name:
Obinutuzumab
Description:
Obinutuzumab is a fully humanized, glycoengineered type II monoclonal antibody of the
IgG1 isotype that binds to an epitope on CD20
Arm group label:
chemolight R-Pola-Glo treatment
Intervention type:
Drug
Intervention name:
Polatuzumab vedotin
Description:
Polatuzumab vedotin is an antibody-drug-conjugate that contains a humanized IgG1
anti-CD79b monoclonal antibody (MCDS4409A) and a potent anti-mitotic agent (MMAE) linked
through a protease-cleavable linker.
Arm group label:
chemolight R-Pola-Glo treatment
Summary:
In the present trial the chemotherapy- light treatment concept R-Pola-Glo will be
evaluated that combines the anti-CD20 antibody rituximab (R) with the ADC polatuzumab
vedotin (Pola) and the (BiMabs) glofitamab (Glo) in elderly and/or medical unfit and
previously untreated patients with aggressive B-cell lymphoma. The outcome and
feasibility data obtained here will be used for further clinical development of this new
chemolight triple combination.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Patient has provided written informed consent and is able and willing to comply with
the study protocol and protocol mandated treatments according to ICH and local
regulations.
2. Patient is above 60 years of age
3. Patient is not eligible for a fully dosed R-CHOP
4. Patient has histologically confirmed aggressive B-cell lymphoma.
5. Patient has at least one measurable FDG PET-positive lymphoma manifestation; defined
as lesional maximum FDG uptake higher than the maximum FDG uptake in unaffected
liver parenchyma as measured in a reference volume-of-interest with >10 mL
6. Baseline biopsy material is available for central review.
7. Female patients considered as women of childbearing potential (WOCBP, see section
5.2.7 for definition) and male patients with female partners considered as WOCBP
must:
1. agree to either remain completely abstinent (refrain from heterosexual
intercourse) or to use at least one effective contraceptive methods that
results in a failure rate of < 1% per year
2. refrain from donating ova (female patients) or donating sperm (male patients)
3. in case of male patients with pregnant female partners, remain abstinent
(refrain from heterosexual intercourse) or use contraceptive measures such as a
condom to avoid exposing the embryo.
8. Patient did not receive any prior systemic lymphoma therapy.
9. Patient has an ECOG performance status of ≤ 2.
10. Patient has with treatment a life expectancy (in the opinion of the investigator) of
at least 12 weeks.
11. Patient has adequate liver function
12. Patient as adequate hematological function
13. Patient has adequate renal function
14. Patients has negative serologic and/or polymerase chain reaction (PCR) test results
for:
- Acute or chronic hepatitis B (HBV) infection.
- Hepatis C virus (HCV) and human immunodeficiency virus (HIV)
15. Patient has no active SARS-CoV-2 infection.
Exclusion Criteria:
Medical conditions:
1. Patient with chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL)
(including CD20+ ALL), lymphoblastic lymphoma, Richter's transformation, Burkitt
lymphoma.
2. Patient ≤ 60 years
3. Patient with known active infection, or reactivation of a latent infection, whether
bacterial (e.g., tuberculosis), viral (including, but not limited to severe
pneumonia, COVID-19, Epstein-Barr virus [EBV], cytomegalovirus [CMV], hepatitis B,
hepatitis C, and HIV], fungal, mycobacterial, or other pathogens (excluding fungal
infections of nail beds) or any major episode of infection requiring hospitalization
or treatment with IV antibiotics (for IV antibiotics this pertains to completion of
last course of antibiotic treatment) within 4 weeks prior to study enrollment.
4. Patient with current > Grade 1 peripheral neuropathy.
5. Patient with history of confirmed progressive multifocal leukoencephalopathy (PML).
6. Patient with history of leptomeningeal disease.
7. Patient with current or history of CNS lymphoma.
8. Patient with current or history of CNS disease, such as stroke, epilepsy, CNS
vasculitis, or neurodegenerative disease with exceptions.
9. Patient with another invasive malignancy in the last 2 years (with the exception of
basal cell carcinoma and tumors deemed by the Investigator to be of low likelihood
for recurrence), with the exception of malignancies with a negligible risk of
metastasis or death (e.g., 5-year OS rate 90%), such as adequately-treated carcinoma
in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer,
ductal carcinoma in situ, or Stage I uterine cancer.
10. Patient with significant or extensive history of cardiovascular disease (such as New
York Heart Association (NYHA) Class ≥ II cardiac disease, congestive heart failure,
myocardial infarction or cerebrovascular accident within the past 3 months, unstable
arrhythmias, or unstable angina or history of multiple cardiovascular events) or
significant pulmonary disease (including obstructive pulmonary disease and history
of bronchospasm).
11. Patient with active or history of autoimmune disease or immune deficiency,
including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis,
systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease,
antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome,
Guillain-Barré syndrome, or multiple sclerosis (see addendum for a more
comprehensive list of autoimmune diseases and immune deficiencies), with exceptions.
12. Patient with uncontrolled pleural effusion, pericardial effusion, or ascites
requiring recurrent drainage procedures (once monthly or more frequently).
13. Patient with history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g.,
bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic.
Prior/Concomitant Therapy:
14. Patient received treatment with any other standard anti-cancer
radiotherapy/chemotherapy including investigational therapy (defined as treatment
for which there is currently no regulatory authority approved indication) within 4
weeks or five times the elimination half-life of the product, whichever is longer,
prior to study enrollment.
15. Patient with prior solid organ transplantation.
16. Patient with prior allogeneic stem cell transplantation.
17. Patient with prior treatment with targeted therapies (e.g., tyrosine kinase
inhibitors, systemic immunotherapeutic/immunostimulating agents, including, but not
limited to, CD137 agonists or immune checkpoint blockade therapies, including
anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies,
radio-immunoconjugates, antibody-drug conjugates, immune/cytokines, and monoclonal
antibodies) within 4 weeks or five half-lives of the drug, whichever is shorter,
prior to study enrollment.
18. Patient with toxicities from prior anti-cancer therapy including immunotherapy that
did not resolve to ≤ Grade 1 except for alopecia, endocrinopathy managed with
replacement therapy and stable vitiligo.
19. Patient with any history of immune related ≥ Grade 3 AE except for endocrinopathy
managed with replacement therapy.
20. Patient with ongoing corticosteroid use 25 mg/day of prednisone or equivalent within
4 weeks prior and during study treatment.
21. Patient with treatment with systemic immunosuppressive medication (including, but
not limited to, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti-TNF agents) within 2 weeks prior to initiation of study treatment, or
anticipation of need for systemic immunosuppressive medication during study
treatment, with exceptions.
22. Patient who received administration of a live, attenuated vaccine within 4 weeks
prior to study enrollment infusion or anticipation that such a live, attenuated
vaccine will be required during the study or within 5 months after the last dose of
study treatment.
Other Exclusions:
23. Patient with history of illicit drug or alcohol abuse within 12 months prior to
screening, in the Investigator's judgment.
24. Patient with history of severe allergic anaphylactic reactions to chimeric or
humanized monoclonal antibodies or recombinant antibody-related fusion proteins.
25. Patient with known hypersensitivity to Chinese hamster ovary (CHO) cell products or
to any component of the rituximab, obinutuzumab, polatuzumab vedotin and/or
glofitamab formulation and/or to the contrast agents used in the study.
26. Female patient is pregnant or breast feeding. Female patients of childbearing
potential must have a negative serum pregnancy test result within 7 days prior to
initiation of study treatment.
27. Patient who has been incarcerated or involuntarily institutionalized by court order
or by the authorities.
28. Patients who are unable to consent because they do not understand the nature,
significance and implications of the clinical trial and therefore cannot form a
rational intention in the light of the facts.
29. Patients who are dependent on the sponsor, the investigator or the trial site.
Gender:
All
Minimum age:
61 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Uniklinik Innsbruck
Address:
City:
Innsbruck
Country:
Austria
Status:
Recruiting
Contact:
Last name:
Ella Willenbacher, PD Dr.
Facility:
Name:
Kepler Universitätsklinikum
Address:
City:
Linz
Country:
Austria
Status:
Recruiting
Contact:
Last name:
Clemens Schmitt
Facility:
Name:
Ordensklinikum Linz - Barmherzige Schwestern
Address:
City:
Linz
Country:
Austria
Status:
Recruiting
Contact:
Last name:
Manuel Orlinger
Facility:
Name:
Ordensklinikum Linz - Elisabethinen
Address:
City:
Linz
Country:
Austria
Status:
Recruiting
Contact:
Last name:
Natalia Rotter
Facility:
Name:
Landeskrankenhaus Salzburg Universitätsklinikum der Paracelsus Medizinischen Privatuniversität
Address:
City:
Salzburg
Country:
Austria
Status:
Recruiting
Contact:
Last name:
Thomas Melchardt, Prof. Dr. med.
Facility:
Name:
Univ. Klinikum St. Pölten
Address:
City:
St. Pölten
Country:
Austria
Status:
Recruiting
Contact:
Last name:
Petra Pichler
Facility:
Name:
AKH Meduni Wien
Address:
City:
Wien
Country:
Austria
Status:
Recruiting
Contact:
Last name:
Phillip Staber
Facility:
Name:
Hanusch Krankenhaus
Address:
City:
Wien
Country:
Austria
Status:
Recruiting
Contact:
Last name:
Michael Panny
Facility:
Name:
Universitätsklinikum Magdeburg
Address:
City:
Magdeburg
Zip:
39120
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Dimitrios Mougiakakos, Prof. Dr. med.
Facility:
Name:
Charité - Universitätsmedizin Berlin
Address:
City:
Berlin
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Björn Chapuy, Prof. Dr.
Facility:
Name:
HELIOS Klinikum Berlin-Buch
Address:
City:
Berlin
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Anna Ossami Saidy, Dr.
Facility:
Name:
Medizinisches Universitätsklinikum Knappschaftskrankenhaus Bochum
Address:
City:
Bochum
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Roland Schroers, Prof. Dr.
Facility:
Name:
Klinikum Chemnitz
Address:
City:
Chemnitz
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Mathias Hänel, PD Dr. med. habil.
Facility:
Name:
Uniklinikum Düsseldorf
Address:
City:
Düsseldorf
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Sascha Dietrich
Facility:
Name:
Universitätsklinikum Erlangen
Address:
City:
Erlangen
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Fabian Müller, PD. Dr. med
Facility:
Name:
Ev. Klinikum Essen-Mitte
Address:
City:
Essen
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Peter Reimer, Prof. Dr.
Facility:
Name:
Westdeutsches Tumorzentrum Essen
Address:
City:
Essen
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Bastian von Tresckow
Facility:
Name:
Universitätsmedizin Göttingen
Address:
City:
Göttingen
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Raphael Koch
Facility:
Name:
Universitätsklinikum Halle
Address:
City:
Halle
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Thomas Weber, Dr.
Facility:
Name:
University Hospital Jena
Address:
City:
Jena
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Ulf Schnetzke, PD Dr. med.
Facility:
Name:
Universitätsklinikum Schleswig-Holstein Campus Kiel
Address:
City:
Kiel
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Christiane Pott, Prof. Dr. med.
Facility:
Name:
Universitätsklinikum Leipzig
Address:
City:
Leipzig
Zip:
04103
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Simone Heyn, Dr. med.
Facility:
Name:
Klinikum Leverkusen
Address:
City:
Leverkusen
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Utz Krug
Facility:
Name:
Klinikum Ludwigshafen
Address:
City:
Ludwigshafen
Zip:
67063
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Martin Hoffmann, Dr.
Facility:
Name:
TU München (rechts des Isar)
Address:
City:
München
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Anna Lena Illert, Prof. Dr med.
Facility:
Name:
Unversitätsklinikum Münster
Address:
City:
Münster
Zip:
48149
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Andrea Kerkhoff, MD
Facility:
Name:
Ortenauklinikum Offenburg-Kehl
Address:
City:
Offenburg
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Carsten Schwänen, PD Dr.
Facility:
Name:
Universitätsklinikum Regensburg
Address:
City:
Regensburg
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Stephanie Mayer, Dr.
Facility:
Name:
Kreiskliniken Reutlingen
Address:
City:
Reutlingen
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Angela Huster, Dr.
Facility:
Name:
Universitätsklinikum Würzburg
Address:
City:
Würzburg
Country:
Germany
Status:
Recruiting
Contact:
Last name:
Johannes Düll, Dr.
Start date:
March 20, 2023
Completion date:
September 30, 2028
Lead sponsor:
Agency:
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Agency class:
Other
Collaborator:
Agency:
Charite University, Berlin, Germany
Agency class:
Other
Collaborator:
Agency:
University of Salzburg
Agency class:
Other
Collaborator:
Agency:
Arbeitsgemeinschaft medikamentoese Tumortherapie
Agency class:
Other
Collaborator:
Agency:
Roche Pharma AG
Agency class:
Industry
Collaborator:
Agency:
Zentrum für Klinische Studien Leipzig
Agency class:
Other
Collaborator:
Agency:
Hoffmann-La Roche
Agency class:
Industry
Source:
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05798156
