Rituximab in Combination With Glofitamab and Polatuzumab Vedotin in Patients With Previously Untreated Aggressive B-cell Lymphoma Ineligible for R-CHOP

NCT05798156 | Active Not Recruiting Phase 2

• 6 other identifiers: R-Pola-GloML444002022-003398-51GLA 2022-10NHL-16IKF-t062
• Study Type: interventional
• Target: 125
• Locations: 2 countries
• Sites: 28

Brief 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.

Conditions

Lymphoma, Large B-Cell, Diffuse

Outcome Measures

Primary Outcomes (1)

• 1 year progression-free survival (PFS) rate of the first 80 patients

  defined as the time from the day of inclusion until disease progression (PD) or relapse after complete remission (CR), or death due to any cause, whichever occurs first

  12 months

Secondary Outcomes (12)

• Event-free survival (EFS)

  54 months

• Overall survival (OS)

  54 months

• Response rate at different timepoints

  6 weeks, 18 weeks, 36 weeks

• Relapse rate

  54 months

• Conversion rate of PR to CR

  54 months

Other Outcomes (5)

• Rate of minimal residual disease (MRD)-negative patients after end of target phase and at end of treatment

  54 months

• Duration of molecular remission for MRD negative patients

  54 months

• Outpatient setting w/o hospitalization

  During Cycle 1-6

Study Arms (1)

chemolight R-Pola-Glo treatment

EXPERIMENTAL

Drug: Glofitamab; Drug: Rituximab; Drug: Obinutuzumab; Drug: Polatuzumab vedotin

Interventions

Glofitamab DRUG

Glofitamab is a fully humanized, engineered monoclonal bivalent antibody of the IgG1 isotype.

chemolight R-Pola-Glo treatment

Rituximab DRUG

Rituximab is a genetically engineered chimeric mouse/human anti-CD20 monoclonal antibody

chemolight R-Pola-Glo treatment

Obinutuzumab DRUG

Obinutuzumab is a fully humanized, glycoengineered type II monoclonal antibody of the IgG1 isotype that binds to an epitope on CD20

chemolight R-Pola-Glo treatment

Polatuzumab vedotin DRUG

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.

chemolight R-Pola-Glo treatment

Eligibility Criteria

• Age: 61 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Patient is above 60 years of age
• Patient is not eligible for a fully dosed R-CHOP
• Patient has histologically confirmed aggressive B-cell lymphoma.
• 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
• Baseline biopsy material is available for central review.
• 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:
• 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
• refrain from donating ova (female patients) or donating sperm (male patients)
• 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.
• Patient did not receive any prior systemic lymphoma therapy.
• Patient has an ECOG performance status of ≤ 2.
• Patient has with treatment a life expectancy (in the opinion of the investigator) of at least 12 weeks.
• Patient has adequate liver function
• Patient as adequate hematological function

You may not qualify if:

• Medical conditions:
• Patient with chronic lymphocytic leukemia (CLL), acute lymphoblastic leukemia (ALL) (including CD20+ ALL), lymphoblastic lymphoma, Richter's transformation, Burkitt lymphoma.
• Patient ≤ 60 years
• 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.
• Patient with current \> Grade 1 peripheral neuropathy.
• Patient with history of confirmed progressive multifocal leukoencephalopathy (PML).
• Patient with history of leptomeningeal disease.
• Patient with current or history of CNS lymphoma.
• Patient with current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease with exceptions.
• 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.
• 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).
• 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.
• Patient with uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently).
• Patient with history of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic.
• Prior/Concomitant Therapy:

Sponsors & Collaborators

• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead
• Charite University, Berlin, Germany: collaborator
• University of Salzburg: collaborator
• Arbeitsgemeinschaft medikamentoese Tumortherapie: collaborator
• Roche Pharma AG: collaborator
• Zentrum für Klinische Studien Leipzig: collaborator
• Hoffmann-La Roche: collaborator

Study Sites (28)

Uniklinik Innsbruck

Innsbruck, Austria

Location

Kepler Universitätsklinikum

Linz, Austria

Location

Ordensklinikum Linz - Barmherzige Schwestern

Linz, Austria

Location

Ordensklinikum Linz - Elisabethinen

Linz, Austria

Location

Landeskrankenhaus Salzburg Universitätsklinikum der Paracelsus Medizinischen Privatuniversität

Salzburg, Austria

Location

Univ. Klinikum St. Pölten

Sankt Pölten, Austria

Location

AKH Meduni Wien

Vienna, Austria

Location

Hanusch Krankenhaus

Vienna, Austria

Location

Universitätsklinikum Magdeburg

Magdeburg, Saxony-Anhalt, 39120, Germany

Location

Charité - Universitätsmedizin Berlin

Berlin, Germany

Location

HELIOS Klinikum Berlin-Buch

Berlin, Germany

Location

Medizinisches Universitätsklinikum Knappschaftskrankenhaus Bochum

Bochum, Germany

Location

Klinikum Chemnitz

Chemnitz, Germany

Location

Uniklinikum Düsseldorf

Düsseldorf, Germany

Location

Universitätsklinikum Erlangen

Erlangen, Germany

Location

Ev. Klinikum Essen-Mitte

Essen, Germany

Location

Westdeutsches Tumorzentrum Essen

Essen, Germany

Location

Universitätsklinikum Halle

Halle, Germany

Location

University Hospital Jena

Jena, Germany

Location

Universitätsklinikum Schleswig-Holstein Campus Kiel

Kiel, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Klinikum Ludwigshafen

Ludwigshafen, 67063, Germany

Location

TU München (rechts des Isar)

München, Germany

Location

Unversitätsklinikum Münster

Münster, 48149, Germany

Location

Ortenauklinikum Offenburg-Kehl

Offenburg, Germany

Location

Universitätsklinikum Regensburg

Regensburg, Germany

Location

Kreiskliniken Reutlingen

Reutlingen, Germany

Location

Universitätsklinikum Würzburg

Würzburg, Germany

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Interventions

glofitamab; Rituximab; obinutuzumab; polatuzumab vedotin

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Salah-Eddin Al-Batran, Prof. Dr.

  Institut fuer Klinische Krebsforschung IKF GmbH

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 8, 2023
• First Posted: April 4, 2023
• Study Start: March 20, 2023
• Primary Completion: April 12, 2025
• Study Completion (Estimated): February 28, 2028
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AU (8); DE (20)