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History of Changes for Study: NCT05798156
Rituximab in Combination With Glofitamab and Polatuzumab Vedotin in Patients With Previously Untreated Aggressive Large B-cell Lymphoma Ineligible for R-CHOP (R-Pola-Glo)
Latest version (submitted December 15, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 March 22, 2023 None (earliest Version on record)
2 May 30, 2023 Recruitment Status, Study Status, Contacts/Locations, Eligibility, Study Description, Oversight and Study Identification
3 December 15, 2023 Contacts/Locations, Study Status and Study Identification
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Study NCT05798156
Submitted Date:  March 22, 2023 (v1)

Open or close this module Study Identification
Unique Protocol ID: R-Pola-Glo
Brief Title: Rituximab in Combination With Glofitamab and Polatuzumab Vedotin in Patients With Previously Untreated Aggressive Large B-cell Lymphoma Ineligible for R-CHOP (R-Pola-Glo)
Official Title: A Prospective Multicenter Phase 2 Study of the Chemotherapy-light Combination of Intravenous Rituximab With the Antibody-drug Conjugate Polatuzumab Vedotin and the Bispecific Antibody Glofitamab in Previously Untreated Aggressive Large Bcell Lymphoma Patients Above 60 Years of Age Ineligible for a Fully Dosed R-CHOP
Secondary IDs: 2022-003398-51 [EudraCT Number]
GLA 2022-10 [GLA]
NHL-16 [AGMT]
ML44400 [Other Grant/Funding Number: Roche]
Open or close this module Study Status
Record Verification: February 2023
Overall Status: Not yet recruiting
Study Start: March 31, 2023
Primary Completion: September 30, 2027 [Anticipated]
Study Completion: September 30, 2028 [Anticipated]
First Submitted: March 8, 2023
First Submitted that
Met QC Criteria:
March 22, 2023
First Posted: April 4, 2023 [Actual]
Last Update Submitted that
Met QC Criteria:
March 22, 2023
Last Update Posted: April 4, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest
Responsible Party: Sponsor
Collaborators: Charite University, Berlin, Germany
University of Salzburg
Arbeitsgemeinschaft medikamentoese Tumortherapie
Roche Pharma AG
Zentrum für Klinische Studien Leipzig
Hoffmann-La Roche
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module Study Description
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 efficacy and feasibility data obtained here will be used for further clinical development of this new chemolight triple combination.
Detailed Description:
Open or close this module Conditions
Conditions: Lymphoma, Large B-Cell, Diffuse
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 2
Interventional Study Model: Single Group Assignment
Number of Arms: 1
Masking: None (Open Label)
Allocation: N/A
Enrollment: 80 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: chemolight R-Pola-Glo treatment Drug: Glofitamab
Glofitamab is a fully humanized, engineered monoclonal bivalent antibody of the IgG1 isotype.
Drug: Rituximab
Rituximab is a genetically engineered chimeric mouse/human anti-CD20 monoclonal antibody
Drug: Obinutuzumab
Obinutuzumab is a fully humanized, glycoengineered type II monoclonal antibody of the IgG1 isotype that binds to an epitope on CD20
Drug: Polatuzumab vedotin
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.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 1 year progression-free survival (PFS) rate
[ Time Frame: 12 months ]

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
Secondary Outcome Measures:
1. Event-free survival (EFS)
[ Time Frame: 54 months ]

defined as the time from the day of inclusion until progressive disease or relapse after complete remission, initiation of subsequent systemic antilymphoma treatment, radiation of single PET-CT positive lesions or death due to any cause, whichever occurs first.
2. Overall survival (OS)
[ Time Frame: 54 months ]

defined as the time from the day of inclusion until death due to any cause
3. Response rate at different timepoints
[ Time Frame: 6 weeks, 18 weeks, 36 weeks ]

Response rates after 2 cycles (during target dose phase), 6 cycles (end of target dose phase before start of consolidation phase) and 12 cycles (end of treatment following completion of consolidation phase). i.e., complete remission (CR) rate, partial remission (PR) rate, overall remission rate (ORR: CR+PR), stable disease (SD) rate and progressive disease (PD) rate
4. Relapse rate
[ Time Frame: 54 months ]

defined as the number of patients with relapse, divided by the number of patients achieving C
5. Conversion rate of PR to CR
[ Time Frame: 54 months ]

defined as the number of patients achieving mCR at the end of study treatment (including consolidation phase) divided by the number of patients achieving PR after end of target dose phase (before start of consolidation phase)
6. Duration of response (DoR)
[ Time Frame: 54 months ]

defined as the time from documentation of CR until relapse or lymphoma associated death without documented relapse
7. Rate and type of adverse events (AEs) and serious adverse events (SAEs)
[ Time Frame: 54 months ]

8. Rate of secondary malignancies
[ Time Frame: 54 months ]

defined as the number of patients with secondary malignancies divided by the number of analyzable patients
9. Treatment-related death rate
[ Time Frame: 54 months ]

defined as the number of treatment related deaths during therapy or up to 2 months after the end of study treatment, but before the start of further treatment, divided by the number of analyzable patients
10. Protocol adherence
[ Time Frame: 54 months ]

number and duration of R-Pola-Glo cycles, number and duration of glofitamab maintenance, cumulative and relative doses of rituximab, glofitamab and polatuzumab.
11. Patient-reported outcomes for quality of life (QoL): EORTC QLQ-C30
[ Time Frame: 54 months ]

measured by EORTC QLQ-C30 (a 30-item questionnaire developed by the European Organisation for Research and Treatment of Cancer). All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.
12. Patient-reported outcomes for quality of life (QoL): FACT-Lym
[ Time Frame: 54 months ]

measured by FACT-Lym (Functional Assessment of Cancer Therapy - Lymphoma; scores from 0 - 4; The higher the score, the better the QOL)
Other Outcome Measures:
1. Rate of minimal residual disease (MRD)-negative patients after end of target phase and at end of treatment
[ Time Frame: 54 months ]

2. Duration of molecular remission for MRD negative patients
[ Time Frame: 54 months ]

Open or close this module Eligibility
Minimum Age: 61 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  1. Patient is able and willing to provide written informed consent and to comply with the study protocol and protocol mandated hospitalizations 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 (,ale 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 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 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.
Open or close this module Contacts/Locations
Central Contact Person: Björn Chapuy, Univ.-Prof. Dr. med.
Telephone: +49 30 450 613423
Email: bjoern.chapuy@charite.de
Central Contact Backup: Richard Greil, Univ. Prof. Dr. med.
Email: r.greil@salk.at
Study Officials: Salah-Eddin Al-Batran, Prof. Dr.
Study Chair
Institut fuer Klinische Krebsforschung IKF GmbH
Locations: Austria
Kepler Universitätsklinikum
Linz, Austria
Contact:Contact: Clemens Schmitt
Ordensklinikum Linz - Barmherzige Schwestern
Linz, Austria
Ordensklinikum Linz - Elisabethinen
Linz, Austria
Contact:Contact: Natalia Rotter
Landeskrankenhaus Salzburg Universitätsklinikum der Paracelsus Medizinischen Privatuniversität
Salzburg, Austria
Contact:Contact: Richard Greil, Prof. Dr. med.
Univ. Klinikum St. Pölten
St. Pölten, Austria
Contact:Contact: Petra Pichler
AKH Meduni Wien
Wien, Austria
Contact:Contact: Phillip Staber
Hanusch Krankenhaus
Wien, Austria
Germany
Charité - Universitätsmedizin Berlin
Berlin, Germany
Contact:Contact: Björn Chapuy, Prof. Dr.
HELIOS Klinikum Berlin-Buch
Berlin, Germany
Contact:Contact: Pearl van Heteren, Dr.
Klinikum Chemnitz
Chemnitz, Germany
Contact:Contact: Mathias Hänel, PD Dr. med. habil.
Universitätsklinikum Erlangen
Erlangen, Germany
Contact:Contact: Fabian Müller, PD. Dr. med
University Hospital Jena
Jena, Germany
Contact:Contact: Ulf Schnetzke, PD Dr. med.
Universitätsklinikum Schleswig-Holstein Campus Kiel
Kiel, Germany
Universitätsklinikum Leipzig
Leipzig, Germany, 04103
Contact:Contact: Simone Heyn, Dr. med.
Klinikum Ludwigshafen
Ludwigshafen, Germany, 67063
Contact:Contact: Martin Hoffmann, Dr.
TU München (rechts des Isar)
München, Germany
Contact:Contact: Anna Lena Illert, Prof. Dr med.
Unversitätsklinikum Münster
Münster, Germany, 48149
Universitätsklinikum Würzburg
Würzburg, Germany
Contact:Contact: Johannes Düll, Dr.
Open or close this module IPDSharing
Plan to Share IPD: No
No IPD will be shared.
Open or close this module References
Citations:
Links:
Available IPD/Information:

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