Study With Mosunetuzumab and Zanubrutinib in R/R Follicular Lymphoma Patients
FIL_MOZART
A Phase II Trial Investigating MOsunetuzumab and ZAnubrutinib (BGB-3111) in Relapsed/refracTory Follicular Lymphoma Patients (MOZART)
1 other identifier
interventional
56
2 countries
24
Brief Summary
This is a Phase 2, multicenter study evaluating the efficacy and safety of mosunetuzumab + zanubrutinib (M+Z) used as salvage strategy in patients with R/R FL who have received at least one line of prior systemic therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Oct 2024
Longer than P75 for phase_2
24 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 1, 2024
CompletedFirst Posted
Study publicly available on registry
July 9, 2024
CompletedStudy Start
First participant enrolled
October 23, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 15, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
September 15, 2033
January 28, 2026
January 1, 2026
3.9 years
July 1, 2024
January 26, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Complete Response Rate (CRR)
CRR at the end of the induction therapy
36 months
Secondary Outcomes (10)
Overall Response Rate (ORR), Partial Response (PR) Rate at the end of induction treatment (EOI)
36 months
Overall Response Rate (ORR), Partial Response (PR) Rate at the end of maintenance (EOT, end of treatment)
48 months
Progression Free Survival (PFS)
108 months
Overall Survival (OS)
108 months
Duration of Response (DOR)
108 months
- +5 more secondary outcomes
Study Arms (1)
Mosunetuzumab in combination with Zanubrutinib
EXPERIMENTALPre-phase: Zanubrutinib 320 mg daily by mouth (D-15 to D-1) Induction phase cycle 1 (Q21 days): * Zanubrutinib 320 mg daily by mouth (D1-21) * Mosunetuzumab 5 mg, SC (D1) * Mosunetuzumab 45 mg, SC (D8) * Mosunetuzumab 45 mg, SC (D15) Induction phase cycles 2-12 (Q28 days): * Zanubrutinib 320 mg daily by mouth (D1-28) * Mosunetuzumab 45 mg, SC (D1) Maintenance phase cycles 13-24 (Q28 days): Zanubrutinib 320 mg daily by mouth (D1-28) Tocilizumab will be administered as needed to manage cytokine release syndrome (CRS) events.
Interventions
Combinations of Mosunetuzumab and Zanubrutinib as salvage strategy in patients with relapsed/refractory follicular lymphoma who have received at least one line of prior systemic therapy.
Eligibility Criteria
You may qualify if:
- Able to provide written informed consent form approved by the National Ethics Committee (NEC) prior to the initiation of any screening or study-specific procedures and able to understand and to comply with the requirements of the study and the schedule of assessments.
- Histologically documented diagnosis of cFL (CD20+ by flow cytometry or immunohistochemistry) as defined in the International Consensus Classification of Mature Lymphoid Neoplasms (Campo E., 2022) and in the World Health Organization Classification (WHO) 5th edition 2022.
- Age ≥18 years.
- Relapsed or refractory disease. Histologic confirmation of FL relapse is not mandatory but is highly recommended.
- At least one and up to three lines of systemic therapy containing an anti-CD20 antibody (anti-CD20 alone and/or in combination with radiotherapy is not considered as a line of therapy).
- FL requiring systemic therapy assessed by investigator based on tumor size and/or Groupe d'Etude des Lymphomes Folliculaires criteria.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
- Availability of histological material for centralized revision. Central pathology review is not mandatory for start of treatment.
- At least one measurable or evaluable site of disease at relapse as documented by CT scan (nodes ≥ 1.5 cm in the longest transverse diameter) or FDG-PET (avid FDG sites). Note: MRI is allowed only if CT scan cannot be performed. Patients with exclusive bone marrow involvement are eligible.
- Adequate hematological counts defined as follows:
- Absolute neutrophil count (ANC) \> 1.0 x 109/L;
- Platelet count ≥ 75 x 109/L;
- Hemoglobin ≥ 9 g/dL.
- Adequate renal function defined as creatinine clearance ≥ 40 mL/min (Cockcroft-Gault formula, normalized to 1.72 m2).
- Adequate hepatic function per local laboratory reference range as follows:
- +13 more criteria
You may not qualify if:
- Histological diagnosis different from cFL (Campo E., 2022).
- R/R FL who were treated with more than three lines of previous treatment (autologous stem cell transplant performed as part of consolidation to a previous line of therapy should not be considered as a line of therapy; rituximab maintenance as part of a previous line of therapy should not be considered as a line of therapy; radiotherapy alone or in combination with rituximab is not considered a line of therapy).
- Patients with stage I or II (limited stage) suitable for RT alone treatment.
- Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor (BTKi).
- Prior exposure to an anti-CD20xCD3 bispecific antibody (bsAbs).
- Need of anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon). Requires ongoing treatment with a strong CYP3A inducer.
- Evidence or any history of transformation from FL to other aggressive histology.
- Prior allogeneic hematopoietic stem cell transplantation.
- History of severe bleeding disorder (G\>3), or history of spontaneous bleeding requiring blood transfusion or other medical intervention. History of stroke or intracranial hemorrhage within 6 months before first dose of study drug
- Life expectancy \< 6 months.
- History of progressive multifocal leukoencephalopathy (PML).
- History of hemophagocytic lymphohistiocytosis (HLH) or chronic active EBV.
- History of autoimmune disease, including, but not limited to: myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
- Primary central nervous system (CNS) lymphoma or CNS involvement by lymphoma at screening as confirmed by mandatory brain computed tomography (CT) scan and, if clinically indicated, by lumbar puncture.
- Subject has received any anti-cancer therapy including chemotherapy, immunotherapy, radiotherapy, investigational therapy, including targeted small molecule agents within 14 days prior to the first dose of study drug. If receiving glucocorticoid treatment at screening, must be a maximum daily dose of prednisone 10 mg (or equivalent).
- +21 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (24)
Royal Adelaide Hospital
Adelaide, Australia
Liverpool Hospital
Liverpool, Australia
St. Vincent Hospital Melbourne
Melbourne, Australia
Princess Alexandra Hospital
Woolloongabba, Australia
Fondazione del Piemonte per l'Oncologia - IRCCS, Ematologia
Candiolo, Torino, Italy
AOU SS. Antonio e Biagio e Cesare Arrigo, SCDU Ematologia
Alessandria, Italy
AOU Ospedali Riuniti, Clinica di Ematologia
Ancona, Italy
Azienda Ospedaliera S.Giuseppe Moscati, S.C. Ematologia e Trapianto emopoietico
Avellino, Italy
IRCCS Istituto Tumori Giovanni Paolo II, U.O.C Ematologia
Bari, Italy
Policlinico S.Orsola-Malpighi, Istituto di Ematologia "Seragnoli"
Bologna, Italy
ASST Spedali Civili di Brescia, Ematologia
Brescia, Italy
Azienda Ospedaliera Universitaria Policlinico - S. Marco, UOC di Ematologia
Catania, Italy
Azienda Ospedaliera Universitaria Careggi, Unità funzionale di Ematologia
Florence, Italy
ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia
Milan, Italy
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Ematologia
Milan, Italy
Fondazione IRCCS San Gerardo dei Tintori, Ematologia
Monza, Italy
AOU Maggiore della Carità di Novara, SCDU Ematologia
Novara, Italy
A.O. Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia
Palermo, Italy
Azienda USL Piacenza, UOC Ematologia e Centro Trapianti
Piacenza, Italy
Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova, Ematologia
Reggio Emilia, Italy
Ospedale degli Infermi di Rimini, U.O. di Ematologia
Rimini, Italy
Policlinico Umberto I - Università La Sapienza, Istituto Ematologia, Dipartimento di Medicina Traslazionale e di Precisione
Roma, Italy
A.O.U. Città della Salute e della Scienza di Torino, S.C.Ematologia
Torino, Italy
Ospedale Ca' Foncello, S.C di Ematologia
Treviso, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Marco Ladetto, Prof
Department of Translational Medicine of the Università degli Studi del Piemonte Orientale, Novara, Italy. AO SS Antonio e Biagio e C. Arrigo, Alessandria, Italy.
- PRINCIPAL INVESTIGATOR
Stefano Luminari, Prof
Oncology and Regenerative Medicine, University of Modena and Reggio Emilia, Modena, Italy. Hematology Unit of AUSL-IRCCS Arcispedale Santa Maria Nuova, Reggio Emilia, Reggio Emilia, Italy.
Central Study Contacts
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
July 1, 2024
First Posted
July 9, 2024
Study Start
October 23, 2024
Primary Completion (Estimated)
September 15, 2028
Study Completion (Estimated)
September 15, 2033
Last Updated
January 28, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ANALYTIC CODE
- Time Frame
- In compliance with the domestic ethics guideline and applicable legislation, invidual deindentified patients' data underlying the results reported in the publication article (including study protocol, statistical analysis plan and data coding) can be shared until 5 years after the publication of the article.
- Access Criteria
- For each data sharing request, it is essential that a proforma (available on request) is completed that describes the general purpose, specific aims, data items requested, analysis plan and acknowledgment of the trial management team. Requests will be reviewed based on scientific merit and ethical principles. Requestors who are granted access to the data will be required to complete a data sharing agreement that will be signed by the requester and FIL.
Qualified researchers may contact the FIL board at segreteriadirezione@filinf.it to share invidual-level patients' clinical data analysed for this manuscript (for the avoidance of doubt, no identifiable data, such as name, address, hospital name, date of birth, or any other identifying data, will be shared and should not be requested).