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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06492837




Registration number
NCT06492837
Ethics application status
Date submitted
1/07/2024
Date registered
9/07/2024
Date last updated
13/08/2025

Titles & IDs
Public title
Study With Mosunetuzumab and Zanubrutinib in R/R Follicular Lymphoma Patients
Scientific title
A Phase II Trial Investigating MOsunetuzumab and ZAnubrutinib (BGB-3111) in Relapsed/refracTory Follicular Lymphoma Patients (MOZART)
Secondary ID [1] 0 0
FIL_MOZART
Universal Trial Number (UTN)
Trial acronym
FIL_MOZART
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Follicular Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mosunetuzumab in combination with Zanubrutinib

Experimental: Mosunetuzumab in combination with Zanubrutinib - Pre-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.


Treatment: Drugs: Mosunetuzumab in combination with Zanubrutinib
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.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Complete Response Rate (CRR)
Timepoint [1] 0 0
36 months
Secondary outcome [1] 0 0
Overall Response Rate (ORR), Partial Response (PR) Rate at the end of induction treatment (EOI)
Timepoint [1] 0 0
36 months
Secondary outcome [2] 0 0
Overall Response Rate (ORR), Partial Response (PR) Rate at the end of maintenance (EOT, end of treatment)
Timepoint [2] 0 0
48 months
Secondary outcome [3] 0 0
Progression Free Survival (PFS)
Timepoint [3] 0 0
108 months
Secondary outcome [4] 0 0
Overall Survival (OS)
Timepoint [4] 0 0
108 months
Secondary outcome [5] 0 0
Duration of Response (DOR)
Timepoint [5] 0 0
108 months
Secondary outcome [6] 0 0
Duration of Complete Response (DOCR)
Timepoint [6] 0 0
108 months
Secondary outcome [7] 0 0
Time-to-next-treatment (TTNT)
Timepoint [7] 0 0
108 months
Secondary outcome [8] 0 0
Event free survival (EFS)
Timepoint [8] 0 0
108 months
Secondary outcome [9] 0 0
Frequency and severity of Adverse Events (AEs) and Serious AEs (SAEs)
Timepoint [9] 0 0
108 months
Secondary outcome [10] 0 0
Frequency and severity of cytokine release syndrome (CRS) and Neurological Adverse Events (NAE)
Timepoint [10] 0 0
36 months

Eligibility
Key inclusion criteria
1. 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.
2. 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.
3. Age =18 years.
4. Relapsed or refractory disease. Histologic confirmation of FL relapse is not mandatory but is highly recommended.
5. 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).
6. FL requiring systemic therapy assessed by investigator based on tumor size and/or Groupe d'Etude des Lymphomes Folliculaires criteria.
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) = 2.
8. Availability of histological material for centralized revision. Central pathology review is not mandatory for start of treatment.
9. 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.
10. 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.
11. Adequate renal function defined as creatinine clearance = 40 mL/min (Cockcroft-Gault formula, normalized to 1.72 m2).
12. Adequate hepatic function per local laboratory reference range as follows:

* Aspartate transaminase (AST) and alanine transaminase (ALT) = 2.5 x ULN;
* Bilirubin =1.5 x ULN (unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin).
13. Subject must be able to adhere to the study visit schedule and other protocol requirements.
14. Subject must be able to swallow capsules or tablets.
15. Women must be:

* postmenopausal for at least 1 year (must not have had a natural menses for at least 12 months);
* surgically sterile (have had a hysterectomy or bilateral oophorectomy, tubal ligation, or otherwise be incapable of pregnancy);
* if they are childbearing potential, completely abstinent (periodic abstinence is not permitted) or if sexually active, be practicing a highly effective method of birth control (e.g., prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device, double barrier method (e.g.: condoms, diaphragm, or cervical cap, with spermicidal foam, cream, or gel, male partner sterilization), before entry, and must agree to continue to use the same method of contraception throughout the study and for 30 days after receiving the last dose of zanubrutinib and 3 months after receiving the last dose of mosunetuzumab.
16. Women of childbearing potential must have a negative pregnancy test at screening.
17. Men must agree to use an acceptable method of contraception for the duration of the study and for 1 week after receiving the last dose of study drug.
18. Male even if surgically sterilized (i.e., status post vasectomy) must agree to 1 of the following:

* practice effective barrier contraception (e.g.: condoms) , or
* agree to practice abstinence, when this is in line with the usual lifestyle of the subject (periodic abstinence is not permitted).
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Histological diagnosis different from cFL (Campo E., 2022).
2. 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).
3. Patients with stage I or II (limited stage) suitable for RT alone treatment.
4. Prior exposure to a Bruton's tyrosine kinase (BTK) inhibitor (BTKi).
5. Prior exposure to an anti-CD20xCD3 bispecific antibody (bsAbs).
6. Need of anticoagulation with warfarin or equivalent vitamin K antagonists (e.g. phenprocoumon). Requires ongoing treatment with a strong CYP3A inducer.
7. Evidence or any history of transformation from FL to other aggressive histology.
8. Prior allogeneic hematopoietic stem cell transplantation.
9. 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
10. Life expectancy < 6 months.
11. History of progressive multifocal leukoencephalopathy (PML).
12. History of hemophagocytic lymphohistiocytosis (HLH) or chronic active EBV.
13. 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.
14. 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.
15. 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).
16. Prior treatment with chimeric antigen receptor T-cell (CAR-T) therapy within 90 days prior to first therapy administration.
17. Any uncontrolled or significant cardiovascular disease [NYHA class =2].

1. Myocardial infarction within 6 months before screening
2. Unstable angina within 3 months before screening
3. New York Heart Association class III or IV congestive heart failure
4. History of clinically significant arrhythmias (eg, sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
18. Significant history of neurologic, psychiatric, endocrinological, metabolic, immunologic, or hepatic disease that would preclude participation in the study or compromise ability to give informed consent.
19. Any history of other active malignancies within 3 years prior to study entry, except for adequately treated in situ carcinoma of the uterine cervix, basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin, non-muscle-invasive bladder cancer, localized Gleason score 6 prostate cancer, previous malignancy confined and surgically resected with curative intent.
20. Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:

1. Uncontrolled and/or active systemic infection (viral, bacterial or fungal), including active ongoing infection from SARS-CoV-2;
2. Chronic or acute hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen (Ag) negative, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from previous infection or intravenous immunoglobulins (IVIG) may participate; inactive carriers (HBsAg positive with undetectable HBV- DNA) are eligible. Patients with presence of HCV antibody are eligible only if PCR negative for HCV-RNA;
21. HIV seropositivity.
22. Pregnant or lactating women. If female, the patient is pregnant or breast-feeding.
23. Severe or debilitating pulmonary disease.
24. Unable to swallow capsules or disease significantly affecting gastrointestinal function such as malabsorption syndrome, resection of the stomach or small bowel, bariatric surgery procedures, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.
25. Underlying medical conditions that, in the investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs.
26. Major surgery within 4 weeks of the first dose of study drug.
27. Vaccination or requirement for vaccination with a live vaccine within 28 days prior to the first dose of study drug or at any time during planned study treatment.
28. Ongoing alcohol or drug addiction or any psychiatric condition(s) which would compromise ability to comply with study procedures.
29. Hypersensitivity to zanubrutinib or mosunetuzumab or any of the other ingredients of the applicable study drugs.
30. Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura).

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
23/10/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/09/2033
Actual
Sample size
Target
56
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [2] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [3] 0 0
St. Vincent Hospital Melbourne - Melbourne
Recruitment hospital [4] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 0 0
- Adelaide
Recruitment postcode(s) [2] 0 0
- Liverpool
Recruitment postcode(s) [3] 0 0
- Melbourne
Recruitment postcode(s) [4] 0 0
- Woolloongabba
Recruitment outside Australia
Country [1] 0 0
Italy
State/province [1] 0 0
Torino
Country [2] 0 0
Italy
State/province [2] 0 0
Alessandria
Country [3] 0 0
Italy
State/province [3] 0 0
Ancona
Country [4] 0 0
Italy
State/province [4] 0 0
Avellino
Country [5] 0 0
Italy
State/province [5] 0 0
Bari
Country [6] 0 0
Italy
State/province [6] 0 0
Bologna
Country [7] 0 0
Italy
State/province [7] 0 0
Brescia
Country [8] 0 0
Italy
State/province [8] 0 0
Catania
Country [9] 0 0
Italy
State/province [9] 0 0
Florence
Country [10] 0 0
Italy
State/province [10] 0 0
Milan
Country [11] 0 0
Italy
State/province [11] 0 0
Monza
Country [12] 0 0
Italy
State/province [12] 0 0
Novara
Country [13] 0 0
Italy
State/province [13] 0 0
Palermo
Country [14] 0 0
Italy
State/province [14] 0 0
Piacenza
Country [15] 0 0
Italy
State/province [15] 0 0
Reggio Emilia
Country [16] 0 0
Italy
State/province [16] 0 0
Rimini
Country [17] 0 0
Italy
State/province [17] 0 0
Roma
Country [18] 0 0
Italy
State/province [18] 0 0
Treviso

Funding & Sponsors
Primary sponsor type
Other
Name
Fondazione Italiana Linfomi - ETS
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Marco Ladetto, Prof
Address 0 0
Department of Translational Medicine of the Università degli Studi del Piemonte Orientale, Novara, Italy. AO SS Antonio e Biagio e C. Arrigo, Alessandria, Italy.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Uffici Studi FIL
Address 0 0
Country 0 0
Phone 0 0
+390131033153
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers may contact the FIL board at [email protected] 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).

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Analytic code
When will data be available (start and end dates)?
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.
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results not provided in https://clinicaltrials.gov/study/NCT06492837