Trial Title:
Study With Mosunetuzumab and Zanubrutinib in R/R Follicular Lymphoma Patients
NCT ID:
NCT06492837
Condition:
Follicular Lymphoma
Conditions: Official terms:
Lymphoma
Lymphoma, Follicular
Zanubrutinib
Conditions: Keywords:
Follicular lymphoma
Mosunetuzumab
Zanubrutinib
Relapsed/refractory follicular lymphoma
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Mosunetuzumab in combination with Zanubrutinib
Description:
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.
Arm group label:
Mosunetuzumab in combination with Zanubrutinib
Other name:
LUNSUMIO in combination with BRUSINKA
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.
Detailed description:
Eligible patients receive a pre-phase with oral zanubrutinib followed by an induction
phase with mosunetuzumab combined with oral zanubrutinib.
Patients responsive to induction phase with M+Z (C1-12) and achieving at least SD will
receive maintenance with zanubrutinib for additional 12 months (C13-24).
There will be an initial safety run-in (SRI) phase of 10 patients which will be closely
monitored for the observed toxicities during the first three cycles of induction (from
C1D1 to C3D28). No patients will be further enrolled until SRI analyses is completed.
If no unexpected toxicity has been observed, subsequent patients will be monitored only
for patient informed consent, grade 3-5 toxicities and SAEs as well as remission status.
Safety data will be evaluated by an independent data safety monitoring board (DSMB) that
will advise the principal investigators on the continuation of the study. Safety events
will be analyzed and compared with the previously described safety profile of
mosunetuzumab alone and other bispecific-containing regimens to exclude the risk of
potential toxicity for all study participants.
Criteria for eligibility:
Criteria:
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).
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).
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Fondazione del Piemonte per l'Oncologia - IRCCS, Ematologia
Address:
City:
Candiolo
Country:
Italy
Contact:
Last name:
Francesca Bonello
Email:
francesca.bonello@ircc.it
Investigator:
Last name:
Francesca Bonello, MD
Email:
Principal Investigator
Facility:
Name:
AOU SS. Antonio e Biagio e Cesare Arrigo, SCDU Ematologia
Address:
City:
Alessandria
Country:
Italy
Contact:
Last name:
Marco Ladetto, Prof
Email:
marco.ladetto@uniupo.it
Investigator:
Last name:
Marco Ladetto, Prof
Email:
Principal Investigator
Facility:
Name:
AOU Ospedali Riuniti, Clinica di Ematologia
Address:
City:
Ancona
Country:
Italy
Contact:
Last name:
Guido Gini, MD
Email:
guido.gini@ospedaliriuniti.marche.it
Investigator:
Last name:
Guido Gini, MD
Email:
Principal Investigator
Facility:
Name:
Azienda Ospedaliera S.Giuseppe Moscati, S.C. Ematologia e Trapianto emopoietico
Address:
City:
Avellino
Country:
Italy
Contact:
Last name:
Sonya De Lorenzo, MD
Email:
sonya.delorenzo@tin.it
Investigator:
Last name:
Sonya De Lorenzo, MD
Email:
Principal Investigator
Facility:
Name:
IRCCS Istituto Tumori Giovanni Paolo II, U.O.C Ematologia
Address:
City:
Bari
Country:
Italy
Contact:
Last name:
Attilio Guarini, MD
Email:
attilioguarini@oncologico.bari.it
Investigator:
Last name:
Attilio Guarini, MD
Email:
Principal Investigator
Facility:
Name:
Policlinico S.Orsola-Malpighi, Istituto di Ematologia "Seragnoli"
Address:
City:
Bologna
Country:
Italy
Contact:
Last name:
Pier Luigi Zinzani, Prof
Email:
pierluigi.zinzani@unibo.it
Investigator:
Last name:
Pier Luigi Zinzani, Prof
Email:
Principal Investigator
Facility:
Name:
ASST Spedali Civili di Brescia, Ematologia
Address:
City:
Brescia
Country:
Italy
Contact:
Last name:
Antonella Anastasia, MD
Email:
antonella.anastasia@gmail.com
Investigator:
Last name:
Antonella Anastasia, MD
Email:
Principal Investigator
Facility:
Name:
Azienda Ospedaliera Universitaria Policlinico - S. Marco, UOC di Ematologia
Address:
City:
Catania
Country:
Italy
Contact:
Last name:
Annalisa Chiarenza, MD
Email:
annalisa.chiarenza@gmail.com
Investigator:
Last name:
Annalisa Chiarenza, MD
Email:
Principal Investigator
Facility:
Name:
Azienda Ospedaliera Universitaria Careggi, Unità funzionale di Ematologia
Address:
City:
Firenze
Country:
Italy
Contact:
Last name:
Luca Nassi, MD
Email:
nassil@aou-careggi.toscana.it
Investigator:
Last name:
Luca Nassi, MD
Email:
Principal Investigator
Facility:
Name:
ASST Grande Ospedale Metropolitano Niguarda, SC Ematologia
Address:
City:
Milano
Country:
Italy
Contact:
Last name:
Vittorio Ruggero Zilioli, MD
Email:
vittorioruggero.zilioli@ospedaleniguarda.it
Investigator:
Last name:
Vittorio Ruggero Zilioli, MD
Email:
Principal Investigator
Facility:
Name:
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Ematologia
Address:
City:
Milano
Country:
Italy
Contact:
Last name:
Paolo Corradini, Prof
Email:
paolo.corradini@unimi.it
Investigator:
Last name:
Paolo Corradini, Prof
Email:
Principal Investigator
Facility:
Name:
Fondazione IRCCS San Gerardo dei Tintori, Ematologia
Address:
City:
Monza
Country:
Italy
Contact:
Last name:
Silvia Bolis, MD
Email:
silviaanna.bolis@irccs-sangerardo.it
Investigator:
Last name:
Silvia Bolis, MD
Email:
Principal Investigator
Facility:
Name:
AOU Maggiore della Carità di Novara, SCDU Ematologia
Address:
City:
Novara
Country:
Italy
Contact:
Last name:
Gloria Margiotta Casaluci, MD
Email:
gloria.margiotta@med.uniupo.it
Investigator:
Last name:
Gloria Margiotta Casaluci, MD
Email:
Principal Investigator
Facility:
Name:
A.O. Ospedali Riuniti Villa Sofia-Cervello, Divisione di Ematologia
Address:
City:
Palermo
Country:
Italy
Contact:
Last name:
Caterina Patti, MD
Email:
k.patti@villasofia.it
Investigator:
Last name:
Caterina Patti, MD
Email:
Principal Investigator
Facility:
Name:
Azienda USL Piacenza, UOC Ematologia e Centro Trapianti
Address:
City:
Piacenza
Country:
Italy
Contact:
Last name:
Annalisa Arcari, MD
Email:
a.arcari@ausl.pc.it
Investigator:
Last name:
Annalisa Arcari, MD
Email:
Principal Investigator
Facility:
Name:
Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova, Ematologia
Address:
City:
Reggio Emilia
Country:
Italy
Contact:
Last name:
Stefano Luminari, Prof
Email:
stefano.luminari@ausl.re.it
Investigator:
Last name:
Stefano Luminari, Prof
Email:
Principal Investigator
Facility:
Name:
Ospedale degli Infermi di Rimini, U.O. di Ematologia
Address:
City:
Rimini
Country:
Italy
Contact:
Last name:
Melania Celli, MD
Email:
melania.celli@auslromagna.it
Investigator:
Last name:
Melania Celli, MD
Email:
Principal Investigator
Facility:
Name:
Policlinico Umberto I - Università La Sapienza, Istituto Ematologia, Dipartimento di Medicina Traslazionale e di Precisione
Address:
City:
Roma
Country:
Italy
Contact:
Last name:
Ilaria Del Giudice, Prof
Email:
ilaria.delgiudice@uniroma1.it
Investigator:
Last name:
Ilaria Del Giudice, MD
Email:
Principal Investigator
Facility:
Name:
A.O.U. Città della Salute e della Scienza di Torino, S.C.Ematologia
Address:
City:
Torino
Country:
Italy
Contact:
Last name:
Carola Boccomini, MD
Email:
cboccomini@cittadellasalute.to.it
Investigator:
Last name:
Carola Boccomini, MD
Email:
Principal Investigator
Facility:
Name:
Ospedale Ca' Foncello, S.C di Ematologia
Address:
City:
Treviso
Country:
Italy
Contact:
Last name:
Piero Maria Stefani, MD
Email:
pieromaria.stefani@aulss2.veneto.it
Investigator:
Last name:
Piero Maria Stefani, MD
Email:
Principal Investigator
Start date:
September 15, 2024
Completion date:
September 15, 2033
Lead sponsor:
Agency:
Fondazione Italiana Linfomi - ETS
Agency class:
Other
Source:
Fondazione Italiana Linfomi - ETS
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06492837
