PirtobrUtinib as Frontline Therapy for Elderly Unfit/Frail Patient With MAntle Cell Lymphoma
FIL_PUMA
1 other identifier
interventional
56
1 country
20
Brief Summary
This is a prospective, multicenter, phase II study, in elderly patients affected by Mantle cell lymphoma (MCL) defined as unfit/frail according to Simplified Geriatric Assessment (sGA) and previously untreated. Patients will receive a treatment with Pirtobrutinib monotherapy until tumor progression, unacceptable adverse event, or patient decision for interruption.
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 Feb 2026
Typical duration for phase_2
20 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 17, 2025
CompletedFirst Posted
Study publicly available on registry
October 6, 2025
CompletedStudy Start
First participant enrolled
February 1, 2026
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 1, 2030
October 6, 2025
September 1, 2025
2 years
September 17, 2025
September 26, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Progression Free Survival (PFS)
PFS defined as the time between the start of treatment and the first documentation of recurrence, progression or death for any cause
48 months
Secondary Outcomes (10)
Overall response rate (ORR)
48 months
Complete response rate (CRR)
48 months
Overall survival (OS)
48 months
Event free survival (EFS)
48 months
Duration of response (DOR)
48 months
- +5 more secondary outcomes
Study Arms (1)
Experimental
EXPERIMENTALPirtobrutinib monotherapy in untreated elderly unfit/frail MCL patients.
Interventions
Patients will receive pirtrobrutinib at a starting dose of 200 mg once daily (q.d). All treatment will be administered orally and a cycle will be defined as 28 days in length and should be maintained regardless of dose interruptions. Treatment is meant to be administered until tumor progression, unacceptable adverse event, or patient decision for interruption.
Eligibility Criteria
You may qualify if:
- Histologically documented diagnosis of nodal and extranodal mantle cell lymphoma (MCL) as defined in the 2022 edition of the World Health Organization (WHO) classification
- Availability of biopsy material for central pathology revision and mutational analysis including TP53 (Tumor Protein p53) mutations
- Age ≥ 70 years
- Previously untreated MCL
- Active disease in need of treatment according to clinical practice (patients with leukemic with symptomatic leukemic non nodal disease may be included)
- Ineligible to standard full-dose induction therapy (i.e. BR, R-CHOP, VR-CAP, RBAC500)
- sGA assessment performed before starting treatment
- FRAIL patients defined as follows:
- Age ≥ 80 years
- Activities of Daily Living (ADL) \<6 residual functions and/or
- Instrumental Activities of Daily Living (IADL) \<8 residual functions and/or
- Cumulative Illness Rating Scale (CIRS): ≥ 1 comorbidity of grade 3-4 or ≥ 5 comorbidities of grade 2
- UNFIT patients defined as follows:
- Age ≥ 80 years:
- ADL 6 residual functions and
- +25 more criteria
You may not qualify if:
- Patients who meet any of the following criteria are not eligible to enroll:
- Candidate to watch and wait due to indolent presentation
- Leukemic non-nodal MCL that has stable asymptomatic disease should not be included in this study
- Histological diagnosis different from MCL or leukemic non-nodal MCL
- Fit patients according to sGA eligible to standard full dose therapy
- Candidate or eligible to full-dose Bendamustine+Rituximab (BR), Rituximab + Cyclophosphamide, Hydroxydaunorubicin (doxorubicin), Oncovin (vincristine) e Prednisone (R-CHOP), bortezomib, rituximab, cyclophosphamide, doxorubicin, prednisone (VR-CAP), Rituximab, Bendamustine, Cytarabine (RBAC500) or any other full dose intensive chemotherapy
- Suspect or clinical evidence of central nervous system (CNS) involvement by lymphoma
- Contraindication to the use Bruton Tyrosine Kinase Inhibitor (BTKi)
- HBsAg positivity; HBsAg-negative patients with anti-hepatitis B core antigen (HBc) antibody can be enrolled if Hepatitis B Virus (HBV)-DNA are negative and prophylactic antiviral treatment is provided
- HIV positivity
- Active herpes zoster infection; previously infected patients is accepted only with concomitant treatment with Valacyclovir
- Major surgery within 4 weeks prior to investigation treatment
- Any history of other malignancies unless in remission and with life expectancy \> 2 years prior to study entry except for adequately treated carcinoma in situ of the cervix or basal or squamous cell skin cancer
- Patients who experienced grade ≥ 3 arrhythmia.
- History of severe bleeding diathesis (major bleeding event) Note: Major bleeding is defined as bleeding having one or more of the following features: potentially life-threatening bleeding with signs or symptoms of hemodynamic compromise; bleeding associated with a decrease in the hemoglobin level of at least 2 g per deciliter; or bleeding in a critical area or organ (e.g., retroperitoneal, intraarticular, pericardial, epidural, or intracranial bleeding or intramuscular bleeding with compartment syndrome)
- +26 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (20)
IRCCS Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" - IRST S.R.L. - Ematologia
Meldola, Forlì-Cesena, Italy
Istituto Clinico Humanitas - U.O. Ematologia
Rozzano, Milano, Italy
AOU Ospedali Riuniti - Clinica di Ematologia
Ancona, Italy
Azienda Ospedaliera S.Giuseppe Moscati - S.C. Ematologia e Trapianto emopoietico
Avellino, Italy
Nuovo Ospedale degli Infermi - SSD Ematologia
Biella, 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
Fondazione IRCCS Istituto Nazionale dei Tumori di Milano - Ematologia
Milan, Italy
A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia
Palermo, Italy
Parma - AOU di Parma - UOC Ematologia e CTMO
Parma, Italy
P.O. Spirito Santo di Pescara - UOC Ematologia Dipartimento Oncologico Ematologico - ASL Pescara
Pescara, Italy
Azienda USL Piacenza - UOC Ematologia e Centro Trapianti
Piacenza, Italy
Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia
Reggio Emilia, Italy
AOU Senese - U.O.C. Ematologia
Siena, Italy
A.O. S. Maria di Terni - S.C. Oncoematologia
Terni, Italy
Ospedale Ca Foncello - S.C di Ematologia
Treviso, Italy
Ospedale di Circolo - U.O.C Ematologia
Varese, Italy
AOU Integrata di Verona - U.O. Ematologia
Verona, Italy
Vicenza - ULSS 8 Berica - Ospedale S. Bortolo - Ematologia
Vicenza, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Carlo Visco, Prof.
Verona - AOU Integrata di Verona - U.O. Ematologia
- PRINCIPAL INVESTIGATOR
Guido Gini, Dott.
Ancona - AOU Ospedali Riuniti - Clinica di Ematologia
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
September 17, 2025
First Posted
October 6, 2025
Study Start
February 1, 2026
Primary Completion (Estimated)
February 1, 2028
Study Completion (Estimated)
February 1, 2030
Last Updated
October 6, 2025
Record last verified: 2025-09
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, individual deidentified 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.
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. 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. In compliance with the national ethics guideline and applicable legislation, individual deidentified patients' data (including study protocol, statistical analysis plan and data coding) can be shared until 5 years after the publication of the study.