AzTrials
AzTrials

Mantle Cell LymphomaPhase 2FIL_PUMANCT07207785

PirtobrUtinib as Frontline Therapy for Elderly Unfit/Frail Patient With MAntle Cell Lymphoma

A Phase 2 study testing Pirtobrutinib in people with Mantle Cell Lymphoma, run by Fondazione Italiana Linfomi - ETS at 20 sites in Italy.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 70 years and older
Conditions the study is for
Mantle Cell Lymphoma
What is being tested?
Pirtobrutinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
20 sitesItaly
Study dates
1 Feb 2026to 1 Feb 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 70 years and older
  • All sexes
  • No healthy volunteers
  • Older adult

Who may be able to join

  • 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)
Show all 41Show fewer
  • 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
  • IADL 8 residual functions and
  • CIRS 0 comorbidities of grade 3-4 and <5 comorbidities of grade 2
  • or
  • Age < 80 years:
  • ADL < 5 residual functions and/or
  • IADL < 6 residual functions and/or
  • CIRS ≥ 1 comorbidity of grade 3-4 or >8 comorbidities of grade 2
  • Ann Arbor Stage I - IV
  • At least one bi-dimensionally measurable lesion defined as > 1.5 cm in its largest dimension on CT scan
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0- 2
  • Adequate hematologic function (unless caused by bone marrow infiltrate), defined as follows:
  • Hemoglobin ≥ 8 g/dL (independent of transfusions within 7 days of screening assessment)
  • White blood cells (WBC) > 2500/mmc with polymorphonuclear (cells) PMN≥750/ mmc) (independent of growth factor support within 7 days of screening assessment)
  • Platelets count ≥ 50000/mmc (independent of transfusions within 7 days of screening assessment)
  • Adequate renal function:
  • Creatinine clearance ≥ 30 mL/min or
  • Serum creatinine ≤ 2.5 mg /dL
  • Adequate coagulation, defined as activated partial thromboplastin time (aPTT) or partial thromboplastin time (PTT) and prothrombin (PT) or (international normalized ratio (INR) not greater than 1.5 x upper limit of normal (ULN)
  • Adequate hepatic function:
  • Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≤ 3 x the ULN or ≤ 5 x ULN with documented liver involvement
  • Total bilirubin ≤ 1.5 x ULN or ≤ 3 x ULN with documented liver involvement and/or due to Gilbert's Disease
  • Ability and willingness to comply with the study protocol procedure
  • Life expectancy > 6 months
  • The patient is able to take oral medications
  • The patient must give written informed consent
  • Male subjects must use highly effective contraception during sexual contact with a pregnant female or a female of childbearing potential from the start of study treatment and continuing for at least 3 months after the last dose of pirtobrutinib

Who cannot join

  • 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
Show all 41Show fewer
  • 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)
  • History of stroke or intracranial hemorrhage within 6 months of investigation treatment
  • History of Chimeric Antigen Receptor T-cell therapy (CAR-T) within 60 days of investigation treatment or presence of any of the following, regardless of prior Stem Cell Transplantation (SCT) and/or CAR-T therapy timing:
  • active graft versus host disease (GVHD);
  • cytopenia from incomplete blood cell count recovery post-transplant;
  • need for anti-cytokine therapy for toxicity from CAR-T therapy; residual symptoms of neurotoxicity > Grade 1 from CAR-T therapy;
  • ongoing immunosuppressive therapy (> 20 mg prednisone or equivalent daily)
  • Evidence of any severe active acute or chronic infection
  • Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, HCV-RNA is required. Only patients with HCV-RNA negative are accepted.
  • Known active cytomegalovirus (CMV) infection. Unknown or negative status are eligible
  • Clinically significant active malabsorption syndrome or other conditions likely to affect gastrointestinal (GI) absorption of the study drug
  • Evidence of other clinically significant uncontrolled condition(s) including but not limited to, uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the investigator and medical monitor may pose a risk for patient participation. Screening for chronic conditions is not required
  • Active uncontrolled auto-immune cytopenia (e.g., AutoImmune Hemolytic Anemia [AIHA], Idiopathic Thrombocytopenic Purpura [ITP]) for which new therapy was introduced or existing therapy was escalated within the 4 weeks prior to study enrollment to maintain adequate blood counts
  • Significant cardiovascular disease defined as:
  • unstable angina or acute coronary syndrome within the past 2 months prior to study enrollment
  • history of myocardial infarction within 3 months prior to study enrollment or
  • documented left ventricular ejection fraction (LVEF) by any method of ≤ 40% in the 12 months prior to study enrollment
  • ≥ Grade 3 New York Heart Association (NYHA) functional classification system of heart failure
  • Uncontrolled or symptomatic arrhythmias
  • Prolongation of the QT interval corrected for heart rate (QTcF) > 470 msec. QTcF is calculated using Fridericia's Formula (QTcF): QTcF = QT/(RR0.33):
  • Correction of suspected drug-induced QTcF prolongation can be attempted at the investigator's discretion and only if clinically safe to do so with either discontinuation of the offending drug or switch to another drug not known to be associated with QTcF prolongation.
  • Correction for underlying bundle branch block (BBB) allowed. Note: Patients with pacemakers are eligible if they have no history of fainting or clinically relevant arrhythmias while using the pacemaker
  • Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
  • Absence of caregivers in non-autonomous patients
  • Need of anticoagulation with warfarin or another vitamin K antagonist
  • Vaccination with live vaccine within 28 days prior to investigation treatment
  • Have a known hypersensitivity to any of the excipients of Pirtobrutinib or to any intended study medications

Trial locations and contacts

20 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Uffici Studi FIL contact

+390599769918

startup@filinf.it

Uffici Studi FIL contact

+390599769911

gestionestudi@filinf.it

20 sites in 1 country

Italy20 sites

  • AOU Ospedali Riuniti - Clinica di Ematologia

    Ancona

    Guido Gini, MD, guido.gini@ospedaliriuniti.marche.it

    Guido Gini, MD

  • Azienda Ospedaliera S.Giuseppe Moscati - S.C. Ematologia e Trapianto emopoietico

    Avellino

    Sonya De Lorenzo, MD, sonya.delorenzo@tin.it

    Sonya De Lorenzo, MD

  • Nuovo Ospedale degli Infermi - SSD Ematologia

    Biella

    Annarita Conconi, MD, annarita.conconi@aslbi.piemonte.it

    Annarita Conconi, MD

  • Policlinico S.Orsola-Malpighi - Istituto di Ematologia "Seragnoli"

    Bologna

    Pier Luigi Zinzani, Prof., pierluigi.zinzani@unibo.it

    Pier Luigi Zinzani, Prof.

  • ASST Spedali Civili di Brescia - Ematologia

    Brescia

    Chiara Pagani, MD, chiara.pagani@asst-spedalicivili.it

    Chiara Pagani, MD

  • Azienda Ospedaliera Universitaria Policlinico - S. Marco - UOC di Ematologia

    Catania

    Annalisa Chiarenza, MD, annalisa.chiarenza@gmail.com

    Annalisa Chiarenza, MD

  • IRCCS Istituto Romagnolo per lo studio dei Tumori "Dino Amadori" - IRST S.R.L. - Ematologia

    Meldola, Forlì-Cesena

    Margherita Parolini, MD, margherita.parolini@irst.emr.it

    Margherita Parolini, MD

  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano - Ematologia

    Milan

    Lucia Farina, MD, lucia.farina@istitutotumori.mi.it

    Lucia Farina, MD

  • A.O. Ospedali Riuniti Villa Sofia-Cervello - Divisione di Ematologia

    Palermo

    Caterina Patti, MD, k.patti@villasofia.it

    Caterina Patti, MD

  • Parma - AOU di Parma - UOC Ematologia e CTMO

    Parma

    Giovanni Roti, Prof., giovanni.roti@unipr.it

    Giovanni Roti, Prof.

  • P.O. Spirito Santo di Pescara - UOC Ematologia Dipartimento Oncologico Ematologico - ASL Pescara

    Pescara

    Elsa Pennese, MD, elsa.pennese@asl.pe.it

    Elsa Pennese, MD

  • Azienda USL Piacenza - UOC Ematologia e Centro Trapianti

    Piacenza

    Annalisa Arcari, MD, a.arcari@ausl.pc.it

    Annalisa Arcari, MD

  • Azienda Unitа Sanitaria Locale-IRCCS - Arcispedale Santa Maria Nuova - Ematologia

    Reggio Emilia

    Angela Ferrari, MD, ferrari.angela@ausl.re.it

    Angela Ferrari, MD

  • Istituto Clinico Humanitas - U.O. Ematologia

    Rozzano, Milano

    Monica Balzarotti, MD, monica.balzarotti@humanitas.it

    Monica Balzarotti, MD

  • AOU Senese - U.O.C. Ematologia

    Siena

    Alberto Fabbri, MD, fabbri7@unisi.it

    Alberto Fabbri, MD

  • A.O. S. Maria di Terni - S.C. Oncoematologia

    Terni

    Arcangelo Liso, Prof., arcangelo.liso@unipg.it

    Arcangelo Liso, Prof.

  • Ospedale Ca Foncello - S.C di Ematologia

    Treviso

    Piero Maria Stefani, MD, pieromaria.stefani@aulss2.veneto.it

    Piero Maria Stefani, MD

  • Ospedale di Circolo - U.O.C Ematologia

    Varese

    Marta Coscia, Prof.

    Marta Coscia, Prof.

  • AOU Integrata di Verona - U.O. Ematologia

    Verona

    Carlo Visco, Prof., carlo.visco@univr.it

    Carlo Visco, Prof.

  • Vicenza - ULSS 8 Berica - Ospedale S. Bortolo - Ematologia

    Vicenza

    Maria Chiara Tisi, MD, mariachiara.tisi@aulss8.veneto.it

    Maria Chiara Tisi, MD

Other trials in Italy

About this study

Official title: PirtobrUtinib as Frontline Therapy for Elderly Unfit/Frail Patient With MAntle Cell Lymphoma: a Phase II Study of the Fondazione Italiana Linfomi (FIL)

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.

Read the detailed description

After providing written informed consent, patients will be evaluated for eligibility during a 28-day screening period. Patients will receive pirtobrutinib at a starting dose of 200 mg once daily (2 tablets 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.

Responses shall be assessed at month +3, +6 after start of treatment and then every 6 months using the radiologic method of tumor assessment consistent throughout the study and aligned with the baseline method (CT scan or ultrasound echography are acceptable). Positron Emission Tomography (PET) scan is mandatory at baseline and at month +3 after start of treatment to establish tumor response.

Being tested
Pirtobrutinib
Keywords
mantle cell lymphoma, unfit, frail, monotherapy, pirtobrutinib, Jaypirca
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PirtobrutinibDrug

    Also called Jaypirca

    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.

Study groups in NCT07207785
Study groupRoleWhat they receive
ExperimentalExperimentalPirtobrutinib monotherapy in untreated elderly unfit/frail MCL patients.
Receives: Drug: Pirtobrutinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: 48 months

Secondary outcomes (10)

  1. Overall response rate (ORR)

    Overall Response Rate (ORR) will be defined as the proportion of patients achieving either a Complete Response (CR) or a Partial Response (PR), according to the Lugano 2014 criteria for response assessment in lymphoma.

    Measured: 48 months

  2. Complete response rate (CRR)

    Complete response rate (CRR) refers to the proportion of patients whose disease completely disappears following treatment, as determined by clinical, imaging, or pathological assessments. It indicates a full remission of detectable disease.

    Measured: 48 months

  3. Overall survival (OS)

    Overall survival (OS) is defined as the time between the start of treatment and death from any cause

    Measured: 48 months

  4. Event free survival (EFS)

    Event free survival (EFS) is defined as the time between the start of treatment and treatment failure including disease progression, or discontinuation of treatment for any reason (e.g., disease progression, toxicity, patient preference, initiation of new treatment without documented progression, or death).

    Measured: 48 months

  5. Duration of response (DOR)

    Duration of response (DOR) is defined as the time from the first documentation of tumor response to disease progression or death from any cause.

    Measured: 48 months

  6. Drop-out rate

    Proportion of participants who withdraw from the study for any reason before completing the planned treatment/intervention period.

    Measured: 48 months

  7. Rate of treatment discontinuation due to Adverse Event (AE) or treatment intolerance.

    Proportion of participants who permanently discontinue the assigned treatment due to adverse events (AEs) or treatment intolerance during the study period.

    Measured: 48 months

  8. Frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)

    Frequency and severity of AEs and SAEs classified as per latest version of CTCAE

    Measured: 48 months

  9. Health-Related Quality of Life Assessed by the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Questionnaire

    The EQ-5D-5L is a standardized instrument for measuring generic health status. It includes five dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each with five levels. The outcome will be reported as the EQ-5D-5L index score. Higher scores indicate better health status.

    Measured: 48 months

  10. Health-Related Quality of Life Assessed by the Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) Questionnaire

    The FACT-Lym is a disease-specific instrument assessing quality of life in patients with lymphoma. It includes physical, social/family, emotional, and functional well-being, plus lymphoma-specific concerns. The outcome will be reported as the total FACT-Lym score. Higher scores indicate better quality of life.

    Measured: 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Oct 2025
  2. Study start1 Feb 2026 (estimated)
  3. Primary completion1 Feb 2028 (estimated)
  4. Study completion1 Feb 2030 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
This is a one-arm phase II study, with a hypothesis of superior efficacy compared to usual/standard clinical approaches.
Masking
None (open label)
Enrolment
56 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07207785
Sponsor's protocol ID
FIL_PUMA
Acronym
FIL_PUMA
Status last verified
Sep 2025
First submitted
17 Sep 2025
Last updated
6 Oct 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: 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.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pirtobrutinib in people with Mantle Cell Lymphoma, run by Fondazione Italiana Linfomi - ETS at 20 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 41 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 6 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Uffici Studi FIL (+390599769918, startup@filinf.it), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: 48 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07207785.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Oct 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in