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DLBCLPhase 2NCT03731234

Ibrutinib + R-CHOP Followed by Ibrutinib Maintenance

A Phase 2 study testing Ibrutinib in people with DLBCL, run by Fondazione Italiana Linfomi - ETS at 39 sites in Italy.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This is a prospective, multicenter, single arm, phase II trial in patients with ≥ 18 and <65 years with poor-prognosis (IPI ≥ 2) and newly diagnosed ABC-DLBCL. Aim of the study is to assess the efficacy and the safety of R-CHOP in combination with ibrutinib for 6 cycles followed by ibrutinib maintenance for 18 months… Read more about this study

Who is it for?
Ages 18 to 64 years
Conditions the study is for
DLBCL
What is being tested?
Ibrutinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
39 sitesItaly
Study dates
2 Jul 2019to Jul 2027
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 18 to 64 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Histologically confirmed DLBCL not otherwise specified (NOS). Patients with follicular lymphoma IIIB and large B-cell lymphoma with IRF4 rearrangement can be also included.
  • ABC type defined by Lymph2Cx on the NanoString platform. Note: A formalin fixed paraffin embedded lymph node or tumor biopsy specimen must be submitted to Central Pathology for review during the Screening Period. The specimen must have been acquired by a surgical incision or excision biopsy or from a core needle biopsy
  • Previously untreated disease
  • Age ≥ 18 and < 65 years
  • IPI score ≥ 2
  • Ann Arbor stage II-IV disease
Show all 20Show fewer
  • Measurable disease ≥ 1.5 cm in longest diameter, and measurable in 2 perpendicular dimensions
  • Normal blood count as defined as: absolute neutrophil count ≥1.0 × 10 9 /L independent of growth factor support, platelet count ≥ 100,000/mm 3 or ≥ 50,000/mm 3 if bone marrow (BM) involvement independent of transfusion support in either situation Normal organ functions defined as: creatinine ≤2 times the upper limit of normal (ULN) or estimated Glomerular Filtration Rate (Cockroft-Gault) ≥40 ml/min/1.73m 2 , aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3× the ULN; total bilirubin ≤ 1.5 × the ULN unless bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin: patients with documented Gilbert disease may be enrolled if total bilirubin is ≤ 3.0 × the ULN; International normalized ratio (INR) < 1.5 × the ULN in the absence of therapeutic anticoagulation; partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) < 1.5 × the ULN in the absence of a lupus anticoagulant
  • Patients with occult or prior hepatitis B infection (defined as HBsAg negative, anti-HBs positive and /or anti-HBc positive) may be included if hepatitis B virus (HBV) DNA is undetectable. These patients must be willing to undergo bi-monthly DNA testing and they should receive prophylaxis with Lamivudine
  • No active hepatitis C virus (HCV) infection
  • Known availability of biopsy material
  • No Central Nervous System (CNS) disease (meningeal and/or brain involvement by lymphoma)
  • Absence of active infections
  • No peripheral neuropathy or active neurological non-neoplastic disease of CNS
  • No major surgical intervention prior 3 months to enrolment if not due to lymphoma and/or no other disease life-threatening that can compromise chemotherapy treatment
  • Patient with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to the study.
  • No previous malignancies or patient with a history of curatively treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix at any time prior to the study or patients with any other malignancy in remission without treatment for at least 5 years prior to enrolment
  • Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. - Women of childbearing potential must have a negative serum (beta-human chorionic gonadotropin [Beta-hCG]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study.
  • Life expectancy > 6 months
  • Written informed consent from the patient stating understanding of the purpose and procedures required by the study and willingness to take part in the study

Who cannot join

  • DLBCL including High grade B-cell Lymphomas, both with double hit and NOS according to the 2017 Revised WHO Classification of Tumour of Haematopoietic and Lymphoid Tissues
  • GCB-DLBCL after centralized COO profiling
  • Any other histologies than DLBCL: composite or transformed disease.
  • Primary mediastinal lymphoma (PMBL)
  • Known central nervous system lymphoma
  • Primary testicular lymphoma
Show all 27Show fewer
  • Any prior lymphoma therapy
  • Contraindication to any drug in the chemotherapy regimen
  • Left ventricular ejection fraction (LVEF) < 50%
  • Neuropathy ≥ grade 2
  • Seropositive for or active viral infection with HBV
  • HBsAg positive
  • HBsAg negative, anti-HBs positive and/or anti-HBc positive with detectable viral DNA
  • Known seropositive active HCV
  • Human immunodeficiency virus (HIV) infection
  • Any of the following abnormal laboratory values (unless any of these abnormalities are due to underlying lymphoma): creatinine ≥ 2 times the ULN (unless creatinine clearance normal, or calculated creatinine clearance < 40 mL/min (using the Cockcroft-Gault formula); AST or ALT ≥3 × the ULN; total bilirubin >1.5 × the ULN: patients with documented Gilbert disease may be enrolled if total bilirubin is ≤ 3.0 × the ULN; INR > 1.5 × the ULN in the absence of therapeutic anticoagulation; PTT or aPTT > 1.5 × the ULN in the absence of a lupus anticoagulant"
  • History of stroke or intracranial hemorrhage within the past 6 months.
  • Requires anticoagulation with warfarin or equivalent vitamin K antagonists
  • Requires treatment with strong CYP3A inhibitors
  • History of clinically relevant liver or renal insufficiency; significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, rheumatologic, hematologic, psychiatric, or metabolic disturbances
  • Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification.
  • Any uncontrolled active systemic infection requiring intravenous (IV) antibiotics
  • Major surgical intervention prior 4 weeks to enrollment if not due to lymphoma and/or other disease life-threatening that can compromise chemotherapy treatment
  • Prior malignancies other than lymphoma in the last 5 years with exception of currently treated basal or squamous cell carcinoma or melanoma of the skin or in situ carcinoma of the cervix
  • Any other medical or psychological condition that might preclude participation in the study or impair the patient's ability to give informed consent.
  • Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.
  • If female, the patient is pregnant or breast-feeding

Trial locations and contacts

39 sites in 1 country.

39 sites in 1 country

Italy39 sites

  • A.O. SS. Antonio e Biagio e Cesare Arrigo - S.C. Ematologia

    Alessandria, 15121

  • Università Politecnica delle Marche- Clinica di Ematologia

    Ancona, 60121

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

    Avellino, 83100

  • Centro Riferimento Oncologico- S.O.C. Oncologia Medica A

    Aviano, 33081

  • IRCCS Istituto Tumori Giovanni Paolo II - U.O.C Ematologia

    Bari, 70121

  • ASST Spedali Civili di Brescia - Ematologia

    Brescia, 25123

  • Ospedale Businco - SC Ematologia e CTMO

    Cagliari, 09121

  • Ospedale di Castelfranco Veneto - Oncoematologia IOV

    Castelfranco Veneto, Treviso, 31033

  • Arnas Nuovo Ospedale Garibaldi Nesima - U.O.C. Ematologia

    Catania, 95123

  • Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia

    Florence, 50141

  • Ospedale Policlinico San Martino S.S.R.L- IRCCS per l'Oncologia - Ematologia

    Genova, 16132

  • Azienda Ospedali Riuniti Papardo-Piemonte - S.C. Ematologia

    Messina, 98158

  • Istituto Scientifico San Raffaele - Unità Linfomi - Dipartimento Oncoematologia

    Milan, 20132

  • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano - Ematologia

    Milan, 20133

  • IEO Istitito Europeo di Oncologia - Divisione Ematoncologia

    Milan, 20141

  • ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia

    Milan, 20162

  • Azienda Ospedaliero-Universitaria Policlinico di Modena - Ematologia

    Modena, 41123

  • Monza - Fondazione IRCCS San Gerardo dei Tintori - Ematologia

    Monza, 20900

  • Istituto Nazionale Tumori - IRCCS Fondazione G. Pascale - UOC Ematologia Oncologica

    Naples, 80131

  • AOU Maggiore della Carità di Novara - SCDU Ematologia

    Novara, 28100

  • I.R.C.C.S. Istituto Oncologico Veneto - Oncologia 1

    Padova, 35128

  • IRCCS Policlinico S. Matteo di Pavia - Div. di Ematologia

    Pavia, 27100

  • P.O. Spirito Santo di Pescara - UOS Dipartimentale - Centro di diagnosi e Terapia dei linfomi

    Pescara, 65124

  • Ospedale Guglielmo da Saliceto - U.O.Ematologia

    Piacenza, 29121

  • AOU Pisana - U.O. Ematologia

    Pisa, 56126

  • A.O.R. "San Carlo" - U.O. Ematologia

    Potenza, 85100

  • Ospedale delle Croci - Ematologia

    Ravenna

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

    Reggio Emilia, 42123

  • Ospedale degli Infermi di Rimini - U.O. di Ematologia

    Rimini, 47923

  • Dipartimento di Medicina Traslazionale e di Precisione, Università 'La Sapienza'

    Roma

  • Università Cattolica S. Cuore - Ematologia

    Roma

  • Casa Sollievo della Sofferenza - UO Ematologia

    San Giovanni Rotondo

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

    Terni

  • A.O.U. Citta della Salute e della Scienza di Torino - Centro Ematologia Universitaria

    Torino, 10126

  • A.O.U. Citta della Salute e della Scienza di Torino - S.C.Ematologia

    Torino, 10126

  • A.O. C. Panico - U.O.C Ematologia e Trapianto

    Tricase, 73039

  • Azienda Sanitaria Universitaria Integrata Trieste (ASUITS) SC Ematologia

    Trieste

  • Ospedale Azienda Sanitaria Universitaria Integrata di Udine (A.S.U.I. Udine)-SOC Clinica Ematologica

    Udine, 33100

  • Ospedale di Circolo U.O.C Ematologia

    Varese

Other trials in Italy

About this study

Official title: Phase II Multicenter Single Arm Study to Evaluate the Efficacy and Safety of Ibrutinib in Combination to Rituximab-CHOP Followed by Ibrutinib Maintenance in Untreated Patients With Activated-B-Cell (ABC)-DLBCL at Intermediate-high and High Risk (IPI ≥2)

This is a prospective, multicenter, single arm, phase II trial in patients with ≥ 18 and <65 years with poor-prognosis (IPI ≥ 2) and newly diagnosed ABC-DLBCL.

Aim of the study is to assess the efficacy and the safety of R-CHOP in combination with ibrutinib for 6 cycles followed by ibrutinib maintenance for 18 months in ABC-DLBCL patients achieving at least a PR after the induction phase

Read the detailed description

Step 1 - Screening phase If central review will confirm and define the diagnosis of ABC-DLBCL according the COO, eligible patients will have to sign an additional informed consent prior to receive the study subsequent treatment.

Step 2 - study treatment phases Induction phase: 5 courses of R-CHOP every 21 days combined with ibrutinib (560 mg/day, continuously).

Maintenance phase: patients achieving a CR or a PR after 5 courses of RI-CHOP21 will enter the maintenance phase with ibrutinib (560 mg/day, continuously) for 18 months.

Radiotherapy could be delivered as consolidation treatment at the end of R-chemotherapy, according to Institution local clinical practice, in patients with focal PET positive residual disease and to bone extranodal lesions or scrotum, if testicular involvement irrespective of initial tumor diameter.

Conditions
DLBCL
Being tested
Ibrutinib
Keywords
DLBCL, Activated-B-Cell DLBCL, Ibrutinib, Phase II

What participants receive

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

  • IbrutinibDrug

    Also called IMBRUVICA (commercial name)

    Ibrutinib in combination to rituximab-CHOP followed by ibrutinib maintenance

Study groups in NCT03731234
Study groupRoleWhat they receive
Ibrutinib+R-CHOPExperimentalScreening phase for selection of Activated-B-Cell (ABC)-DLBCL Induction phase: R-CHOP21 x 5 cycles in combination with ibrutinib Maintenance phase: maintenance with Ibrutinib for 18 months for patients responding to the induction phase (CR or PR)
Receives: Drug: Ibrutinib

What is being measured

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

  1. Progression-free survival (PFS) (1st time point of assessment)

    PFS of the high/high-intermediate risk patients from date of enrolment

    Measured: Time between the date of enrolment and the date of disease progression, relapse or death from any cause (24 months)

  2. Progression-free survival (PFS) (2nd time point of assessment)

    PFS of the high/high-intermediate risk patients from date of enrolment

    Measured: Time between the date of enrolment and the date of disease progression, relapse or death from any cause (36 months)

  3. Progression-free survival (PFS) (3dr time point of assessment)

    PFS of the high/high-intermediate risk patients from date of enrolment

    Measured: Time between the date of enrolment and the date of disease progression, relapse or death from any cause (48 months)

Secondary outcomes (5)

  1. Overall Survival (OS)

    Overall Survival

    Measured: Time between the date of enrolment and the date of death from any cause (24, 36 and 48 months).

  2. Complete response and Overall Response (CR+PR) rate at the end of induction

    Complete response and Overall Response

    Measured: End of induction (EOI) (4 months)

  3. Duration of response (DOR)

    Duration of response

    Measured: From the date when criteria for response are met (CR or PR) until the date of progression or relapse. Patients without relapse or progression or death from other causes will be censored at their last assessment date (24 months from response date)

  4. Complete remission (CRR) after ibrutinib maintenance

    Complete remission after ibrutinib maintenance

    Measured: End of treatment (EOT) (up to 24 months)

  5. Event Free Survival (EFS)

    Event Free Survival

    Measured: From the date of enrolment to the date of disease progression, relapse from CR, initiation of subsequent systemic anti-lymphoma therapy after the least 6 cycles of RI-CHOP (each cycle is 21 days), or death whichever occurs first (24, 36 and 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 Nov 2018
  2. Study start2 Jul 2019
  3. Primary completion30 Jul 2024
  4. Study completionJul 2027 (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
Ibrutinib in combination to rituximab-CHOP followed by ibrutinib maintenance
Masking
None (open label)
Enrolment
75 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03731234
Sponsor's protocol ID
FIL_RI-CHOP
Status last verified
Sep 2026
First submitted
4 Oct 2018
Last updated
8 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ibrutinib in people with DLBCL, run by Fondazione Italiana Linfomi - ETS at 39 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 20 inclusion and 27 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: under way, not looking for participants, as of the sponsor's last update on 8 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 39 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?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free survival (PFS) (1st time point of assessment) (time frame: Time between the date of enrolment and the date of disease progression, relapse or death from any cause (24 months)). The study lists 3 primary outcomes in all. 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 NCT03731234.

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 8 Sep 2026.

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