Ibrutinib + R-CHOP Followed by Ibrutinib Maintenance

NCT03731234 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: FIL_RI-CHOP
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 39

Brief 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 in ABC-DLBCL patients achieving at least a PR after the induction phase

Conditions

DLBCL

Keywords

DLBCL; Activated-B-Cell DLBCL; Ibrutinib; Phase II

Outcome Measures

Primary Outcomes (3)

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

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

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

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

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

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

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

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

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

Secondary Outcomes (5)

• Overall Survival (OS)

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

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

  End of induction (EOI) (4 months)

• Duration of response (DOR)

  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)

• Complete remission (CRR) after ibrutinib maintenance

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

• Event Free Survival (EFS)

  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)

Study Arms (1)

Ibrutinib+R-CHOP

EXPERIMENTAL

Screening 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)

Drug: Ibrutinib

Interventions

Ibrutinib DRUG

Ibrutinib in combination to rituximab-CHOP followed by ibrutinib maintenance

Also known as: IMBRUVICA (commercial name)

Ibrutinib+R-CHOP

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Fondazione Italiana Linfomi - ETS: lead
• Janssen-Cilag S.p.A.: collaborator

Study Sites (39)

Ospedale di Castelfranco Veneto - Oncoematologia IOV

Castelfranco Veneto, Treviso, 31033, Italy

Location

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

Alessandria, 15121, Italy

Location

Università Politecnica delle Marche- Clinica di Ematologia

Ancona, 60121, Italy

Location

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

Avellino, 83100, Italy

Location

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

Aviano, 33081, Italy

Location

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

Bari, 70121, Italy

Location

ASST Spedali Civili di Brescia - Ematologia

Brescia, 25123, Italy

Location

Ospedale Businco - SC Ematologia e CTMO

Cagliari, 09121, Italy

Location

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

Catania, 95123, Italy

Location

Azienda Ospedaliera Universitaria Careggi - Unità funzionale di Ematologia

Florence, 50141, Italy

Location

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

Genova, 16132, Italy

Location

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

Messina, 98158, Italy

Location

Istituto Scientifico San Raffaele - Unità Linfomi - Dipartimento Oncoematologia

Milan, 20132, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano - Ematologia

Milan, 20133, Italy

Location

IEO Istitito Europeo di Oncologia - Divisione Ematoncologia

Milan, 20141, Italy

Location

ASST Grande Ospedale Metropolitano Niguarda - SC Ematologia

Milan, 20162, Italy

Location

Azienda Ospedaliero-Universitaria Policlinico di Modena - Ematologia

Modena, 41123, Italy

Location

Monza - Fondazione IRCCS San Gerardo dei Tintori - Ematologia

Monza, 20900, Italy

Location

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

Naples, 80131, Italy

Location

AOU Maggiore della Carità di Novara - SCDU Ematologia

Novara, 28100, Italy

Location

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

Padua, 35128, Italy

Location

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

Pavia, 27100, Italy

Location

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

Pescara, 65124, Italy

Location

Ospedale Guglielmo da Saliceto - U.O.Ematologia

Piacenza, 29121, Italy

Location

AOU Pisana - U.O. Ematologia

Pisa, 56126, Italy

Location

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

Potenza, 85100, Italy

Location

Ospedale delle Croci - Ematologia

Ravenna, Italy

Location

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

Reggio Emilia, 42123, Italy

Location

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

Rimini, 47923, Italy

Location

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

Roma, Italy

Location

Università Cattolica S. Cuore - Ematologia

Roma, Italy

Location

Casa Sollievo della Sofferenza - UO Ematologia

San Giovanni Rotondo, Italy

Location

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

Terni, Italy

Location

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

Torino, 10126, Italy

Location

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

Torino, 10126, Italy

Location

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

Tricase, 73039, Italy

Location

Azienda Sanitaria Universitaria Integrata Trieste (ASUITS) SC Ematologia

Trieste, Italy

Location

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

Udine, 33100, Italy

Location

Ospedale di Circolo U.O.C Ematologia

Varese, Italy

Location

MeSH Terms

Interventions

ibrutinib

Study Officials

• Maurizio Martelli, Prof.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Ibrutinib in combination to rituximab-CHOP followed by ibrutinib maintenance

Study Record Dates

• First Submitted: October 4, 2018
• First Posted: November 6, 2018
• Study Start: July 2, 2019
• Primary Completion: July 30, 2024
• Study Completion (Estimated): July 1, 2027
• Last Updated: December 24, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (39)