A Study of Ibrutinib With Rituximab in Relapsed or Refractory Mantle Cell Lymphoma

NCT ID: NCT05564052

Last Updated: 2025-10-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-12-06
• Study Completion Date: 2024-09-26

Brief Summary

The purpose of this study is to provide continued access to treatment for participants who continue to benefit from treatment.

Detailed Description

Mantle cell lymphoma (MCL) is an uncommon and incurable clinicopathologic subtype of B-cell non-Hodgkin Lymphoma (NHL). Ibrutinib is a first-in-class potent, orally administered, covalently-binding small molecule inhibitor of Bruton's tyrosine kinase (BTKi) for the treatment of B-cell malignancies and chronic graft-versus-host disease. The primary hypothesis of the study is to provide continued access to treatment for participants who continue to benefit from treatment. The study will include a screening phase (up to 30 days prior to randomization), a treatment phase (from randomization until study treatment discontinuation). safety assessments include adverse events (AEs), serious adverse events (SAEs), clinical laboratory tests, vital signs, electrocardiogram (ECG), physical examination. The Phase 2 exploratory objectives and endpoints of characterization of pharmacokinetic and pharmacodynamic of ibrutinib may continue to be evaluated using blood samples already collected. The total duration of the study will be up to 2 years 1 month.

Conditions

Lymphoma, Mantle-Cell

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 2: Treatment Arm A1 (Rituximab plus Ibrutinib)

Participants will receive rituximab 375 milligrams per meter square (mg/m\^2) intravenously (IV) on Day 1 of Cycles 1 to 6 with ibrutinib 560 milligrams (mg) orally, once daily starting on Day 1 of Cycle 1 until disease progression or unacceptable toxicity (each cycle length is 28 days).

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

Ibrutinib capsules will be administered orally.

Rituximab

Intervention Type: DRUG

Rituximab will be administered IV.

Phase 2: Treatment Arm A2 (Rituximab plus Ibrutinib)

Participants will receive rituximab 375 mg/m\^2 IV on Day 1 of Cycles 1 to 6 with ibrutinib 420 mg orally, once daily starting on Day 1 of Cycle 1 until disease progression or unacceptable toxicity (each cycle length is 28 days).

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

Ibrutinib capsules will be administered orally.

Rituximab

Intervention Type: DRUG

Rituximab will be administered IV.

Phase 2: Treatment Arm A3 (Rituximab plus Ibrutinib)

Participants will receive rituximab 375 mg/m\^2 IV on Day 1 of Cycles 1 to 6 with ibrutinib 140 mg orally, twice daily starting on Day 1 of Cycle 1 until disease progression or unacceptable toxicity (each cycle length is 28 days).

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

Ibrutinib capsules will be administered orally.

Rituximab

Intervention Type: DRUG

Rituximab will be administered IV.

Phase 2: Treatment Arm B (Rituximab plus Lenalidomide or Bortezomib)

Participants will receive rituximab 375 mg/m\^2 IV on Day 1 of Cycles 1 to 6 (each cycle length is 21 or 28 days) with physician's choice of either lenalidomide 20 mg orally, once daily from Day 1 through Day 21 of 28-day cycle or bortezomib 1.3 mg/m\^2 IV or subcutaneously (SC) on Days 1, 4, 8 and 11 of a 21-day cycle until disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

Lenalidomide

Intervention Type: DRUG

Lenalidomide capsules will be administered orally.

Rituximab

Intervention Type: DRUG

Rituximab will be administered IV.

Bortezomib

Intervention Type: DRUG

Bortezomib will be administered either intravenously or subcutaneously.

Interventions

Ibrutinib

Ibrutinib capsules will be administered orally.

Intervention Type: DRUG

Lenalidomide

Lenalidomide capsules will be administered orally.

Intervention Type: DRUG

Rituximab

Rituximab will be administered IV.

Intervention Type: DRUG

Bortezomib

Bortezomib will be administered either intravenously or subcutaneously.

Intervention Type: DRUG

Other Intervention Names

JNJ-54179060, IMBRUVICA, PCI-32765

Eligibility Criteria

Inclusion Criteria

• At least 1 prior treatment regimen for mantle cell lymphoma (MCL) excluding inhibitor of Bruton's tyrosine kinase (BTKi)
• Documented disease progression or relapse following the last anti-MCL treatment
• At least 1 measurable site of disease on cross-sectional imaging that is greater than or equal to (>=) 2.0 centimeters (cm) in the longest diameter and measurable in 2 perpendicular dimensions per computed tomography (CT)
• Eastern Cooperative Oncology Group (ECOG) performance status score 0 or 1

Exclusion Criteria

• Prior therapy with ibrutinib or other BTK inhibitor
• Prior treatment with both lenalidomide and bortezomib. Prior treatment with only 1 of these therapies is allowed
• Major surgery within 4 weeks of randomization
• Concurrent enrollment in another therapeutic investigational study
• Known central nervous system lymphoma
• History of stroke or intracranial hemorrhage within 6 months prior to randomization

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pharmacyclics LLC.

INDUSTRY

Sponsor Role: collaborator

Janssen Research & Development, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Janssen Research & Development, LLC Clinical Trial

Role: STUDY_DIRECTOR

Janssen Research & Development, LLC

Locations

Santa Casa de Misericordia de Belo Horizonte

Belo Horizonte, , Brazil

Sociedade Beneficente de Senhoras - Hospital Sirio Libanes HSL Unidade Brasilia

Brasília, , Brazil

Ynova Pesquisa Clinica

Florianópolis, , Brazil

Liga Norte Riograndense Contra O Cancer

Natal, , Brazil

Complexo Hospitalar de Niteroi

Niterói, , Brazil

Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, , Brazil

Hospital Das Clinicas Da Faculdade De Medicina De RPUSP HCRP

Ribeirão Preto, , Brazil

Oncoclinicas Rio de Janeiro S A

Rio de Janeiro, , Brazil

Instituto de Ensino e Pesquisa Sao Lucas - IEP HEMOMED

São Paulo, , Brazil

Instituto D Or de Pesquisa e Ensino IDOR

São Paulo, , Brazil

Casa de Saude Santa Marcelina - Hospital Santa Marcelina

São Paulo, , Brazil

Fakultni Nemocnice Ostrava

Ostrava, , Czechia

Fakultni nemocnice Kralovske Vinohrady

Prague, , Czechia

General University Hospital in Prague

Prague, , Czechia

Attikon University General Hospital of Attica

Athens, , Greece

University Hospital of Ioannina

Ioannina, , Greece

G.Papanikolaou

Thessaloniki, , Greece

Healthcare Global (HCG) Hospital

Bangalore, , India

American Oncology Institute Cancer Treatment Hospital Hyderabad

Hyderabad, , India

Bhagwan Mahaveer Cancer Hospital & Research Centre

Jaipur, , India

HCG cancer center

Jaipur, , India

Tata Medical Center

Kolkata, , India

AMRI Hospital, Mukundapur

Mukundapur, , India

Deenanath Mangeshkar Hospital and Research Centre

Pune, , India

Synergy Superspeciality Hospital

Rajkot, , India

Hospital Ampang

Ampang, , Malaysia

Hospital Sultanah Aminah

Johor Bharu, , Malaysia

Hospital Queen Elizabeth

Kota Kinabalu, , Malaysia

University Malaya Medical Centre

Kuala Lumpur, , Malaysia

Subang Jaya Medical Centre

Subang Jaya, , Malaysia

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza

Brzozów, , Poland

Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach

Kielce, , Poland

Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie

Lublin, , Poland

Szpital Specjalistyczny im Jedrzeja Sniadeckiego w Nowym Saczu

Nowy Sącz, , Poland

SPZOZ Ministerstwa Spraw Wewnetrznych z Warminsko Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, , Poland

Centrum Medyczne Pratia Poznan

Skorzewo, , Poland

Samodzielny Publiczny Szpital Kliniczny Nr 1 PUM im prof Tadeusza Sokolowskiego w Szczecinie

Szczecin, , Poland

Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy

Warsaw, , Poland

Specjalistyczny Szpital im dra Alfreda Sokolowskiego w Walbrzychu

Wałbrzych, , Poland

Auxilio Mutuo Cancer Center

San Juan, , Puerto Rico

Spitalul Clinic Coltea

Bucharest, , Romania

Ovidius Clinical Hospital OCH

Ovidiu, , Romania

Hosp Reina Sofia

Córdoba, , Spain

Hosp. Univ. Infanta Leonor

Madrid, , Spain

Clinica Univ. de Navarra

Pamplona, , Spain

Hosp. Quiron Madrid Pozuelo

Pozuelo de Alarcón, , Spain

Hosp Clinico Univ de Salamanca

Salamanca, , Spain

Falu Lasarett Medicinkliniken Falun

Falun, , Sweden

Sunderby Sjukhus

Luleå, , Sweden

Kaohsiung Medical University Chung Ho Memorial Hospital

Kaohsiung City, , Taiwan

China Medical University Hospital

Taichung, , Taiwan

Chi Mei Medical Center Liu Ying

Tainan City, , Taiwan

National Taiwan University Hospital

Taipei, , Taiwan

King Chulalongkorn Memorial Hospital

Bangkok, , Thailand

Phramongkutklao Hospital and Medical College

Bangkok, , Thailand

Ramathibodi Hospital

Bangkok, , Thailand

Siriraj Hospital

Bangkok, , Thailand

Maharaj Nakorn Chiang Mai hospital Faculty of Medicine

Chiang Mai, , Thailand

Srinagarind Hospital

Khon Kaen, , Thailand

Ankara Bilkent Sehir Hastanesi

Ankara Sehir Hastanesi, , Turkey (Türkiye)

Ondokuz Mayis University

Atakum, , Turkey (Türkiye)

Trakya University Medical Faculty

Edirne, , Turkey (Türkiye)

Medipol Mega University Hospital

Istanbul, , Turkey (Türkiye)

Istanbul University

Istanbul, , Turkey (Türkiye)

Ege Universitesi Tip Fakultesi

Izmir, , Turkey (Türkiye)

Sakarya Egitim Ve Arastırma Hastanesi Korucuk Kampus

Sakarya, , Turkey (Türkiye)

Countries

Brazil; Czechia; Greece; India; Malaysia; Poland; Puerto Rico; Romania; Spain; Sweden; Taiwan; Thailand; Turkey (Türkiye)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

54179060MCL3004

Identifier Type: OTHER

Identifier Source: secondary_id

2022-000364-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2023-503618-64-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

CR109252

Identifier Type: -

Identifier Source: org_study_id