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

NCT05564052 | Completed Phase 2 Results FDA Drug

• 4 other identifiers: CR10925254179060MCL30042022-000364-212023-503618-64-00
• Study Type: interventional
• Target: 36
• Locations: 13 countries
• Sites: 66

Brief Summary

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

Conditions

Lymphoma, Mantle-Cell

Outcome Measures

Primary Outcomes (10)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Arms A1, A2, A3 and B

  An adverse event (AE) was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs was defined as any new or worsening AE occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. All TEAEs including serious and non-serious events were reported in this outcome measure.

  From start of treatment (Day 1) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 12 months)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Monotherapy Arm

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs was defined as any new or worsening AE occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. All TEAEs included serious and non-serious events were reported in this outcome measure.

  From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 6 months)

• Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0: Arms A1, A2, A3 and B

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs was defined as any new or worsening AE occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. TEAEs were graded according to NCI-CTCAE v5.0 as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe or medically significant but not immediately life-threatening; Grade 4- Life-threatening consequences and Grade 5- Death related to AE. Number of participants with grade 3 or higher TEAEs (including serious and non-serious events) were reported in this outcome measure.

  From start of treatment (Day 1) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 12 months)

• Number of Participants With Grade 3 or Higher TEAEs Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version (v) 5.0: Monotherapy Arm

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs was defined as any new or worsening AE occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first. TEAEs were graded according to NCI-CTCAE v5.0 as Grade 1- Mild; Grade 2- Moderate; Grade 3- Severe or medically significant but not immediately life-threatening; Grade 4- Life-threatening consequences and Grade 5- Death related to AE. Number of participants with grade 3 or higher TEAEs (including serious and non-serious events) were reported in this outcome measure.

  From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 6 months)

• Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs): Arms A1, A2, A3 and B

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A serious AE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, or was medically important. TESAEs was defined as SAEs occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first.

  From start of treatment (Day 1) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 12 months)

• Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs): Monotherapy Arm

  An AE was any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. A serious AE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a suspected transmission of any infectious agent via a medicinal product, or was medically important. TESAEs was defined as SAEs occurring at or after first dose of study treatment up to 30 days after last dose or prior to start of subsequent anticancer therapy, whichever occurred first.

  From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug or start of subsequent anticancer therapy, whichever occurred first (up to 6 months)

• Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B

  Number of participants with clinical abnormalities in hematology laboratory parameters were reported. Hematology parameters included: Activated partial thromboplastin time (aPTT), hemoglobin, neutrophil count, white blood cell (WBC) count, lymphocyte count, platelet count and prothrombin international normalized ratio (INR). Abnormality criteria was assessed as per NCI CTCAE v5.0 grading, where Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Grade 0 was assigned when the laboratory value was not assigned a Grade 1 or higher. Only those categories in which at least 1 participant had data were reported.

  From start of treatment (Day 1) up to 30 days after last dose of study drug (up to 12 months)

• Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm

  Number of participants with clinical abnormalities in hematology laboratory parameters were reported. Hematology parameters included: Activated partial thromboplastin time (aPTT), hemoglobin, neutrophil count, white blood cell (WBC) count, lymphocyte count, platelet count and prothrombin international normalized ratio (INR). Abnormality criteria was assessed as per NCI CTCAE v5.0 grading, where Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Grade 0 was assigned when the laboratory value was not assigned a Grade 1 or higher. Only those categories in which at least 1 participant had data were reported.

  From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug (up to 6 months)

• Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B

  Number of participants with clinical abnormalities in chemistry laboratory parameters were reported. Chemistry parameters included: sodium, aspartate aminotransferase (AST), potassium, alanine aminotransferase (ALT), creatinine, total bilirubin (BL), alkaline phosphatase, albumin, and calcium. Abnormality criteria was assessed as per NCI CTCAE v5.0 grading, where Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Grade 0 was assigned when the laboratory value was not assigned a Grade 1 or higher. Only those categories in which at least 1 participant had data were reported.

  From start of treatment (Day 1) up to 30 days after last dose of study drug (up to 12 months)

• Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm

  Number of participants with clinical abnormalities in chemistry laboratory parameters were reported. Chemistry parameters included: sodium, aspartate aminotransferase (AST), potassium, alanine aminotransferase (ALT), creatinine, total bilirubin, alkaline phosphatase, albumin, and calcium. Abnormality criteria was assessed as per NCI CTCAE v5.0 grading, where Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening. Grade 0 was assigned when the laboratory value was not assigned a Grade 1 or higher. Only those categories in which at least 1 participant had data were reported.

  From start of monotherapy (post protocol amendment 1, dated 08 June 2023) up to 30 days after last dose of study drug (up to 6 months)

Study Arms (4)

Phase 2: Treatment Arm A1 (Rituximab plus Ibrutinib)

EXPERIMENTAL

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).

Drug: Ibrutinib; Drug: Rituximab

Phase 2: Treatment Arm A2 (Rituximab plus Ibrutinib)

EXPERIMENTAL

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).

Drug: Ibrutinib; Drug: Rituximab

Phase 2: Treatment Arm A3 (Rituximab plus Ibrutinib)

EXPERIMENTAL

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).

Drug: Ibrutinib; Drug: Rituximab

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

EXPERIMENTAL

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.

Drug: Lenalidomide; Drug: Rituximab; Drug: Bortezomib

Interventions

Ibrutinib DRUG

Ibrutinib capsules will be administered orally.

Also known as: JNJ-54179060, IMBRUVICA, PCI-32765

Phase 2: Treatment Arm A1 (Rituximab plus Ibrutinib); Phase 2: Treatment Arm A2 (Rituximab plus Ibrutinib); Phase 2: Treatment Arm A3 (Rituximab plus Ibrutinib)

Lenalidomide DRUG

Lenalidomide capsules will be administered orally.

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

Rituximab DRUG

Rituximab will be administered IV.

Phase 2: Treatment Arm A1 (Rituximab plus Ibrutinib); Phase 2: Treatment Arm A2 (Rituximab plus Ibrutinib); Phase 2: Treatment Arm A3 (Rituximab plus Ibrutinib); Phase 2: Treatment Arm B (Rituximab plus Lenalidomide or Bortezomib)

Bortezomib DRUG

Bortezomib will be administered either intravenously or subcutaneously.

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead
• Pharmacyclics LLC.: collaborator

Study Sites (66)

Santa Casa de Misericordia de Belo Horizonte

Belo Horizonte, 30150-221, Brazil

Location

Sociedade Beneficente de Senhoras - Hospital Sirio Libanes HSL Unidade Brasilia

Brasília, 70200-730, Brazil

Location

Ynova Pesquisa Clinica

Florianópolis, 88020-210, Brazil

Location

Liga Norte Riograndense Contra O Cancer

Natal, 59062-000, Brazil

Location

Complexo Hospitalar de Niteroi

Niterói, 24020-096, Brazil

Location

Irmandade Santa Casa de Misericordia de Porto Alegre

Porto Alegre, 90050 170, Brazil

Location

Hospital Das Clinicas Da Faculdade De Medicina De RPUSP HCRP

Ribeirão Preto, 14051-140, Brazil

Location

Oncoclinicas Rio de Janeiro S A

Rio de Janeiro, 22 250 905, Brazil

Location

Instituto de Ensino e Pesquisa Sao Lucas - IEP HEMOMED

São Paulo, 01236-030, Brazil

Location

Instituto D Or de Pesquisa e Ensino IDOR

São Paulo, 04501-000, Brazil

Location

Casa de Saude Santa Marcelina - Hospital Santa Marcelina

São Paulo, 08270-120, Brazil

Location

Fakultni Nemocnice Ostrava

Ostrava, 708 52, Czechia

Location

Fakultni nemocnice Kralovske Vinohrady

Prague, 100 34, Czechia

Location

General University Hospital in Prague

Prague, 128 08, Czechia

Location

Attikon University General Hospital of Attica

Athens, 12462, Greece

Location

University Hospital of Ioannina

Ioannina, 45110, Greece

Location

G.Papanikolaou

Thessaloniki, 57010, Greece

Location

Healthcare Global (HCG) Hospital

Bangalore, 560027, India

Location

American Oncology Institute Cancer Treatment Hospital Hyderabad

Hyderabad, 500019, India

Location

Bhagwan Mahaveer Cancer Hospital & Research Centre

Jaipur, 302017, India

Location

HCG cancer center

Jaipur, 302020, India

Location

Tata Medical Center

Kolkata, 700156, India

Location

AMRI Hospital, Mukundapur

Mukundapur, 700099, India

Location

Deenanath Mangeshkar Hospital and Research Centre

Pune, 411004, India

Location

Synergy Superspeciality Hospital

Rajkot, 360005, India

Location

Hospital Ampang

Ampang, 68000, Malaysia

Location

Hospital Sultanah Aminah

Johor Bharu, 80100, Malaysia

Location

Hospital Queen Elizabeth

Kota Kinabalu, 88586, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, 59100, Malaysia

Location

Subang Jaya Medical Centre

Subang Jaya, 47500, Malaysia

Location

Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza

Brzozów, 36 200, Poland

Location

Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach

Kielce, 25 734, Poland

Location

Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie

Lublin, 20-081, Poland

Location

Szpital Specjalistyczny im Jedrzeja Sniadeckiego w Nowym Saczu

Nowy Sącz, 33 300, Poland

Location

SPZOZ Ministerstwa Spraw Wewnetrznych z Warminsko Mazurskim Centrum Onkologii w Olsztynie

Olsztyn, 10-228, Poland

Location

Centrum Medyczne Pratia Poznan

Skorzewo, 60 185, Poland

Location

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

Szczecin, 71252, Poland

Location

Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy

Warsaw, 02-781, Poland

Location

Specjalistyczny Szpital im dra Alfreda Sokolowskiego w Walbrzychu

Wałbrzych, 58 309, Poland

Location

Auxilio Mutuo Cancer Center

San Juan, 00918, Puerto Rico

Location

Spitalul Clinic Coltea

Bucharest, 030167, Romania

Location

Ovidius Clinical Hospital OCH

Ovidiu, 905900, Romania

Location

Hosp Reina Sofia

Córdoba, 14004, Spain

Location

Hosp. Univ. Infanta Leonor

Madrid, 28031, Spain

Location

Clinica Univ. de Navarra

Pamplona, 31008, Spain

Location

Hosp. Quiron Madrid Pozuelo

Pozuelo de Alarcón, 28223, Spain

Location

Hosp Clinico Univ de Salamanca

Salamanca, 37007, Spain

Location

Falu Lasarett Medicinkliniken Falun

Falun, 791 82, Sweden

Location

Sunderby Sjukhus

Luleå, 97180, Sweden

Location

Kaohsiung Medical University Chung Ho Memorial Hospital

Kaohsiung City, 80756, Taiwan

Location

China Medical University Hospital

Taichung, 404327, Taiwan

Location

Chi Mei Medical Center Liu Ying

Tainan, 736, Taiwan

Location

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

King Chulalongkorn Memorial Hospital

Bangkok, 10330, Thailand

Location

Phramongkutklao Hospital and Medical College

Bangkok, 10400, Thailand

Location

Ramathibodi Hospital

Bangkok, 10400, Thailand

Location

Siriraj Hospital

Bangkok, 10700, Thailand

Location

Maharaj Nakorn Chiang Mai hospital Faculty of Medicine

Chiang Mai, 50200, Thailand

Location

Srinagarind Hospital

Khon Kaen, 40002, Thailand

Location

Ankara Bilkent Sehir Hastanesi

Ankara Sehir Hastanesi, 06800, Turkey (Türkiye)

Location

Ondokuz Mayis University

Atakum, 55270, Turkey (Türkiye)

Location

Trakya University Medical Faculty

Edirne, 22030, Turkey (Türkiye)

Location

Medipol Mega University Hospital

Istanbul, 34214, Turkey (Türkiye)

Location

Istanbul University

Istanbul, 34390, Turkey (Türkiye)

Location

Ege Universitesi Tip Fakultesi

Izmir, 35100, Turkey (Türkiye)

Location

Sakarya Egitim Ve Arastırma Hastanesi Korucuk Kampus

Sakarya, 54290, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

ibrutinib; Lenalidomide; Rituximab; Bortezomib

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Boronic Acids; Acids, Noncarboxylic; Acids; Inorganic Chemicals; Boron Compounds; Pyrazines

Results Point of Contact

• Title: Sr. Director Clinical Sciences Onc
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 30, 2022
• First Posted: October 3, 2022
• Study Start: December 6, 2022
• Primary Completion: December 6, 2023
• Study Completion: September 26, 2024
• Last Updated: October 7, 2025
• Results First Posted: January 13, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

TU (7); IN (8); MY (5); PL (9); BR (11); RO (2); ES (5); TH (6); GR (3); CZ (3); PR (1); TW (4); SE (2)