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

A Randomized, Controlled, Open-label, Multicenter, Inferentially Seamless Phase 2/3 Study of Ibrutinib in Combination With Rituximab Versus Physician's Choice of Lenalidomide Plus Rituximab or Bortezomib Plus Rituximab in Participants With Relapsed or Refractory Mantle Cell Lymphoma

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

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma, Mantle-Cell
• Intervention / Treatment: Drug: Ibrutinib; Drug: Rituximab; Drug: Lenalidomide; Drug: Bortezomib

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.

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• Brazil
  • Belo Horizonte, Brazil, 30150-221
    • Santa Casa de Misericordia de Belo Horizonte
  • Brasilia, Brazil, 70200-730
    • Sociedade Beneficente de Senhoras - Hospital Sirio Libanes HSL Unidade Brasilia
  • Florianopolis, Brazil, 88020-210
    • Ynova Pesquisa Clinica
  • Natal, Brazil, 59062-000
    • Liga Norte Riograndense Contra O Cancer
  • Niteroi, Brazil, 24020-096
    • Complexo Hospitalar de Niteroi
  • Porto Alegre, Brazil, 90050-170
    • Irmandade Santa Casa de Misericordia de Porto Alegre
  • Ribeirao Preto, Brazil, 14051-140
    • Hospital Das Clinicas Da Faculdade De Medicina De RPUSP HCRP
  • Rio de Janeiro, Brazil, 22 250 905
    • Oncoclinicas Rio de Janeiro S A
  • Sao Paulo, Brazil, 08270-120
    • Casa de Saude Santa Marcelina - Hospital Santa Marcelina
  • Sao Paulo, Brazil, 01236-030
    • Instituto de Ensino e Pesquisa Sao Lucas - IEP HEMOMED
  • Sao Paulo, Brazil, 04501-000
    • Instituto D Or de Pesquisa e Ensino (IDOR)
• Czechia
  • Ostrava, Czechia, 708 52
    • Fakultni nemocnice Ostrava
  • Praha 10, Czechia, 100 34
    • Fakultni nemocnice Kralovske Vinohrady
  • Praha 2, Czechia, 128 08
    • General University Hospital in Prague
• Greece
  • Athens, Greece, 12462
    • Attikon University General Hospital of Attica
  • Ioannina, Greece, 45110
    • University Hospital of Ioannina
  • Thessaloniki, Greece, 57010
    • G.Papanikolaou
• India
  • Bangalore, India, 560027
    • Healthcare Global (HCG) Hospital
  • Hyderabad, India, 500019
    • American Oncology Institute Cancer Treatment Hospital Hyderabad
  • Jaipur, India, 302017
    • Bhagwan Mahaveer Cancer Hospital & Research Centre
  • Jaipur, India, 302020
    • HCG cancer center
  • Kolkata, India, 700156
    • Tata Medical Center
  • Mukundapur, India, 700099
    • AMRI Hospital, Mukundapur
  • Pune, India, 411004
    • Deenanath Mangeshkar Hospital and Research Centre
  • Rajkot, India, 360005
    • Synergy Superspeciality Hospital
• Malaysia
  • Ampang, Malaysia, 68000
    • Hospital Ampang
  • Johor Bharu, Malaysia, 80100
    • Hospital Sultanah Aminah
  • Kota Kinabalu, Malaysia, 88586
    • Hospital Queen Elizabeth
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre
  • Subang Jaya, Malaysia, 47500
    • Subang Jaya Medical Centre
• Poland
  • Brzozów, Poland, 36-200
    • Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im Ks B Markiewicza
  • Kielce, Poland, 25-734
    • Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach
  • Lublin, Poland, 20-081
    • Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie
  • Nowy Sącz, Poland, 33-300
    • Szpital Specjalistyczny im Jędrzeja Śniadeckiego w Nowym Saczu
  • Olsztyn, Poland, 10-228
    • SPZOZ Ministerstwa Spraw Wewnetrznych z Warminsko Mazurskim Centrum Onkologii w Olsztynie
  • Skorzewo, Poland, 60-185
    • Centrum Medyczne Pratia Poznan
  • Szczecin, Poland, 71252
    • Samodzielny Publiczny Szpital Kliniczny Nr 1 PUM im prof Tadeusza Sokolowskiego w Szczecinie
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
  • Wałbrzych, Poland, 58-309
    • Specjalistyczny Szpital im. dra Alfreda Sokołowskiego w Wałbrzychu
• Puerto Rico
  • San Juan, Puerto Rico, 00918
    • Auxilio Mutuo Cancer Center
• Romania
  • Bucuresti, Romania, 030167
    • Spitalul Clinic Coltea
  • Ovidiu, Romania, 905900
    • Ovidius Clinical Hospital OCH
• Spain
  • Cordoba, Spain, 14004
    • Hosp. Reina Sofia
  • Madrid, Spain, 28031
    • Hosp. Univ. Infanta Leonor
  • Pamplona, Spain, 31008
    • Clinica Univ. de Navarra
  • Pozuelo de Alarcon, Spain, 28223
    • Hosp. Quiron Madrid Pozuelo
  • Salamanca, Spain, 37007
    • Hosp. Clinico Univ. de Salamanca
• Sweden
  • Falun, Sweden, 791 82
    • Falu Lasarett Medicinkliniken Falun
  • Luleå, Sweden, 97180
    • Sunderby Sjukhus
• Taiwan
  • Kaohsiung, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Taichung, Taiwan, 404327
    • China Medical University Hospital
  • Tainan, Taiwan, 736
    • Chi Mei Medical Center - Liu Ying
  • Taipei, Taiwan, 100
    • National Taiwan University Hospital
• Thailand
  • Bangkok, Thailand, 10330
    • King Chulalongkorn Memorial Hospital
  • Bangkok, Thailand, 10700
    • Siriraj Hospital
  • Bangkok, Thailand, 10400
    • Ramathibodi Hospital
  • Bangkok, Thailand, 10400
    • Phramongkutklao Hospital and Medical College
  • ChiangMai, Thailand, 50200
    • Maharaj Nakorn Chiang Mai hospital - Faculty of Medicine
  • Khon Kaen, Thailand, 40002
    • Srinagarind Hospital
• Turkey
  • Ankara Sehir Hastanesi, Turkey, 06800
    • Ankara Bilkent Sehir Hastanesi
  • Atakum, Turkey, 55270
    • Ondokuz Mayis Universitesi Tip Fakultesi
  • Edirne, Turkey, 22030
    • Trakya University Medical Faculty
  • Istanbul, Turkey, 34214
    • Medipol Mega University Hospital
  • Istanbul, Turkey, 34390
    • Istanbul University
  • Izmir, Turkey, 35100
    • Ege Universitesi Tip Fakultesi
  • Sakarya, Turkey, 54290
    • Sakarya Egitim Ve Arastırma Hastanesi Korucuk Kampus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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).	Drug: Ibrutinib; Ibrutinib capsules will be administered orally.; Other Names: JNJ-54179060, IMBRUVICA, PCI-32765; Drug: Rituximab; Rituximab will be administered IV.
Experimental: 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).	Drug: Ibrutinib; Ibrutinib capsules will be administered orally.; Other Names: JNJ-54179060, IMBRUVICA, PCI-32765; Drug: Rituximab; Rituximab will be administered IV.
Experimental: 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).	Drug: Ibrutinib; Ibrutinib capsules will be administered orally.; Other Names: JNJ-54179060, IMBRUVICA, PCI-32765; Drug: Rituximab; Rituximab will be administered IV.
Experimental: 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.	Drug: Rituximab; Rituximab will be administered IV.; Drug: Lenalidomide; Lenalidomide capsules will be administered orally.; Drug: Bortezomib; Bortezomib will be administered either intravenously or subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Adverse Events (AEs) that Resulted in Discontinuation of Treatment, Severe AE, or Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. SAE defined as results in death, is life-threatening (the participant was at risk of death at the time of the event. It does not refer to an event that hypothetically might have caused death if it were more severe), requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is a suspected transmission of any infectious agent via a medicinal product, and is Medically Important.	Up to 6 months
Number of Participants with Abnormalities in Clinical Laboratory Parameters	Number of participants with abnormalities in clinical laboratory parameters (hematology and serum chemistry) will be reported.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 3: Overall Response Rate (ORR)	ORR is defined as the percentage of participants who achieve CR or partial response (PR) as the best overall response on or prior to initiation of subsequent antineoplastic therapy according to Lugano 2014 criteria based on IRC assessment.	Up to 60 months
Phase 3: Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of the participant's death.	Up to 129 months
Phase 3: Complete Response Rate (CRR)	CRR is defined as the percentage of participants who achieve CR on or prior to the initiation of subsequent anticancer therapy according to Lugano 2014 criteria based on IRC assessment.	Up to 60 months
Phase 3: Time-to-next Treatment (TTNT)	TTNT is defined as interval from the date of randomization to the start date of any anti-mantle cell lymphoma (MCL) treatment subsequent to the study treatment.	Up to 60 months
Phase 3: Number of Participants with AEs	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the intervention under study.	Up to 60 months
Phase 3: Number of Participants with AEs by Severity	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the intervention under study. Severity will be graded according to the NCI-CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event.	Up to 60 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Collaborators: Pharmacyclics LLC.
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2022
• Primary Completion (Actual): December 6, 2023
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: September 30, 2022
• First Submitted That Met QC Criteria: September 30, 2022
• First Posted (Actual): October 3, 2022

Study Record Updates

• Last Update Posted (Estimated): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Lenalidomide; Rituximab; Bortezomib; Ibrutinib
• Other Study ID Numbers: CR109252; 2022-000364-21 (EudraCT Number); 54179060MCL3004 (Other Identifier: Janssen Research & Development, LLC); 2023-503618-64-00 (Registry Identifier: EUCT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No