A Study of Ibrutinib With Rituximab in Relapsed or Refractory Mantle Cell Lymphoma
- Conditions
- Lymphoma, Mantle-Cell
- Interventions
- Registration Number
- NCT05564052
- Lead Sponsor
- Janssen Research & Development, LLC
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 36
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Phase 2: Treatment Arm A2 (Rituximab plus Ibrutinib) 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). Phase 2: Treatment Arm A1 (Rituximab plus Ibrutinib) Rituximab 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). Phase 2: Treatment Arm A1 (Rituximab plus Ibrutinib) 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). Phase 2: Treatment Arm A3 (Rituximab plus Ibrutinib) 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). Phase 2: Treatment Arm A2 (Rituximab plus Ibrutinib) Rituximab 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). Phase 2: Treatment Arm A3 (Rituximab plus Ibrutinib) Rituximab 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). Phase 2: Treatment Arm B (Rituximab plus Lenalidomide or Bortezomib) Lenalidomide 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. Phase 2: Treatment Arm B (Rituximab plus Lenalidomide or Bortezomib) Rituximab 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. Phase 2: Treatment Arm B (Rituximab plus Lenalidomide or Bortezomib) 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.
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Arms A1, A2, A3 and B 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) 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs) Leading to Discontinuation of Treatment: Monotherapy Arm 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) 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.
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 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) 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.
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 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) 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.
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs): Arms A1, A2, A3 and B 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) 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.
Number of Participants With Treatment Emergent Serious Adverse Events (TESAEs): Monotherapy Arm 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) 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.
Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Arms A1, A2, A3 and B 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 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.
Number of Participants With Clinical Laboratory Abnormalities: Hematology Parameters: Monotherapy Arm 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 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.
Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Arms A1, A2, A3 and B 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 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.
Number of Participants With Clinical Laboratory Abnormalities: Chemistry Parameters: Monotherapy Arm 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 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.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (66)
Szpital Specjalistyczny im Jedrzeja Sniadeckiego w Nowym Saczu
🇵🇱Nowy Sacz, Poland
Specjalistyczny Szpital im dra Alfreda Sokolowskiego w Walbrzychu
🇵🇱Walbrzych, Poland
Santa Casa de Misericordia de Belo Horizonte
🇧🇷Belo Horizonte, Brazil
Sociedade Beneficente de Senhoras - Hospital Sirio Libanes HSL Unidade Brasilia
🇧🇷Brasilia, Brazil
Ynova Pesquisa Clinica
🇧🇷Florianopolis, Brazil
Liga Norte Riograndense Contra O Cancer
🇧🇷Natal, Brazil
Complexo Hospitalar de Niteroi
🇧🇷Niteroi, Brazil
Irmandade Santa Casa de Misericordia de Porto Alegre
🇧🇷Porto Alegre, Brazil
Hospital Das Clinicas Da Faculdade De Medicina De RPUSP HCRP
🇧🇷Ribeirao Preto, Brazil
Oncoclinicas Rio de Janeiro S A
🇧🇷Rio de Janeiro, Brazil
Instituto de Ensino e Pesquisa Sao Lucas - IEP HEMOMED
🇧🇷Sao Paulo, Brazil
Instituto D Or de Pesquisa e Ensino IDOR
🇧🇷Sao Paulo, Brazil
Casa de Saude Santa Marcelina - Hospital Santa Marcelina
🇧🇷Sao Paulo, Brazil
Fakultni Nemocnice Ostrava
🇨🇿Ostrava, Czechia
Fakultni nemocnice Kralovske Vinohrady
🇨🇿Praha 10, Czechia
General University Hospital in Prague
🇨🇿Praha 2, 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
🇵🇱Brzozow, Poland
Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach
🇵🇱Kielce, Poland
Uniwersytecki Szpital Kliniczny Nr 1 w Lublinie
🇵🇱Lublin, 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
🇵🇱Warszawa, Poland
Auxilio Mutuo Cancer Center
🇵🇷San Juan, Puerto Rico
Spitalul Clinic Coltea
🇷🇴Bucuresti, Romania
Ovidius Clinical Hospital OCH
🇷🇴Ovidiu, Romania
Hosp Reina Sofia
🇪🇸Cordoba, Spain
Hosp. Univ. Infanta Leonor
🇪🇸Madrid, Spain
Clinica Univ. de Navarra
🇪🇸Pamplona, Spain
Hosp. Quiron Madrid Pozuelo
🇪🇸Pozuelo de Alarcon, 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, Taiwan
China Medical University Hospital
🇨🇳Taichung, Taiwan
Chi Mei Medical Center Liu Ying
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
King Chulalongkorn Memorial Hospital
🇹ðŸ‡Bangkok, Thailand
Phramongkutklao Hospital and Medical College
🇹ðŸ‡Bangkok, Thailand
Ramathibodi Hospital
🇹ðŸ‡Bangkok, Thailand
Siriraj Hospital
🇹ðŸ‡Bangkok, Thailand
Maharaj Nakorn Chiang Mai hospital Faculty of Medicine
🇹ðŸ‡ChiangMai, Thailand
Srinagarind Hospital
🇹ðŸ‡Khon Kaen, Thailand
Ankara Bilkent Sehir Hastanesi
🇹🇷Ankara Sehir Hastanesi, Turkey
Ondokuz Mayis University
🇹🇷Atakum, Turkey
Trakya University Medical Faculty
🇹🇷Edirne, Turkey
Medipol Mega University Hospital
🇹🇷Istanbul, Turkey
Istanbul University
🇹🇷Istanbul, Turkey
Ege Universitesi Tip Fakultesi
🇹🇷Izmir, Turkey
Sakarya Egitim Ve Arastırma Hastanesi Korucuk Kampus
🇹🇷Sakarya, Turkey