Study of Ibrutinib (a Bruton's Tyrosine Kinase Inhibitor), Versus Temsirolimus in Patients With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy

NCT ID: NCT01646021

Last Updated: 2018-01-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-12-10
• Study Completion Date: 2016-12-15

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of ibrutinib versus temsirolimus in patients with relapsed or refractory mantle cell lymphoma who received at least 1 prior chemotherapy regimen.

Detailed Description

This is a randomized (individuals assigned to study treatment by chance), open-label (identity of assigned study drug will be known), study to evaluate the efficacy and safety of ibrutinib when compared with temsirolimus in patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 1 prior rituximab-containing chemotherapy regimen. Approximately 280 eligible patients will be randomly assigned in a 1:1 ratio and stratified (grouped) by the number of prior lines of therapy (1 or 2 versus >=3) and simplified MCL International Prognostic Index criteria to receive either ibrutinib by mouth (Treatment Arm A) or temsirolimus intravenous infusion (Treatment Arm B). The study will consist of screening, treatment, and posttreatment phases. Data will be collected on disease response to the treatment, progression-free survival, overall survival, subsequent anti-MCL therapies, patient reported outcomes, and medical resource utilization. Tumor samples, blood collected at multiple time points, and a bone marrow aspirate will be evaluated to identify markers predictive of response or resistance to ibrutinib. Serial pharmacokinetic (study of what the body does to a drug) samples will be collected as detailed in the protocol. Safety will be monitored throughout the study. Disease evaluations will be performed every 9 weeks for up to 15 months from the start of study drug, and every 24 weeks thereafter, until disease progression, death, or the clinical cutoff, whichever comes first. Patients who receive treatment with temsirolimus and have disease progression (confirmed by an Independent Review Committee) may be eligible to crossover and receive treatment with ibrutinib 560 mg orally, daily, on a 21-day cycle until disease progression, unacceptable toxicity, or study end. Data will be analyzed up to 3 years after the last patient is enrolled for the final follow-up.

Conditions

Mantle Cell Lymphoma

Study Design

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

Study Groups

Ibrutinib

Group Type: EXPERIMENTAL

Ibrutinib

Intervention Type: DRUG

560 mg once daily continuous (without interruption) by mouth for 21-day cycles

Temsirolimus

Group Type: EXPERIMENTAL

Temsirolimus

Intervention Type: DRUG

175 mg once daily intravenous infusion on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each 21-day cycle

Interventions

Ibrutinib

560 mg once daily continuous (without interruption) by mouth for 21-day cycles

Intervention Type: DRUG

Temsirolimus

175 mg once daily intravenous infusion on Days 1, 8, 15 of the first cycle followed by 75 mg on Days 1, 8, 15 of each 21-day cycle

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Confirmed diagnosis of mantle cell lymphoma (MCL)
• Received at least 1 prior rituximab-containing chemotherapy regimen (separate lines of therapy are defined as single or combination therapies that are either separated by disease progression or by a > 6 month treatment-free interval)
• Documented relapse or disease progression following the last anti-MCL treatment
• At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
• Eastern Cooperative Oncology Group performance status grade 0 or 1
• Protocol-defined hematology and biochemistry laboratory values

Exclusion Criteria

• Prior nitrosoureas within 6 weeks, chemotherapy within 3 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, or major surgery within 4 weeks of randomization
• Prior treatment with temsirolimus, other mTOR inhibitors, ibrutinib, or other Bruton's tyrosine kinase (BTK) inhibitors
• Known central nervous system lymphoma
• Received an allogeneic or autologous hematopoietic stem cell transplant <=6 months from the date of randomization and on immunosuppressive therapy or have evidence of active graft versus host disease
• Diagnosed or treated for malignancy other than MCL, except: malignancy treated with curative intent and with no known active disease present for >=3 years before randomization, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, adequately treated cervical carcinoma in situ without evidence of disease
• History of stroke or intracranial hemorrhage within 6 months prior to randomization
• Requires anticoagulation with warfarin or equivalent vitamin K antagonist
• Requires treatment with strong CYP3A inhibitor
• Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
• Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or active hepatitis B virus (HBV) infection or any uncontrolled active systemic infection requiring intravenous antibiotics
• Woman who is pregnant or breast-feeding
• Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk

• 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

Antwerp, , Belgium

Bruges, , Belgium

Brussels, , Belgium

Edegem, , Belgium

Ghent, , Belgium

Leuven, , Belgium

Wilrijk, , Belgium

Goiânia, , Brazil

Porto Alegre, , Brazil

Ribeirão Preto, , Brazil

Rio de Janeiro, , Brazil

São Paulo, , Brazil

Edmonton, Alberta, Canada

Ottawa, Ontario, Canada

Montreal, Quebec, Canada

Temuco, , Chile

Bogotá, , Colombia

Medellín, , Colombia

Brno, , Czechia

Prague, , Czechia

Mulhouse, , France

Paris, , France

Pessac, , France

Villejuif, , France

Berlin, , Germany

Cologne, , Germany

Essen, , Germany

Heidelberg, , Germany

Homburg, , Germany

Kiel, , Germany

Mainz, , Germany

München, , Germany

Ulm, , Germany

Budapest, , Hungary

Debrecen, , Hungary

Pécs, , Hungary

Szeged, , Hungary

Dublin, , Ireland

Monterrey, , Mexico

Oaxaca City, , Mexico

Querétaro, , Mexico

Amsterdam, , Netherlands

Rotterdam, , Netherlands

Brzozów, , Poland

Chorzów, , Poland

Gdansk, , Poland

Krakow, , Poland

Opole, , Poland

Słupsk, , Poland

Wroclaw, , Poland

Coimbra, , Portugal

Lisbon, , Portugal

Porto, , Portugal

Chelyabinsk, , Russia

Krasnodar, , Russia

Moscow, , Russia

Nizhny Novgorod, , Russia

Obninsk, , Russia

Rostov-on-Don, , Russia

Saint Petersburg, , Russia

Sochi, , Russia

Syktyvkar, , Russia

Yekaterinburg, , Russia

Goyang-si, , South Korea

Seoul, , South Korea

Barcelona, , Spain

Madrid, , Spain

Palma de Mallorca, , Spain

Salamanca, , Spain

Valencia, , Spain

Gothenburg, , Sweden

Lund, , Sweden

Stockholm, , Sweden

Umeå, , Sweden

Uppsala, , Sweden

Tainan City, , Taiwan

Taipei, , Taiwan

Taoyuan District, , Taiwan

Cherkassy, , Ukraine

Dnipro, , Ukraine

Donetsk, , Ukraine

Khmelnitskiy, , Ukraine

Kiev, , Ukraine

Lviv, , Ukraine

Birmingham, , United Kingdom

Harrow, , United Kingdom

Leeds, , United Kingdom

Liverpool, , United Kingdom

London, , United Kingdom

Manchester, , United Kingdom

Plymouth, , United Kingdom

Southampton, , United Kingdom

Countries

Belgium; Brazil; Canada; Chile; Colombia; Czechia; France; Germany; Hungary; Ireland; Mexico; Netherlands; Poland; Portugal; Russia; South Korea; Spain; Sweden; Taiwan; Ukraine; United Kingdom

References

Brown JR, Moslehi J, O'Brien S, Ghia P, Hillmen P, Cymbalista F, Shanafelt TD, Fraser G, Rule S, Kipps TJ, Coutre S, Dilhuydy MS, Cramer P, Tedeschi A, Jaeger U, Dreyling M, Byrd JC, Howes A, Todd M, Vermeulen J, James DF, Clow F, Styles L, Valentino R, Wildgust M, Mahler M, Burger JA. Characterization of atrial fibrillation adverse events reported in ibrutinib randomized controlled registration trials. Haematologica. 2017 Oct;102(10):1796-1805. doi: 10.3324/haematol.2017.171041. Epub 2017 Jul 27.

Reference Type: DERIVED

PMID: 28751558 (View on PubMed)

Dreyling M, Jurczak W, Jerkeman M, Silva RS, Rusconi C, Trneny M, Offner F, Caballero D, Joao C, Witzens-Harig M, Hess G, Bence-Bruckler I, Cho SG, Bothos J, Goldberg JD, Enny C, Traina S, Balasubramanian S, Bandyopadhyay N, Sun S, Vermeulen J, Rizo A, Rule S. Ibrutinib versus temsirolimus in patients with relapsed or refractory mantle-cell lymphoma: an international, randomised, open-label, phase 3 study. Lancet. 2016 Feb 20;387(10020):770-8. doi: 10.1016/S0140-6736(15)00667-4. Epub 2015 Dec 7.

Reference Type: DERIVED

PMID: 26673811 (View on PubMed)

Other Identifiers

PCI-32765MCL3001

Identifier Type: OTHER

Identifier Source: secondary_id

2012-000601-74

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1135-6930

Identifier Type: OTHER

Identifier Source: secondary_id

CR100848

Identifier Type: -

Identifier Source: org_study_id