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

NCT01646021 | Completed Phase 3 Results DMC FDA Drug

• 4 other identifiers: CR100848PCI-32765MCL30012012-000601-74U1111-1135-6930
• Study Type: interventional
• Target: 280
• Locations: 21 countries
• Sites: 92

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.

Conditions

Mantle Cell Lymphoma

Keywords

Mantle cell lymphoma; Relapsed mantle cell lymphoma; Refractory mantle cell lymphoma; Ibrutinib; Bruton's tyrosine kinase inhibitor; Temsirolimus

Outcome Measures

Primary Outcomes (1)

• Progression Free Survival (PFS)

  PFS is defined as the duration in months from the date of randomization to the date of progression disease (PD) or relapse from complete response (CR) or death whichever was reported first and was assessed based on the investigator assessment. Revised Response Criteria for Malignant Lymphoma categorizes the response of the treatment of a patient's tumour to CR (the disappearance of all evidence of disease), Relapsed Disease or PD (Any new lesion or increase by greater than or equal to \[\>=\] 50 percent \[%\] of previously involved sites from nadir).

  Time from the date of randomization until the date of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death, whichever occurred first (approximately 48 months)

Secondary Outcomes (7)

• Overall Response Rate (ORR)

  Approximately up to 48 months

• Overall Survival (OS)

  Approximately up to 48 months

• Duration of Response

  Approximately up to 48 months

• Time-to-Next Treatment

  Approximately up to 48 months

• Progression-Free Survival 2

  Approximately up to 48 months

Other Outcomes (9)

• Time to Response

  Approximately up to 2.8 years

• Extent of Exposure of Time

  Approximately up to 46.8 months

• One Year Survival Rate

  Month 12

Study Arms (2)

Ibrutinib

EXPERIMENTAL

Drug: Ibrutinib

Temsirolimus

EXPERIMENTAL

Drug: Temsirolimus

Interventions

Ibrutinib DRUG

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

Ibrutinib

Temsirolimus 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

Temsirolimus

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

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

Study Sites (92)

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Antwerp, Belgium

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Bruges, Belgium

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Brussels, Belgium

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Edegem, Belgium

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Ghent, Belgium

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Leuven, Belgium

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Wilrijk, Belgium

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Goiânia, Brazil

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Porto Alegre, Brazil

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Ribeirão Preto, Brazil

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Rio de Janeiro, Brazil

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São Paulo, Brazil

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Edmonton, Alberta, Canada

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Ottawa, Ontario, Canada

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Montreal, Quebec, Canada

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Temuco, Chile

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Bogotá, Colombia

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Medellín, Colombia

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Brno, Czechia

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Prague, Czechia

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Mulhouse, France

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Paris, France

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Pessac, France

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Villejuif, France

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Berlin, Germany

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Cologne, Germany

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Essen, Germany

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Heidelberg, Germany

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Homburg, Germany

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Kiel, Germany

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Mainz, Germany

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München, Germany

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Ulm, Germany

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Budapest, Hungary

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Debrecen, Hungary

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Pécs, Hungary

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Szeged, Hungary

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Dublin, Ireland

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Monterrey, Mexico

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Oaxaca City, Mexico

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Querétaro, Mexico

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Amsterdam, Netherlands

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Rotterdam, Netherlands

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Brzozów, Poland

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Chorzów, Poland

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Gdansk, Poland

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Krakow, Poland

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Opole, Poland

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Słupsk, Poland

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Wroclaw, Poland

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Coimbra, Portugal

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Lisbon, Portugal

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Porto, Portugal

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Chelyabinsk, Russia

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Krasnodar, Russia

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Moscow, Russia

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Nizhny Novgorod, Russia

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Obninsk, Russia

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Rostov-on-Don, Russia

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Saint Petersburg, Russia

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Sochi, Russia

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Syktyvkar, Russia

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Yekaterinburg, Russia

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Goyang-si, South Korea

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Seoul, South Korea

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Barcelona, Spain

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Madrid, Spain

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Palma de Mallorca, Spain

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Salamanca, Spain

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Valencia, Spain

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Gothenburg, Sweden

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Lund, Sweden

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Stockholm, Sweden

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Umeå, Sweden

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Uppsala, Sweden

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Tainan, Taiwan

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Taipei, Taiwan

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Taoyuan District, Taiwan

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Cherkassy, Ukraine

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Dnipro, Ukraine

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Donetsk, Ukraine

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Khmelnitskiy, Ukraine

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Kiev, Ukraine

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Lviv, Ukraine

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Birmingham, United Kingdom

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Harrow, United Kingdom

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Leeds, United Kingdom

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Liverpool, United Kingdom

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London, United Kingdom

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Manchester, United Kingdom

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Plymouth, United Kingdom

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Southampton, United Kingdom

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Related Publications (2)

• 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.

  PMID: 28751558 DERIVED

• 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.

  PMID: 26673811 DERIVED

MeSH Terms

Conditions

Lymphoma, Mantle-Cell

Interventions

ibrutinib; temsirolimus

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

Results Point of Contact

• Title: Director, Clinical Research
• Organization: Janssen-Cilag International NV

ClinicalTrialDisclosure@its.jnj.com

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 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 18, 2012
• First Posted: July 20, 2012
• Study Start: December 10, 2012
• Primary Completion: June 5, 2015
• Study Completion: December 15, 2016
• Last Updated: January 19, 2018
• Results First Posted: March 1, 2017

Record last verified: 2017-12

Locations

BE (7); CO (2); CA (3); KR (2); NL (2); DE (9); ES (5); HU (4); CZ (2); ME (3); FR (4); IE (1); PL (7); PT (3); SE (5); GB (8); CL (1); TW (3); BR (5); RU (10); UA (6)