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Mantle Cell LymphomaPhase 3NCT01646021

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

A Phase 3 study testing Ibrutinib and Temsirolimus in people with Mantle Cell Lymphoma, run by Janssen Research & Development, LLC at 92 sites in 21 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Mantle Cell Lymphoma
What is being tested?
Ibrutinib and Temsirolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
280 participants
Where
92 sitesin 21 countries
Study dates
10 Dec 2012to 15 Dec 2016
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 12Show fewer
  • 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

Trial locations and contacts

92 sites in 21 countries.

92 sites in 21 countries

Russia10 sites

  • Study site

    Chelyabinsk

  • Study site

    Krasnodar

  • Study site

    Moscow

  • Study site

    Nizhny Novgorod

  • Study site

    Obninsk

  • Study site

    Rostov-on-Don

  • Study site

    Saint Petersburg

  • Study site

    Sochi

  • Study site

    Syktyvkar

  • Study site

    Yekaterinburg

Other trials in Russia

Germany9 sites

  • Study site

    Berlin

  • Study site

    Cologne

  • Study site

    Essen

  • Study site

    Heidelberg

  • Study site

    Homburg

  • Study site

    Kiel

  • Study site

    Mainz

  • Study site

    München

  • Study site

    Ulm

Other trials in Germany

United Kingdom8 sites

  • Study site

    Birmingham

  • Study site

    Harrow

  • Study site

    Leeds

  • Study site

    Liverpool

  • Study site

    London

  • Study site

    Manchester

  • Study site

    Plymouth

  • Study site

    Southampton

Other trials in United Kingdom

Belgium7 sites

  • Study site

    Antwerp

  • Study site

    Bruges

  • Study site

    Brussels

  • Study site

    Edegem

  • Study site

    Ghent

  • Study site

    Leuven

  • Study site

    Wilrijk

Other trials in Belgium

Poland7 sites

  • Study site

    Brzozów

  • Study site

    Chorzów

  • Study site

    Gdansk

  • Study site

    Krakow

  • Study site

    Opole

  • Study site

    Słupsk

  • Study site

    Wroclaw

Other trials in Poland

Ukraine6 sites

  • Study site

    Cherkassy

  • Study site

    Dnipro

  • Study site

    Donetsk

  • Study site

    Khmelnitskiy

  • Study site

    Kiev

  • Study site

    Lviv

Other trials in Ukraine

Brazil5 sites

  • Study site

    Goiânia

  • Study site

    Porto Alegre

  • Study site

    Ribeirão Preto

  • Study site

    Rio de Janeiro

  • Study site

    São Paulo

Other trials in Brazil

Spain5 sites

  • Study site

    Barcelona

  • Study site

    Madrid

  • Study site

    Palma de Mallorca

  • Study site

    Salamanca

  • Study site

    Valencia

Other trials in Spain

Sweden5 sites

  • Study site

    Gothenburg

  • Study site

    Lund

  • Study site

    Stockholm

  • Study site

    Umeå

  • Study site

    Uppsala

Other trials in Sweden

France4 sites

  • Study site

    Mulhouse

  • Study site

    Paris

  • Study site

    Pessac

  • Study site

    Villejuif

Other trials in France

Hungary4 sites

  • Study site

    Budapest

  • Study site

    Debrecen

  • Study site

    Pécs

  • Study site

    Szeged

Other trials in Hungary

Canada3 sites

  • Study site

    Edmonton, Alberta

  • Study site

    Montreal, Quebec

  • Study site

    Ottawa, Ontario

Other trials in Canada

Mexico3 sites

  • Study site

    Monterrey

  • Study site

    Oaxaca City

  • Study site

    Querétaro

Other trials in Mexico

Portugal3 sites

  • Study site

    Coimbra

  • Study site

    Lisbon

  • Study site

    Porto

Other trials in Portugal

Taiwan3 sites

  • Study site

    Tainan

  • Study site

    Taipei

  • Study site

    Taoyuan

Other trials in Taiwan

Colombia2 sites

  • Study site

    Bogotá

  • Study site

    Medellín

Other trials in Colombia

Czechia2 sites

  • Study site

    Brno

  • Study site

    Prague

Other trials in Czechia

Netherlands2 sites

  • Study site

    Amsterdam

  • Study site

    Rotterdam

Other trials in Netherlands

South Korea2 sites

  • Study site

    Goyang-si

  • Study site

    Seoul

Other trials in South Korea

Chile1 site

  • Study site

    Temuco

Other trials in Chile

Ireland1 site

  • Study site

    Dublin

Other trials in Ireland

About this study

Official title: A Randomized, Controlled, Open-Label, Multicenter Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, Versus Temsirolimus in Subjects With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy

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.

Read the 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.

Being tested
Ibrutinib, Temsirolimus
Keywords
Mantle cell lymphoma, Relapsed mantle cell lymphoma, Refractory mantle cell lymphoma, Ibrutinib, Bruton's tyrosine kinase inhibitor, Temsirolimus
Medical subject headings
Lymphoma, Mantle-Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • IbrutinibDrug

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

  • TemsirolimusDrug

    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

Study groups in NCT01646021
Study groupRoleWhat they receive
IbrutinibExperimentalNot described
Receives: Drug: Ibrutinib
TemsirolimusExperimentalNot described
Receives: Drug: Temsirolimus

What is being measured

The primary outcome is the main question the study is designed to answer.

  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).

    Measured: 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)

  1. Overall Response Rate (ORR)

    ORR is defined as the percentage of participants who achieved either CR or PR as best overall response based on the investigator assessment. CR is Disappearance of all target lesions while PR is greater than or equal to 30 % decrease in the sum of the longest diameter of target lesions and Overall Response (OR) is sum of CR and PR.

    Measured: Approximately up to 48 months

  2. Overall Survival (OS)

    Overall survival (OS) was defined as the interval between the date of randomization and the date of death from any cause.

    Measured: Approximately up to 48 months

  3. Duration of Response

    Duration of response (CR or PR), defined as the duration in days from the date of initial response to the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death. The analysis was based on the investigator assessment.

    Measured: Approximately up to 48 months

  4. Time-to-Next Treatment

    Time to next treatment was measured from the date of randomization to the start date of any anti-neoplastic treatment subsequent to study treatment.

    Measured: Approximately up to 48 months

  5. Progression-Free Survival 2

    Progression-free survival 2 defined as the time interval between the date of randomization and date of event, defined as progressive disease as assessed by investigator that started after the next line of subsequent anti-neoplastic therapy (including cross-over to ibrutinib), death from any cause, or the start of the second subsequent anti-neoplastic therapy if no progressive disease was recorded after the first subsequent anti-neoplastic therapy.

    Measured: Approximately up to 48 months

  6. Time to Worsening in the Lymphoma Sub Scale of Functional Assessment of Cancer Therapy- Lymphoma (FACT-Lym)

    Time to worsening in the Lymphoma subscale of the FACT-Lym, defined as the interval from the date of randomization to the start date of worsening. Worsening was defined by a 5-point decrease from baseline. FACT-Lym Lymphoma subscale contains 15 questions, scores from 0 to 4 for each question (higher the worse). Lymphoma subscale score is the total of reverse scores, range 0 to 60. Higher scores indicate a better quality of life.

    Measured: Approximately up to 48 months

  7. Number of Participants Affected With Treatment-emergent Adverse Events

    An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.

    Measured: Time from first dose of study drug until the last dose date + 30 days or the start of a subsequent anti-neoplastic therapy, whichever occur earlier (Approximately up to 4 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Jul 2012 (estimated)
  2. Study start10 Dec 2012
  3. Primary completion5 Jun 2015
  4. Study completion15 Dec 2016

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
280 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01646021
Sponsor's protocol ID
CR100848
Other IDs
PCI-32765MCL3001, 2012-000601-74, U1111-1135-6930
Status last verified
Dec 2017
First submitted
18 Jul 2012
Last updated
19 Jan 2018
Data monitoring committee
Yes
FDA-regulated drug
Yes

Publications

  • 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.

    PubMed 28751558

  • 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.

    PubMed 26673811

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Ibrutinib and Temsirolimus in people with Mantle Cell Lymphoma, run by Janssen Research & Development, LLC at 92 sites in 21 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 19 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 92 sites in Russia, Germany, United Kingdom, Belgium, Poland and 16 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression Free Survival (PFS) (time frame: 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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01646021, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2018.

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