Condition category
Date applied
Date assigned
Last edited
Prospectively registered
Overall trial status
Recruitment status

Contact information



Primary contact

Mrs Margie Berrow


Contact details

Peninsula Clinical Trials Unit (PenCTU)
Room N16
ITTC Building 1
Plymouth Science Park
United Kingdom

Additional identifiers

EudraCT number

2015-000832-13 number

Protocol/serial number


Study information

Scientific title

Randomised, open label study of rituximab/ibrutinib vs rituximab/chemotherapy in older patients with untreated mantle cell lymphoma


Study hypothesis

The aim of this study is to compare the effect on progression-free survival of treatment with ibrutinib given in combination with rituximab (IR) against treatment with standard chemotherapy given in combination with rituximab.

Ethics approval


Study design

Multi-centre open-label integrated phase II/III randomised parallel trial

Primary study design


Secondary study design

Randomised parallel trial

Trial setting


Trial type


Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet


Topic: Cancer; Subtopic: Lymphoma; Disease: Lymphoma (Non Hodgkins - aggressive)


Participants are randomly allocated to one of two treatment groups:

Group 1: Participants receive daily ibrutinib in combination with 6 or 8 cycles of rituximab, followed by daily ibrutinib in combination with rituximab maintenance for two years, and daily ibrutinib during the follow up period until disease progression or the end of the study. 126 weeks (2.5 years) of IR however ibrutinib continues until disease progression or end of study.

Group 2: Participants undergo 6-8 cycles of chemotherapy (either CHOP or Bendamustine at clinician’s discretion) in combination with rituximab, followed by rituximab maintenance for two years. No further treatment after the maintenance period. 126 weeks (2.5 years)

Participants in the control arm will be seen every 3-4 weeks during the chemotherapeutic period and every 2 months whilst receiving rituximab maintenance. This follow up will be mirrored exactly for participants in the intervention arm.
In both arms, following the completion of maintenance, participants will be seen every 3 months until disease progression or end of study, as for routine clinical care.

Intervention type



Phase II/III

Drug names

Primary outcome measures

Progression Free Survival is determined at 2.5 years measured as time from randomisation to first documented evidence of disease progressions or death from any cause.

Secondary outcome measures

1. Overall Survival measured as time from randomisation to date of death from any cause is determined at the end of the study
2. Disease response is formally assessed using CT scanning at baseline, 12 weeks, 24 weeks and every 6 months thereafter until the end of the study
3. MRD using flow cytometry at 2.5 years [please expand the abbreviation “MRD”] Minimal Residual Disease
4. Safety and toxicity based on adverse events graded by Common Terminology Criteria for Adverse Event Reporting (CTCAE) v4.03 throughout participation in the study until 30 days post treatment
5. Quality of Life measured using the EORTC QLQ-30 questionnaire at baseline, 12 weeks, 24 weeks and 2.5 years
6. Cost of delivery measured by study-specific worksheets during the treatment period
7. Time to next treatment, to include date treatment begins and class of treatment. This will be measured when each participant commences their next treatment regimen, by recording the class of drug that each participant is given as their next line treatment.

Overall trial start date


Overall trial end date


Reason abandoned


Participant inclusion criteria

1. Male/female patients 60 years and over
2. Pathologically confirmed MCL, with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1
3. Stage II-IV disease, measurable by imaging and requiring treatment in the opinion of the treating clinician
4. No previous treatment for MCL (other than localised radiotherapy or 7 day pulse of steroids for symptom control)
5. Performance status ECOG 0-2
6. Absolute neutrophil count >1.0x109/L or platelets >100x109 /L independent of growth factor support or unless related to lymphoma
7. AST and/or ALT <3xULN
8. Total bilirubin ≤1.5xULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin
9. Calculated creatinine clearance >30mL/min
10. Cardiac function sufficient to tolerate 300mg/m2 of doxorubicin. A pre-treatment echocardiogram is not mandated, but recommended in patients considered at higher risk of anthracycline cardiotoxicity
11. Able to give voluntary written informed consent

Participant type


Age group




Target number of participants

Planned Sample Size: 400; UK Sample Size: 400

Participant exclusion criteria

1. Patients considered fit enough to undergo autologous or allogeneic stem cell transplant as treatment for MCL
2. Known serological positivity for HBV, HCV, HIV
3. Vaccinated with live vaccines within four weeks prior to Day 1 of Cycle 1
4. Major surgery within two weeks prior to Day 1 of Cycle 1
5. Diagnosed with or treated for any other malignancy than MCL within 2 years prior to Day 1 of Cycle 1 (except BCC, SCC or any in situ malignancy)
6. Active systemic infection requiring treatment
7. Male subjects with female partners of childbearing potential who are unwilling to use appropriate contraception methods whilst on study treatment (see section 8.4)
8. Women who are pregnant or breastfeeding
9. Serious medical or psychiatric illness likely to interfere with participation in this clinical study
10. Concurrent treatment with another investigational agent

Recruitment start date


Recruitment end date



Countries of recruitment

United Kingdom

Trial participating centre

Derriford Hospital (lead hospital)
Derriford Road
United Kingdom

Sponsor information


Plymouth Hospitals NHS Trust

Sponsor details

Research Office
Level 2
Bircham Park Offices
Morlaix Drive
United Kingdom

Sponsor type

Hospital/treatment centre



Funder type


Funder name

Cancer Research UK

Alternative name(s)


Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit


United Kingdom

Results and Publications

Publication and dissemination plan

It is likely that the results, analysis and discussion will be published in an appropriate high impact haematology specialist journal. Poster or platform presentations may be made at regional, national or international conferences as appropriate. The TMG will prepare a plain English summary of the study results which will be posted on the website

Intention to publish date


Participant level data

To be made available at a later date

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

28/01/2016: Plain English summary link added.