Condition category
Cancer
Date applied
21/10/2015
Date assigned
21/10/2015
Last edited
28/01/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Contact information

Type

Public

Primary contact

Mrs Margie Berrow

ORCID ID

Contact details

Peninsula Clinical Trials Unit (PenCTU)
Room N16
ITTC Building 1
Plymouth Science Park
Plymouth
PL6 8BX
United Kingdom

Additional identifiers

EudraCT number

2015-000832-13

ClinicalTrials.gov number

Protocol/serial number

19626

Study information

Scientific title

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

Acronym

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

15/WM/0268

Study design

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

Primary study design

Interventional

Secondary study design

Randomised parallel trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

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

Condition

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

Intervention

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

Other

Phase

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

01/01/2015

Overall trial end date

01/12/2022

Reason abandoned

Eligibility

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

Patient

Age group

Adult

Gender

Both

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

24/11/2015

Recruitment end date

24/11/2019

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Derriford Hospital (lead hospital)
Derriford Road
Plymouth
PL6 8DH
United Kingdom

Sponsor information

Organisation

Plymouth Hospitals NHS Trust

Sponsor details

Research Office
Level 2
MSCP
Bircham Park Offices
Morlaix Drive
Plymouth
PL6 8BQ
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Charity

Funder name

Cancer Research UK

Alternative name(s)

CRUK

Funding Body Type

private sector organisation

Funding Body Subtype

other non-profit

Location

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 www.mantlecelllymphoma.org.uk

Intention to publish date

01/12/2023

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.