ENRICH Ibrutinib for untreated mantle cell lymphoma
| ISRCTN | ISRCTN11038174 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN11038174 |
| EudraCT/CTIS number | 2015-000832-13 |
| Secondary identifying numbers | 19626 |
- Submission date
- 21/10/2015
- Registration date
- 21/10/2015
- Last edited
- 23/07/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English Summary
Contact information
Ms Claire Scully
Public
Public
Peninsula Clinical Trials Unit
Faculty of Health
University of Plymouth
Plymouth
PL6 8BX
United Kingdom
| Phone | +44 1752 437513 |
|---|---|
| enrich@plymouth.ac.uk |
Dr Jeanette Sanders
Scientific
Scientific
Peninsula Clinical Trials Unit
Faculty of Health
University of Plymouth
Room N16, ITTC 1 Building
Plymouth Science Park
Plymouth
PL6 8BX
United Kingdom
| Phone | +44 (0)1752 315246 |
|---|---|
| jeanette.sanders@plymouth.ac.uk |
Study information
| Study design | Multi-centre open-label integrated phase II/III randomised parallel trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| 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(s) | 15/WM/0268 |
| Condition | Mantle cell lymphoma (MCL) |
| Intervention | Current intervention as of 18/04/2023: 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 2 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 2 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 8 weeks 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. _____ Previous 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 | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase II/III |
| Drug / device / biological / vaccine name(s) | Ibrutinib, rituximab, bendamustine, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) |
| Primary outcome measure | Current primary outcome measure as of 18/04/2023: Progression-free survival is determined at 2.5 years. This is defined as the interval from the date of randomisation to the earlier of the first documentation of disease progression/relapse or death from any cause. Previous primary outcome measure: 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 | Current secondary outcome measures as of 18/04/2023: 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 by CT scans and bone marrow biopsies at baseline, 12 weeks, 24 weeks and every 6 months thereafter until the end of the study 3. Minimal residual disease (MRD) using flow cytometry at end of study 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, mid-treatment, end of treatment and end of maintenance 6. 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. _____ Previous 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 study start date | 01/01/2015 |
| Overall study end date | 31/12/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 400; UK Sample Size: 400 |
| Participant inclusion criteria | Current inclusion criteria as of 18/04/2023: 1. Male/female patients aged 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 >1.0 x 10(9)/L or platelets >100 x 10(9)/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 >30 mL/min 10. Cardiac function sufficient to tolerate either rituximab-CHOP or rituximab-bendamustine chemotherapy 11. Able to give voluntary written informed consent 12. Willingness and ability to take Pneumocystis jiroveci pneumonia prophylaxis _____ Previous 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 exclusion criteria | Current exclusion criteria as of 18/04/2023: 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 4 weeks prior to Day 1 of Cycle 1 4. Major surgery within 2 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 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 11. CNS involvement of MCL _____ Previous 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 | 30/06/2021 |
Locations
Countries of recruitment
- Denmark
- England
- Finland
- Norway
- Sweden
- United Kingdom
Study participating centre
Derriford Hospital (lead hospital)
Derriford Road
Plymouth
PL6 8DH
United Kingdom
Plymouth
PL6 8DH
United Kingdom
Sponsor information
University Hospitals Plymouth NHS Trust
Hospital/treatment centre
Hospital/treatment centre
Research Office
Level 2 MSCP, Bircham Park Offices
1 Roscoff Rise
Derriford
Plymouth
PL6 5FP
England
United Kingdom
| Phone | +44 (0)1752 432842 |
|---|---|
| plh-tr.RD-Office@nhs.net | |
| Website | http://www.plymouthhospitals.nhs.uk/home |
"ROR" |
https://ror.org/05x3jck08 |
Funders
Funder type
Charity
Cancer Research UK
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Alternative name(s)
- CR_UK, Cancer Research UK - London, CRUK
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/12/2024 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| 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 |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are/will be available upon request from penctudata@plymouth.ac.uk. The data will be made available after publication. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
23/07/2024: The following changes were made:
1. The overall study end date was changed from 30/06/2024 to 31/12/2026.
2. The Individual participant data (IPD) sharing plan and summary were added.
3. Study website was added.
12/12/2023: The intention to publish date was changed from 01/12/2023 to 31/12/2024.
18/04/2023: The following changes have been made:
1. The recruitment end date has been changed from 31/03/2021 to 30/06/2021.
2. The overall trial end date has been changed from 01/12/2022 to 30/06/2024.
3. The public contact has been changed.
4. The intervention has been changed.
5. The primary outcome measure has been changed.
6. The secondary outcome measures have been changed.
7. The participant inclusion criteria have been changed.
8. The participant exclusion criteria have been changed.
9. Sweden, Denmark, Finland and Norway have been added to the countries of recruitment.
10. The sponsor has been changed from Plymouth Hospitals NHS Trust to University Hospitals Plymouth NHS Trust.
11. The scientific contact has been added.
07/01/2021: The following changes were made to the trial record:
1. The contact details were updated.
2. The recruitment end date was changed from 24/11/2019 to 31/03/2021.
3. The sponsor details were updated.
02/04/2019: The condition has been changed from "Topic: Cancer; Subtopic: Lymphoma; Disease: Lymphoma (Non Hodgkins - aggressive)" to "Mantle cell lymphoma" following a request from the NIHR.
28/01/2016: Plain English summary link added.
