A trial of CHOP-R therapy, with or without acalabrutinib, in patients with newly diagnosed Richter's Syndrome
| ISRCTN | ISRCTN52839057 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN52839057 |
| EudraCT/CTIS number | 2017-004401-40 |
| ClinicalTrials.gov number | NCT03899337 |
| Secondary identifying numbers | 38923 |
- Submission date
- 18/02/2019
- Registration date
- 04/03/2019
- Last edited
- 14/05/2024
- 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
Miss Sophie Cramp
Scientific
Scientific
STELLAR Trial Coordinator
STELLAR Trial Office
TAP Haematology Clinical Trials Team
Centre for Clinical Haematology
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
| Phone | +44 (0)1213717867 |
|---|---|
| STELLAR@trials.bham.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Treatment, Drug |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet |
| Scientific title | STELLAR: A phase II, randomiSed study of CHOP-R in combination with acalabruTinib comparEd to CHOP-R in patients with newLy diagnosed Richter’s Syndrome (RS) and a pLAtfoRm for initial investigations into activity of novel treatments in relapsed/refractory and newly diagnosed RS |
| Study acronym | STELLAR |
| Study hypothesis | Adding acalabrutinib to CHOP-R treatment will improve progression-free survival rates for patients with newly diagnosed Richter’s Syndrome. |
| Ethics approval(s) |
Approved 31/01/2019, South Central – Oxford B REC (Whitefriars, Level 3, Block B, Lewin’s Mead, Bristol, BS1 2NT, United Kingdom; +44 (0)207 1048058; nrescommittee.southcentral-oxfordb@nhs.net), ref: 18/SC/0634 |
| Condition | Richter syndrome |
| Intervention | Participants who have Richter’s Syndrome and are suitable for CHOP-R will be recruited by specialised hospitals across the UK. People with another cancer, heart problems, or recent stroke cannot take part. Participants will have a lymph node biopsy, 3-4 bone marrow biopsies, blood samples, and PET-CT and CT scans. Randomised Trial Component: Patients will be randomised 1:1 to either treatment with CHOP-R (Standard of Care [SoC]) or CHOP-R + acalabrutinib (Experimental). The induction treatment (CHOP-R) will continue for up to 6 cycles (each cycle is 21 days), and will be given according to the following schedule: Rituximab, 375 mg/m2, IV infusion, OD, 6 cycles, days of cycle: 1 Cyclophosphamide, 750 mg/m2, IV bolus, OD, 6 cycles, days of cycle: 1 Doxorubicin, 50 mg/m2, IV bolus, OD, 6 cycles, days of cycle: 1 Vincristine, 1.4 mg/m2, IV infusion, OD, 6 cycles, days of cycle: 1 Prednisolone, 40 mg/m2, PO, OD, 6 cycles, days of cycle: 1-5 Acalabrutinib, 100 mg, PO, BD, 6 cycles, continuous thereafter until disease progression toxicity, patient choice or death, days of cycle: 6-21 Patients will be followed up for 2 year survival data. Single-Arm Platform Studies: Cohort 1: Patients registered to Cohort 1 will receive 100 mg acalabrutinib monotherapy, twice daily, continuously from day 1 until disease progression, toxicity, patient choice or death. Patients will be followed up for 2 year survival data. Cohort 2: Patients registered to Cohort 2 will receive CHOP-R + acalabrutinib. The induction treatment (CHOP-R) will continue for up to 6 cycles (each cycle is 21 days), and will be given according to the following schedule: Rituximab, 375 mg/m2, IV infusion, OD, 6 cycles, days of cycle: 1 Cyclophosphamide, 750 mg/m2, IV bolus, OD, 6 cycles, days of cycle: 1 Doxorubicin, 50 mg/m2, IV bolus, OD, 6 cycles, days of cycle: 1 Vincristine, 1.4 mg/m2, IV infusion, OD, 6 cycles, days of cycle: 1 Prednisolone, 40 mg/m2, PO, OD, 6 cycles, days of cycle: 1-5 Acalabrutinib, 100 mg, PO, BD, 6 cycles, continuous thereafter until disease progression toxicity, patient choice or death, days of cycle: 6-21 Patients will be followed up for 2 year survival data. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Not Applicable |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | Acalabrutinib, doxorubicin, vincristine, cyclophosphamide, rituximab, prednisolone |
| Primary outcome measure | Progression free survival (PFS); Timepoint(s): Time from randomisation to the date of progression or death from any cause. |
| Secondary outcome measures | 1. Overall survival (OS) defined as time from date of randomisation (for randomised trial) or registration (to the relevant cohort for single-arm cohorts) to date of death from any cause 2. Overall response (randomised component only) after cycle 6, defined by the modified Cheson criteria 3. Overall response (cohorts 1 only) after 12 weeks, defined by the modified Cheson criteria 4. PFS (single-arm cohorts only) defined as the time from date of registration to date of progression or death from any cause 5. Quality of life assessed using ECOG performance status and the CLL17 and NHLHG29 questionnaires at the end of cycles 4 and 6 for participants receiving CHOP-R as part of their treatment (randomised cohorts and Cohort 2), and at 12 and 24 weeks for participants receiving acalabrutinib monotherapy (Cohort 1) 6. Toxicity defined as the number of participants who experience one or more adverse event grade 3 or higher or serious adverse event of any grade, recorded from start of treatment until 28 days after the last administration of study drug. 7. Proportion of participants proceeding to allogeneic or autologous stem cell transplantation, measured as number of patients proceeding to transplant on each treatment arm, at confirmation of partial or complete remission |
| Overall study start date | 26/11/2016 |
| Overall study end date | 31/05/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 16 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 84; UK Sample Size: 84 |
| Participant inclusion criteria | Inclusion criteria for the Randomised Trial: 1. Suitable for anthracycline-containing chemo-immunotherapy 2. Patients with CLL and newly diagnosed biopsy proven DLBCL-type RS 3. ECOG performance status of 0, 1, 2 or 3 4. Age 16 years and over 5. Signed written informed consent prior to performing any study-specific procedures Inclusion criteria Cohort 1 (progressive RS following chemo-immunotherapy): 1. Patients with relapsed/refractory RS who received anthracycline based chemotherapy with anti-CD20 monoclonal antibody 2. ECOG performance status of 0, 1, 2 or 3 3. Age 16 years and over 4. Signed written informed consent prior to performing any study-specific procedures Inclusion criteria Cohort 2 (anthracycline-naïve RS patients, diagnosed while on ibrutinib): 1. Ibrutinib-exposed CLL patients who have developed biopsy-proven DLBCL-type RS within four weeks of last dose of ibrutinib 2. No previous anthracycline treatment and suitable for anthracycline-containing chemo-immunotherapy 3. Patients with CLL and newly diagnosed biopsy proven DLBCL-type RS 4. ECOG performance status of 0, 1, 2 or 3 5. Age 16 years and over 6. Signed written informed consent prior to performing any study-specific procedures |
| Participant exclusion criteria | Exclusion criteria ALL: 1. Known central nervous system (CNS) involvement of CLL or DLBCL 2. Any other active malignancy that requires active treatment, with the exception of basal cell carcinoma, in-situ cervical cancer, and non-invasive squamous cell carcinoma of the skin 3. Chronic or ongoing active infectious disease 4. Positive serology for Hepatitis B (HBKnown human immunodeficiency virus (HIV) positive 5. Patients with active bleeding or history of bleeding diathesis (e.g. haemophilia, von Willebrand disease) 6. Patients receiving therapeutic anticoagulation with warfarin or equivalent (e.g. phenoprocoumon) 7. Uncorrected prolonged prothrombin time (PT) or an activated partial thromboplastin time (APTT) > 2 x the upper limit of normal (ULN) 8. Major surgery within 30 days prior to randomisation and/or inadequate recovery from any prior major surgery, toxicity or complications 9. Patients with malabsorption syndrome or medical conditions significantly affecting gastrointestinal function 10. Clinically significant cardiac disease including unstable angina, uncontrolled congestive heart failure, and unstable arrhythmias requiring therapy, with the exception of extra systoles or minor conduction abnormalities 11. Significant concurrent, uncontrolled severe medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease 12. History of significant cerebrovascular disease in the 6 months prior to randomisation, including intracranial haemorrhage 13. Known or suspected hypersensitivity to components of the investigational products 14. Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to proposed start of treatment 15. Current participation in any other interventional clinical study 16. Patients known or suspected of not being able to comply with a study 17. Breastfeeding women or women with a positive pregnancy test at screening 18. Women of childbearing potential and men not willing to use adequate contraception during study and for 3 months after last dose of study therapy Additional exclusion criteria for the Randomised Trial: 1. Prior therapy with CHOP or any anthracycline containing treatment at any time prior to randomisation 2. Ibrutinib-exposed CLL patients who have been newly diagnosed with RS within four weeks of their last dose of ibrutinib. (Ibrutinib-exposed CLL patients who discontinue ibrutinib due to toxicity or progressive CLL and later (more than four weeks) develop RS are not excluded from the randomised trial component) 3. Previous acalabrutinib exposure Additional exclusion criteria for Cohort 1 (progressive RS following chemo-immunotherapy): 1. Previous acalabrutinib exposure Additional exclusion criteria for Cohort 2 (anthracycline-naïve RS patients, diagnosed while on ibrutinib): 1. Prior therapy with CHOP or any anthracycline containing treatment at any time prior to randomisation 2. Previous acalabrutinib exposure |
| Recruitment start date | 31/03/2019 |
| Recruitment end date | 31/05/2025 |
Locations
Countries of recruitment
- England
- Northern Ireland
- Scotland
- United Kingdom
- Wales
Study participating centres
Churchill Hospital
Old Road
Oxford
OX3 7LJ
United Kingdom
Oxford
OX3 7LJ
United Kingdom
Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom
Glasgow
G12 0YN
United Kingdom
Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
United Kingdom
Belfast
BT9 7AB
United Kingdom
The Clatterbridge Cancer Centre
Clatterbridge Rd
Bebington
Birkenhead
Wirral
CH63 4JY
United Kingdom
Bebington
Birkenhead
Wirral
CH63 4JY
United Kingdom
Christie Hospital
Wilmslow Road
Manchester
M20 4BX
United Kingdom
Manchester
M20 4BX
United Kingdom
King’s College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom
London
SE5 9RS
United Kingdom
Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom
Leicester
LE1 5WW
United Kingdom
Nottingham City Hospital
City Hospital Campus
Nottingham
NG5 1PB
United Kingdom
Nottingham
NG5 1PB
United Kingdom
Royal Bournemouth Hospital
Bournemouth
BH7 7DW
United Kingdom
BH7 7DW
United Kingdom
Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom
Sheffield
S10 2JF
United Kingdom
Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom
Southampton
SO16 6YD
United Kingdom
St Bartholomew’s Hospital
West Smithfield
London
EC1A 7BE
United Kingdom
London
EC1A 7BE
United Kingdom
St James’ University Hospital
Beckett St
Leeds
LS9 7TF
United Kingdom
Leeds
LS9 7TF
United Kingdom
The Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom
Birmingham
B15 2TH
United Kingdom
University College London Hospital
235 Euston Road
London
NW1 2BU
United Kingdom
London
NW1 2BU
United Kingdom
University Hospital of Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom
Cardiff
CF14 4XW
United Kingdom
Sponsor information
University of Birmingham
University/education
University/education
Research Support Group
Aston Webb Building
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
| Phone | +44 (0)121 414 2644 |
|---|---|
| researchgovernance@contacts.bham.ac.uk | |
"ROR" |
https://ror.org/03angcq70 |
Funders
Funder type
Industry
Acerta Pharma
No information available
Bloodwise; Grant Codes: 17003
Private sector organisation / Other non-profit organizations
Private sector organisation / Other non-profit organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 31/05/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Data sharing statement to be made available at a later date |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal in 2025. |
| IPD sharing plan | The data sharing plans for the current study are unknown and will be made available at a later date. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | protocol | 20/05/2019 | 22/05/2019 | Yes | No |
| HRA research summary | 28/06/2023 | No | No |
Editorial Notes
14/05/2024: The recruitment end date has been changed from 31/05/2024 to 31/05/2025.
11/04/2024: The ClinicalTrials.gov number was added.
01/11/2023: The following changes have been made:
1. Drug/device/biological/vaccine name(s) were added.
2. The overall study end date was changed from 31/05/2026 to 31/05/2027.
3. The intention to publish date was changed from 31/05/2027 to 31/05/2028.
11/04/2022: The following changes have been made:
1. The recruitment end date has been changed from 31/03/2022 to 31/05/2024.
2. The overall trial end date has been changed from 30/11/2024 to 31/05/2026.
3. The intention to publish date has been changed from 30/11/2025 to 31/05/2027.
04/09/2020: Cancer Research UK lay summary link added to plain English summary field.
10/06/2020: Recruitment has resumed.
24/04/2020: Due to current public health guidance, recruitment for this study has been paused.
05/08/2019: Internal review.
21/06/2019: Internal review.
22/05/2019: Publication reference added.
05/04/2019: Internal review.
22/03/2019: The condition has been changed from "Specialty: Cancer, Primary sub-specialty: Haematological Oncology; Health Category: Cancer and neoplasms; Disease/Condition: Malignant neoplasms, stated or presumed to be primary, of lymphoid, haematopoietic and related tissue" to "Richter syndrome" following a request from the NIHR.
27/02/2019: Trial's existence confirmed by the NIHR.
