A trial of CHOP-R therapy, with or without acalabrutinib, in patients with newly diagnosed Richter's Syndrome

Plain English Summary

https://www.cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-of-r-chop-and-acalabrutinib-for-people-with-richters-syndrome-stellar

Study website

Type

Scientific

Contact name

Miss Sophie Cramp

ORCID ID

Contact details

STELLAR Trial Coordinator
STELLAR Trial Office
TAP Haematology Clinical Trials Team
Centre for Clinical Haematology
Queen Elizabeth Hospital
Birmingham
B15 2TH
United Kingdom
+44 (0)1213717867
STELLAR@trials.bham.ac.uk

EudraCT/CTIS number

2017-004401-40

IRAS number

ClinicalTrials.gov number

NCT03899337

Protocol/serial number

38923

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

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

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

Patient information sheet

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

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

Reason abandoned (if study stopped)

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 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 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

Countries of recruitment

England, Northern Ireland, Scotland, United Kingdom, Wales

Study participating centre

Churchill Hospital
Old Road
Oxford
OX3 7LJ
United Kingdom

Study participating centre

Beatson West of Scotland Cancer Centre
1053 Great Western Road
Glasgow
G12 0YN
United Kingdom

Study participating centre

Belfast City Hospital
Lisburn Road
Belfast
BT9 7AB
United Kingdom

Study participating centre

The Clatterbridge Cancer Centre
Clatterbridge Rd
Bebington
Birkenhead
Wirral
CH63 4JY
United Kingdom

Study participating centre

Christie Hospital
Wilmslow Road
Manchester
M20 4BX
United Kingdom

Study participating centre

King’s College Hospital
Denmark Hill
London
SE5 9RS
United Kingdom

Study participating centre

Leicester Royal Infirmary
Infirmary Square
Leicester
LE1 5WW
United Kingdom

Study participating centre

Nottingham City Hospital
City Hospital Campus
Nottingham
NG5 1PB
United Kingdom

Study participating centre

Royal Bournemouth Hospital
Bournemouth
BH7 7DW
United Kingdom

Study participating centre

Royal Hallamshire Hospital
Glossop Road
Sheffield
S10 2JF
United Kingdom

Study participating centre

Southampton General Hospital
Tremona Road
Southampton
SO16 6YD
United Kingdom

Study participating centre

St Bartholomew’s Hospital
West Smithfield
London
EC1A 7BE
United Kingdom

Study participating centre

St James’ University Hospital
Beckett St
Leeds
LS9 7TF
United Kingdom

Study participating centre

The Queen Elizabeth Hospital
Edgbaston
Birmingham
B15 2TH
United Kingdom

Study participating centre

University College London Hospital
235 Euston Road
London
NW1 2BU
United Kingdom

Study participating centre

University Hospital of Wales
Heath Park
Cardiff
CF14 4XW
United Kingdom

Organisation

University of Birmingham

Sponsor details

Research Support Group
Aston Webb Building
Edgbaston
Birmingham
B15 2TT
England
United Kingdom
+44 (0)121 414 2644
researchgovernance@contacts.bham.ac.uk

Sponsor type

University/education

Website

ROR

https://ror.org/03angcq70

Funder type

Industry

Funder name

Acerta Pharma

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Funder name

Bloodwise; Grant Codes: 17003

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

Other non-profit organizations

Location

United Kingdom

Publication and dissemination plan

Planned publication in a high-impact peer-reviewed journal in 2025.

Intention to publish date

31/05/2028

Individual participant data (IPD) sharing plan

The data sharing plans for the current study are unknown and will be made available at a later date.

IPD sharing plan summary

Data sharing statement to be made available at a later date

Study outputs