Genomic and transcriptomic correlates of Richter transformation in chronic lymphocytic leukemia.
Jenny Klintman, Niamh Appleby, Basile Stamatopoulos...
https://pubmed.ncbi.nlm.nih.gov/33206936Actively Recruiting
Phase 2
Age: 18Years +
All Genders
ID03899337
A Phase II Randomised Study of CHOP-R With or Without Acalabrutinib in Newly Diagnosed Richter's Syndrome and Platform Studies of Novel Treatments in Relapsed/Refractory Cases
Led by University of Birmingham · Updated on 2023-01-09
105
Participants Needed
16
Research Sites
82 weeks
Total Duration
On this page
Sponsors
U
University of Birmingham
Lead Sponsor
B
Bloodwise
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the addition of acalabrutinib to the standard CHOP-R chemotherapy treatment in patients newly diagnosed with Richter's Syndrome (RS), an aggressive transformation of chronic lymphocytic leukaemia (CLL). This Phase II trial also serves as a platform to test other new drugs for RS. RS is difficult to treat and often leads to a short life expectancy. The study aims to determine if acalabrutinib, which blocks a protein that helps cancer cells grow, can improve treatment outcomes when combined with CHOP-R compared to CHOP-R alone. Participants will be randomly assigned to receive either CHOP-R alone or CHOP-R plus acalabrutinib. CHOP-R treatment involves up to six cycles every 21 days, with drugs including rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone. Those receiving acalabrutinib will take 100 mg tablets twice daily at home on days 6 to 21 of each cycle and may continue acalabrutinib after completing CHOP-R. Separate cohorts will assess acalabrutinib alone in patients whose RS has progressed after CHOP-R or who were diagnosed with RS while on ibrutinib treatment. Participants undergo various assessments including lymph node and bone marrow biopsies, blood tests, PET-CT and CT scans, and quality of life questionnaires. They are monitored frequently during treatment for side effects and response, with formal assessments after 4 and 6 treatment cycles. Follow-up continues for at least two years to evaluate progression-free survival and overall health. The study includes safety monitoring and may offer stem cell transplantation for suitable patients responding to treatment.
CONDITIONS
Brief Title
A Trial of CHOP-R Therapy, With or Without Acalabrutinib, in Patients With Newly Diagnosed Richter's Syndrome
Who Can Participate
Age: 18Years +
All Genders
Eligibility Criteria
You may qualify if you...
- Suitable for anthracycline-containing chemo-immunotherapy
- Patients with chronic lymphocytic leukaemia and newly diagnosed biopsy-proven diffuse large B-cell lymphoma (DLBCL)-type Richter's Syndrome
- ECOG performance status of 0, 1, 2, or 3
- Age 16 years and over
- Signed written informed consent before any study-specific procedures
You will not qualify if you...
- Prior therapy with CHOP or any anthracycline-containing treatment before randomisation
- Ibrutinib-exposed patients diagnosed with RS within four weeks of last ibrutinib dose
- Previous exposure to acalabrutinib
- Known central nervous system involvement of CLL or DLBCL
- Any other active malignancy requiring treatment (except certain skin and cervical cancers)
- Chronic or ongoing active infections needing systemic treatment
- Positive hepatitis B surface antigen or certain hepatitis B antibody tests with active infection
- Known HIV infection
- Active bleeding conditions or history of bleeding disorders
- Use of warfarin or equivalent therapeutic anticoagulation
- Prolonged blood clotting times beyond twice the normal limit
- Major surgery within 30 days prior to randomisation or inadequate recovery
- Malabsorption syndrome or significant gastrointestinal dysfunction
- Clinically significant heart disease excluding stable atrial fibrillation
- Severe uncontrolled medical conditions including kidney, liver, blood, lung, neurological, or psychiatric diseases
- History of serious stroke or brain hemorrhage within 6 months
- Known or suspected allergy to study drugs
- Use of non-marketed or experimental drugs within 4 weeks prior to treatment
- Current participation in another interventional clinical study
- Inability to comply with study protocol due to psychological or substance issues
- Breastfeeding women or positive pregnancy test at screening
- Women and men unwilling to use highly effective contraception during and 12 months after study treatment completion
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Up to 6 cycles of 21 days each; acalabrutinib continuous thereafter where applicable
Participants receive up to 6 cycles of CHOP-R chemotherapy every 21 days, with or without acalabrutinib. Those in the experimental arm take acalabrutinib tablets at home during and after chemotherapy continuously until disease progression, unacceptable toxicity, or patient choice. Participants in Cohort 1 receive acalabrutinib monotherapy continuously until disease progression or other reasons. Participants in Cohort 2 receive CHOP-R plus acalabrutinib during 6 cycles, then continue acalabrutinib alone if responding.
6 visits (in-person) for chemotherapy cycles; additional visits for assessments at weeks 12 and 24 for Cohort 1
Follow-up
Duration - At least 2 years
Participants are followed up for disease status and survival for at least 2 years after treatment to assess long-term effectiveness.
Regular follow-up visits as scheduled by the medical team
Trial Site Locations
Total: 16 locations
1
Belfast City Hospital
Belfast, United Kingdom
Actively Recruiting
2
Royal Bournemouth Hospital
Bournemouth, United Kingdom
Actively Recruiting
3
University Hospital of Wales
Cardiff, United Kingdom
Actively Recruiting
4
Beatson West of Scotland Cancer Centre
Glasgow, United Kingdom
Actively Recruiting
5
St James's University Hospital
Leeds, United Kingdom
Actively Recruiting
6
Leicester Royal Infirmary
Leicester, United Kingdom
Actively Recruiting
7
King's College Hospital
London, United Kingdom
Actively Recruiting
8
St Bartholomew's Hospital
London, United Kingdom
Actively Recruiting
9
University College London Hospital
London, United Kingdom
Actively Recruiting
10
Christie Hospital
Manchester, United Kingdom
Actively Recruiting
11
Norfolk and Norwich University Hospital
Norwich, United Kingdom
Actively Recruiting
12
Nottingham City Hospital
Nottingham, United Kingdom
Actively Recruiting
13
Churchill Hospital
Oxford, United Kingdom
Actively Recruiting
14
Derriford Hospital
Plymouth, United Kingdom
Actively Recruiting
15
Royal Hallamshire Hospital
Sheffield, United Kingdom
Actively Recruiting
16
Southampton General Hospital
Southampton, United Kingdom
Actively Recruiting
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Research Team
J
Joseph Rogers, MSc
F
Francesca Yates, PhD
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
RANDOMIZED
Model
PARALLEL
Primary Purpose
TREATMENT
Number of Arms
4
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Published Research Related To This Trial
The STELLAR trial protocol: a prospective multicentre trial for Richter's syndrome consisting of a randomised trial investigation CHOP-R with or without acalabrutinib for newly diagnosed RS and a single-arm platform study for evaluation of novel agents in relapsed disease.
Niamh Appleby, Toby A Eyre, Maite Cabes...
https://pubmed.ncbi.nlm.nih.gov/31109313