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 ID: 38923
Short Title: STELLAR
Trust Name: UHD,UHS
Recruitment Site: Royal Bournemouth Hospital,Southampton General Hospital
Disease Area: Haematology
Phase: II
Expected End Date: 31/05/2024
Postcode: SO16 6YD
BH15 2JB
Contact Name: Amanda Pattie
Contact Email: studysupport1and3.crnwessex@nihr.ac.uk
Active: Yes

Inclusion criteria, exclusion criteria and study summary

Inclusion criteria for the Randomised Trial -Suitable for anthracycline-containing chemo-immunotherapy. -Patients with CLL and newly diagnosed biopsy proven DLBCL-type RS. -ECOG performance status of 0, 1, 2 or 3. -Age 16 years and over. -Signed written informed consent prior to performing any study-specific procedures Inclusion criteria Cohort 1 (progressive RS following chemo-immunotherapy) -Patients with relapsed/refractory RS who received anthracycline based chemotherapy with anti-CD20 monoclonal antibody. -ECOG performance status of 0, 1, 2 or 3. -Age 16 years and over. -Signed written informed consent prior to performing any study-specific procedures Inclusion criteria Cohort 2 (anthracycline-naïve RS patients, diagnosed while on ibrutinib) -Ibrutinib-exposed CLL patients who have developed biopsy-proven DLBCL-type RS within four weeks of last dose of ibrutinib. -No previous anthracycline treatment and suitable for anthracycline-containing chemo-immunotherapy. -Patients with CLL and newly diagnosed biopsy proven DLBCL-type RS. -ECOG performance status of 0, 1, 2 or 3. -Age 16 years and over. -Signed written informed consent prior to performing any study-specific procedures

Exclusion criteria ALL -Known central nervous system (CNS) involvement of CLL or DLBCL. -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. -Chronic or ongoing active infectious disease -Positive serology for Hepatitis B (HBKnown human immunodeficiency virus (HIV) positive. -Patients with active bleeding or history of bleeding diathesis (e.g. haemophilia, von Willebrand disease). -Patients receiving therapeutic anticoagulation with warfarin or equivalent (e.g. phenoprocoumon). -Uncorrected prolonged prothrombin time (PT) or an activated partial thromboplastin time (APTT) > 2 x the upper limit of normal (ULN). -Major surgery within 30 days prior to randomisation and/or inadequate recovery from any prior major surgery, toxicity or complications. -Patients with malabsorption syndrome or medical conditions significantly affecting gastrointestinal function. -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. -Significant concurrent, uncontrolled severe medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease. -History of significant cerebrovascular disease in the 6 months prior to randomisation, including intracranial haemorrhage. -Known or suspected hypersensitivity to components of the investigational products -Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to proposed start of treatment -Current participation in any other interventional clinical study. -Patients known or suspected of not being able to comply with a study -Breast feeding women or women with a positive pregnancy test at screening. -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 -Prior therapy with CHOP or any anthracycline containing treatment at any time prior to randomisation. -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). -Previous acalabrutinib exposure. Additional exclusion criteria for Cohort 1 (progressive RS following chemo-immunotherapy) -Previous acalabrutinib exposure. Additional exclusion criteria for Cohort 2 (anthracycline-naïve RS patients, diagnosed while on ibrutinib) -Prior therapy with CHOP or any anthracycline containing treatment at any time prior to randomisation. -Previous acalabrutinib exposure.

The STELLAR trial will assess the effect of acalabrutinib taken in combination with CHOP-R compared to taking CHOP-R alone in patients with newly diagnosed Richter’s Syndrome (RS). It will also be a platform to test other new drugs that show potential for treating RS. Chronic lymphocytic Leukaemia (CLL) is the most common blood cancer in adults, usually in their 70s or older. In a few patients, CLL can transform from a slow-growing cancer into an aggressive lymphoma called Richter’s Syndrome. RS is very difficult to treat and patients have a short life-expectancy - usually a few months after diagnosis. Treatment for Richter’s Syndrome in the UK is CHOP (four chemotherapy drugs) plus rituximab (‘R’ - an antibody treatment). The CHOP-R treatment is given as a standard of care for RS but has limited benefit - it is often temporary to extend life. Richter’s Syndrome returns in most patients who then die from this disease. The STELLAR trial will investigate if a new drug called acalabrutinib, which is effective used by itself in patients with relapsed CLL and also some with Richter’s Syndrome, will improve outcomes for newly diagnosed patients with RS. Acalabrutinib blocks a protein in CLL which can stop the cancer growing. 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. CHOP-R is given in a hospital every three weeks up to 6 times. All participants will receive CHOP-R; half will also receive acalabrutinib. When treatment with CHOP-R ends the patients who had acalabrutinib can continue to take it; patients who had CHOP-R alone may have acalabrutinib if their Richter’s Syndrome returns after CHOP-R.

Study MapList of studies

Accessibility tools

Return to header