A Phase II, Randomised Study of CHOP-R in Combination With Acalabrutinib Compared to CHOP-R in Patients With Newly Diagnosed Richter's Syndrome and a Platform for Initial Investigations Into Activity of Novel Treatments in Relapsed/Refractory and Newly Diagnosed Richter's Syndrome.

Who is this study for? Patients with newly diagnosed Richter's syndrome
Status: Recruiting
Location: See all (16) locations...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 2
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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.

• Patients with relapsed/refractory RS who received anthracycline based chemotherapy with anti-CD20 monoclonal antibody If fewer than the expected number of patients from the randomised component enter into Cohort 1, patients from outside STELLAR with relapsed/refractory RS following chemo-immunotherapy (anthracycline based chemotherapy with anti-CD20 monoclonal antibody) will be able to join this cohort if they meet the eligibility criteria. The Trials Office will alert sites by email if any slots are released for patients outside of STELLAR, these must be booked with the Trials Office prior to registration.

• 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.

• 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.

Locations
Other Locations
United Kingdom
Belfast City Hospital
RECRUITING
Belfast
Royal Bournemouth Hospital
RECRUITING
Bournemouth
University Hospital of Wales
RECRUITING
Cardiff
Beatson West of Scotland Cancer Centre
RECRUITING
Glasgow
St James's University Hospital
RECRUITING
Leeds
Leicester Royal Infirmary
RECRUITING
Leicester
King's College Hospital
RECRUITING
London
St Bartholomew's Hospital
RECRUITING
London
University College London Hospital
RECRUITING
London
Christie Hospital
RECRUITING
Manchester
Norfolk and Norwich University Hospital
RECRUITING
Norwich
Nottingham City Hospital
RECRUITING
Nottingham
Churchill Hospital
RECRUITING
Oxford
Derriford Hospital
RECRUITING
Plymouth
Royal Hallamshire Hospital
RECRUITING
Sheffield
Southampton General Hospital
RECRUITING
Southampton
Contact Information
Primary
Joseph Rogers, MSc
STELLAR@trials.bham.ac.uk
+44 (0)121 371 7867
Backup
Francesca Yates, PhD
STELLAR@trials.bham.ac.uk
+44 (0)121 371 7867
Time Frame
Start Date: 2019-07-23
Estimated Completion Date: 2027-05-31
Participants
Target number of participants: 105
Treatments
Active_comparator: Standard of Care Arm (CHOP-R)
Arm in the randomised trial. CHOP-R chemoimmunotherapy 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
Experimental: Experimental Arm (CHOP-R + Acalabrutinib)
Arm in the randomised trial. CHOP-R chemoimmunotherapy 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 will be taken on days 6-21, of each cycle - up to cycle 6. Acalabrutinib treatment will be continuous thereafter until disease progression toxicity, patient choice or death.
Experimental: Cohort 1 - Acalabrutinib Monotherapy - Platform Trial
Registration arm in platform study. 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.
Experimental: Cohort 2 - CHOP-R + Acalabrutinib - Platform Trial
Registration arm in platform study. CHOP-R chemoimmunotherapy 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 will be taken on days 6-21, of each cycle - up to cycle 6. Acalabrutinib treatment will be continuous thereafter until disease progression toxicity, patient choice or death.
Related Therapeutic Areas
Sponsors
Leads: University of Birmingham
Collaborators: Bloodwise, Acerta Pharma, LLC

This content was sourced from clinicaltrials.gov