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

Recruitment & Eligibility

Status: Ongoing

Sex: All

Target Recruitment: 84

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

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Progression free survival (PFS); Timepoint(s): Time from randomisation to the date of progression or death from any cause.

Secondary Outcome Measures

Name	Time	Method

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