Rituximab and Ibrutinib (RI) Versus Dexamethasone, Rituximab and Cyclophosphamide (DRC) as Initial Therapy for Waldenström's Macroglobulinaemia
Recruiting now · Phase 2/Phase 3
Conditions studied: Waldenstrom Macroglobulinemia
In brief
Waldenström's macroglobulinaemia (WM) is a rare type of slow growing lymphoma. It develops when white blood cells grow abnormally. Typically a disease of the elderly, the median age of presentation is \>70 years and the current treatment for WM is unsatisfactory, with incomplete responses and inevitable recurrence. Therefore there is a need to find alternative treatments that are more effective, leading to lasting responses and improved quality of life. The RAINBOW study is a phase 2-3 trial assessing 'chemotherapy free' treatment as primary therapy for WM which can potentially improve response outcome, durability and importantly, reduce toxicity for WM patients. This approach will be done using the drug Ibrutinib, which in combination with rituximab (RI) will be the experimental arm. As there is no agreed standard on first-line therapy for WM, the control arm is the current treatment based on the most recently published clinical trial results. The control arm consists of rituximab, cyclophosphamide and dexamethasone (DCR), and is widely recommended by international consensus as appropriate treatment for first-line therapy for WM. In this study, 148 adults (aged ≥ 18 years) with treatment naïve WM will be randomised on a 1:1 ratio to either the treatment or control arm. Randomised treatment lasts for a maximum of 6 cycles and response will be assessed following 3 cycles of treatment and completion of randomised treatment at approximately 24 weeks after commencing treatment. RI patients may then have up to 5 years of Ibrutinib monotherapy. Patients will be seen regularly during treatment and then every 3 months for 5 years after treatment discontinuation. Patients will enter annual follow up for survival until the end of trial (including progressed patients). The study will be conducted at NHS hospitals and is expected to last 9 years and 6 months.
Key facts
- Study ID
- NCT04061512
- Run by
- University College, London
- People needed
- 148
- Starts
- 2020-02-03
- Expected to finish
- 2030-03-01
- Last updated by the study team
- 2024-05-10
Who can join
Age: 18 and older. Sex: any. Healthy volunteers: not accepted.
You may qualify if…
- Patients ≥ 18 years
- Confirmed diagnosis of WM (according to consensus panel / WHO criteria) with measurable IgM paraprotein
- Previously untreated disease at any stage requiring therapy at the discretion of the treating physician. Suggested criteria for initiating treatment include:
- haematological suppression to Hb <10g/dl, or neutrophils <1.5x109/l or platelets <150x109/l
- clinical evidence of hyperviscosity
- bulky lymphadenopathy and/or bulky splenomegaly
- presence of B symptoms
- No previous chemotherapy (prior plasma exchange and steroids are permissible)
- Eastern Cooperative Oncology Group (ECOG) performance status grade 0 - 2
- Life expectancy of greater than 6 months
- Written informed consent
- Willing to comply with the contraceptive requirements of the trial
- Negative serum or urine pregnancy test for women of childbearing potential (WOCBP)
You may not qualify if…
- Prior therapy for WM
- Lymphoplasmacytic lymphoma with no detectable serum IgM paraprotein
- CNS involvement with WM
- Autoimmune cytopenias
- Major surgery within 4 weeks prior to randomisation
- Clinically significant cardiac disease including the following:
- Myocardial infarction within 6 months prior to randomisation
- Unstable angina within 3 months prior to randomisation
- New York Heart Association class III or IV congestive heart failure
- History of clinically significant arrhythmias (e.g. sustained ventricular tachycardia, ventricular fibrillation, torsades de pointes)
- QTcF > 480 msecs based on Fredericia's formula or Bazette's formula
- History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place
- Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood pressure measurements showing systolic blood pressure > 170 mmHg and diastolic blood pressure > 105 mm Hg
- Cardiac event within 6 months of screening (e.g. coronary artery stent) requiring dual antiplatelet treatment
- History of stroke or intracranial haemorrhage within 6 months prior to randomisation
- Requires anticoagulation with warfarin or equivalent vitamin K antagonists (direct oral anticoagulants (DOACs) allowed)
- History of severe bleeding disorders considered not to be disease related (Haemophilia A, B or von Willebrand's disease)
- Requires ongoing treatment with a strong CYP3A inhibitor or inducer
- Known infection with HIV, or serologic status reflecting active hepatitis B or C infection as follows:
- Presence of hepatitis B surface antigen (HBsAg). In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the patient will be excluded
- Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV antibody are eligible if HCV RNA is undetectable
- Women who are pregnant or breastfeeding or males expecting to conceive or father children at any point from the start of treatment until the end of the "at risk period"
- Renal failure (creatinine clearance <30 ml/min as estimated by the Cockroft-Gault equation)
- Patients with chronic liver disease with hepatic impairment Child-Pugh class B or C
- Known history of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanised monoclonal antibodies.
Where it is running
- Royal United Hospital, Bath — Bath, United Kingdom (enrolling)
- The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust — Bournemouth, United Kingdom (enrolling)
- East Kent Hospitals University NHS Foundation Trust — Canterbury, United Kingdom (enrolling)
- University Hospital of Wales — Cardiff, United Kingdom (enrolling)
- Colchester Hospital — Colchester, United Kingdom (enrolling)
- Mid Yorkshire NHS Trust — Dewsbury, United Kingdom (enrolling)
- Royal Devon University Hospital — Exeter, United Kingdom (enrolling)
- Medway Maritime Hospital — Gillingham, United Kingdom (enrolling)
- Castle Hill Hospital — Hull, United Kingdom (enrolling)
- NHS Lanarkshire — Lanark, United Kingdom (enrolling)
- St James's University Hospital — Leeds, United Kingdom (enrolling)
- Leicester Royal Infirmary — Leicester, United Kingdom (enrolling)
- Barking, Havering and Redbridge University Hospitals NHS Trust — London, United Kingdom (enrolling)
- Barts Health NHS Trust — London, United Kingdom (enrolling)
- King's College Hospital — London, United Kingdom (enrolling)
- Northwick Park Hospital — London, United Kingdom (enrolling)
- University College London Hospitals NHS Foundation Trust — London, United Kingdom (enrolling)
- Christie NHS Foundation Trust — Manchester, United Kingdom (enrolling)
- Norfolk and Norwich Hospital — Norwich, United Kingdom (enrolling)
- Oxford University Hospital — Oxford, United Kingdom (enrolling)
- University Hospitals Plymouth NHS Trust — Plymouth, United Kingdom (enrolling)
- Salisbury NHS Foundation Trust — Salisbury, United Kingdom (enrolling)
- Torbay & Newton Abbot Hospital — Torquay, United Kingdom (enrolling)
- Royal Cornwall Hospital — Truro, United Kingdom (enrolling)
- Hampshire Hospitals NHS Foundation Trust — Winchester, United Kingdom (enrolling)
Full record on ClinicalTrials.gov
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