Rituximab and Ibrutinib (RI) Versus Dexamethasone, Rituximab and Cyclophosphamide (DRC) as Initial Therapy for Waldenström's Macroglobulinaemia
RAINBOW
Randomised Phase II/III Study of Rituximab and Ibrutinib (RI) Versus Dexamethasone, Rituximab and Cyclophosphamide (DRC) as Initial Therapy for Waldenström's Macroglobulinaemia
1 other identifier
interventional
148
1 country
25
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Feb 2020
Longer than P75 for phase_2
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 1, 2019
CompletedFirst Posted
Study publicly available on registry
August 19, 2019
CompletedStudy Start
First participant enrolled
February 3, 2020
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2030
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2030
May 10, 2024
May 1, 2024
10.1 years
July 1, 2019
May 9, 2024
Conditions
Outcome Measures
Primary Outcomes (2)
Percentage of patients achieving a preliminary efficacy (response) of the 'chemotherapy free' combination of rituximab and ibrutinib (RI) as primary therapy for WM.
Overall response rate at week 24
Progression free survival (PFS) analysis of rituximab/ibrutinib (RI) when compared to dexamethasone/rituximab/cyclophosphamide (DRC) at 2 years after the last randomisation
2 years after the last randomisation
Secondary Outcomes (6)
Safety and tolerability of RI compared to DRC assessed by the frequency of serious and non-serious adverse events according to CTCAE v5.0
until 30 calendar days post last IMP administration
Overall response rate (defined as complete response [CR], very good partial response [VGPR], partial response [PR] and minor response [MR]) of RI compared to DRC (at end of randomised treatment and best response over any time point)
through study completion, an average of 2 years.
Time to next treatment
through study completion, an average of 2 years.
Duration of response of RI compared to DRC
through study completion, an average of 2 years.
Overall survival (OS) of patients treated with RI compared to DRC
date of randomisation until the date of death (of any cause)
- +1 more secondary outcomes
Study Arms (2)
DRC Arm
ACTIVE COMPARATORThe DRC arm (chemotherapy) is the control arm and consists of rituximab, cyclophosphamide and dexamethasone. It is widely recommended by international consensus as appropriate treatment for first-line therapy for WM.
RI Arm
EXPERIMENTALThe RI arm (chemotherapy free) arm will be using the drug ibrutinib, which in combination with rituximab (RI) will be the experimental arm.
Interventions
DRC Arm (chemotherapy) consists of dexamethasone, cyclophosphamide and rituximab treatment
RI Arm (chemotherapy free) consists of rituximab and ibrutinib treatment
Eligibility Criteria
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
- +19 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- University College, Londonlead
- Janssen-Cilag Ltd.collaborator
Study Sites (25)
Royal United Hospital, Bath
Bath, United Kingdom
The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
Bournemouth, United Kingdom
East Kent Hospitals University NHS Foundation Trust
Canterbury, United Kingdom
University Hospital of Wales
Cardiff, United Kingdom
Colchester Hospital
Colchester, United Kingdom
Mid Yorkshire NHS Trust
Dewsbury, United Kingdom
Royal Devon University Hospital
Exeter, United Kingdom
Medway Maritime Hospital
Gillingham, United Kingdom
Castle Hill Hospital
Hull, United Kingdom
NHS Lanarkshire
Lanark, United Kingdom
St James's University Hospital
Leeds, United Kingdom
Leicester Royal Infirmary
Leicester, United Kingdom
Barking, Havering and Redbridge University Hospitals NHS Trust
London, United Kingdom
Barts Health NHS Trust
London, United Kingdom
King's College Hospital
London, United Kingdom
Northwick Park Hospital
London, United Kingdom
University College London Hospitals NHS Foundation Trust
London, United Kingdom
Christie NHS Foundation Trust
Manchester, United Kingdom
Norfolk and Norwich Hospital
Norwich, United Kingdom
Oxford University Hospital
Oxford, United Kingdom
University Hospitals Plymouth NHS Trust
Plymouth, United Kingdom
Salisbury NHS Foundation Trust
Salisbury, United Kingdom
Torbay & Newton Abbot Hospital
Torquay, United Kingdom
Royal Cornwall Hospital
Truro, United Kingdom
Hampshire Hospitals NHS Foundation Trust
Winchester, United Kingdom
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 1, 2019
First Posted
August 19, 2019
Study Start
February 3, 2020
Primary Completion (Estimated)
March 1, 2030
Study Completion (Estimated)
March 1, 2030
Last Updated
May 10, 2024
Record last verified: 2024-05
Data Sharing
- IPD Sharing
- Will not share