Rituximab and Ibrutinib (RI) Versus Dexamethasone, Rituximab and Cyclophosphamide (DRC) as Initial Therapy for Waldenström's Macroglobulinaemia (RAINBOW)
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|ClinicalTrials.gov Identifier: NCT04061512|
Recruitment Status : Not yet recruiting
First Posted : August 19, 2019
Last Update Posted : August 19, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Waldenstrom Macroglobulinemia||Drug: Dexamethasone, cyclophosphamide, rituximab Drug: Rituximab, ibrutinib||Phase 2 Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||148 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Randomised Phase II/III Study of Rituximab and Ibrutinib (RI) Versus Dexamethasone, Rituximab and Cyclophosphamide (DRC) as Initial Therapy for Waldenström's Macroglobulinaemia|
|Estimated Study Start Date :||August 31, 2019|
|Estimated Primary Completion Date :||February 28, 2029|
|Estimated Study Completion Date :||February 28, 2029|
Active Comparator: DRC Arm
The 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.
Drug: Dexamethasone, cyclophosphamide, rituximab
DRC Arm (chemotherapy) consists of dexamethasone, cyclophosphamide and rituximab treatment
Experimental: RI Arm
The RI arm (chemotherapy free) arm will be using the drug ibrutinib, which in combination with rituximab (RI) will be the experimental arm.
Drug: Rituximab, ibrutinib
RI Arm (chemotherapy free) consists of rituximab and ibrutinib treatment
- Percentage of patients achieving a preliminary efficacy (response) of the 'chemotherapy free' combination of rituximab and ibrutinib (RI) as primary therapy for WM. [ Time Frame: 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 [ Time Frame: 2 years after the last randomisation ]
- Safety and tolerability of RI compared to DRC assessed by the frequency of serious and non-serious adverse events according to CTCAE v5.0 [ Time Frame: 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) [ Time Frame: through study completion, an average of 2 years. ]
- Time to next treatment [ Time Frame: through study completion, an average of 2 years. ]
- Duration of response of RI compared to DRC [ Time Frame: through study completion, an average of 2 years. ](responding patients only)
- Overall survival (OS) of patients treated with RI compared to DRC [ Time Frame: date of randomisation until the date of death (of any cause) ]
- Quality of Life:EQ-5D-5L questionnaire [ Time Frame: 1 year and 2 years after completion of randomised treatment against the baseline quality of life score ]Change in quality of life (QoL) responses in each arm assessed by EQ-5D-5L questionnaire
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04061512
|Contact: RAINBOW Trial Coordinator||0207 679 email@example.com|
|Contact: Richard Jennerfirstname.lastname@example.org|