ClinicalTrials.gov record NCT04061512

Rituximab and Ibrutinib (RI) Versus Dexamethasone, Rituximab and Cyclophosphamide (DRC) as Initial Therapy for Waldenström's Macroglobulinaemia

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 17, 2026

Randomised Phase II/III Study of Rituximab and Ibrutinib (RI) Versus Dexamethasone, Rituximab and Cyclophosphamide (DRC) as Initial Therapy for Waldenström's Macroglobulinaemia

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.The registry record was last updated on May 10, 2024, about 2 years ago, so the status shown may be out of date. The study team or the registry can confirm.
Study typeInterventionalA study in which researchers assign participants to one or more interventions, such as a drug, procedure, device, behavioural programme or other approach, to measure their effects.
PhasePhase 2/3A study that tests whether a treatment works while continuing to check safety, in a larger group than a phase 2 study alone. It combines the aims of phase 2 and phase 3 in one protocol.
Age18 years old and older
SexAll
LocationUnited Kingdom
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This randomized phase 2/3 trial compares a chemotherapy-free combination of rituximab plus ibrutinib (RI) with dexamethasone, rituximab and cyclophosphamide (DRC) as initial treatment for Waldenström's Macroglobulinaemia. About 148 adults with untreated WM will be randomized 1:1. Randomised treatment lasts up to six cycles; RI patients may then receive up to five years of ibrutinib monotherapy. Patients are assessed during treatment, then every 3 months for five years after treatment discontinuation, with annual survival follow-up thereafter.

What it is studying. The study compares RI versus DRC as first-line treatment for WM, measuring response rate at week 24 and progression-free survival at 2 years, along with safety, overall survival, duration of response, time to next treatment, and quality of life.

What the researchers hope to learn. To determine the preliminary response rate of rituximab plus ibrutinib at week 24, compare progression-free survival at 2 years between RI and DRC, and assess safety/tolerability, overall response rates, duration of response, time to next treatment, overall survival, and quality of life (EQ-5D-5L).

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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.

Interventions being studied

Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.

Drug
  • Dexamethasone, cyclophosphamide, rituximab
  • Rituximab, ibrutinib

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • 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)

Exclusion criteria

  • 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.
  • Inability to swallow oral medication
  • Disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption (e.g. malabsorption syndrome, resection of the small bowel, poorly controlled inflammatory bowel disease)
  • Active systemic infection requiring treatment
  • Concomitant treatment with another investigational agent
  • Any life-threatening illness, medical condition, organ system dysfunction, need for profound anticoagulation, or bleeding disorder, which, in the investigator's opinion, could compromise the patient's safety, or put the study at risk
  • Unwilling or unable to take PCP prophylaxis (e.g. cotrimoxazole)
  • History of prior malignancy, with the exception of the following:
  • Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to screening and felt to be at low risk for recurrence by treating physician
  • Adequately treated non-melanomatous skin cancer or lentigo maligna melanoma, superficial bladder cancer, carcinoma in situ of the cervix or breast or localized Gleason score 6 prostate cancer without current evidence of disease.

Study description and what participation involves

The registry record has no detailed description beyond the summary above.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

If you join, you will be randomly assigned to one of two first‑line drug treatments: rituximab plus ibrutinib (chemotherapy‑free RI arm) or dexamethasone, rituximab and cyclophosphamide (DRC control). Randomised treatment lasts up to six cycles; response is assessed after three cycles and again at about 24 weeks, and people in the RI arm may continue ibrutinib monotherapy for up to five years. You will have regular clinic visits during treatment, complete quality-of-life questionnaires (EQ-5D-5L), have treatment responses and side effects recorded (safety is followed until 30 days after the last study drug), then be reviewed every three months for five years after stopping treatment and enter annual survival follow-up until the trial ends.

How the study is structured. This is an interventional, randomized (1:1), open-label phase 2/3 trial with two parallel treatment groups: the experimental RI arm (rituximab plus ibrutinib) and the control DRC arm (dexamethasone, rituximab, cyclophosphamide). Participants receive up to six cycles of the assigned randomised treatment; those in the RI arm may continue ibrutinib monotherapy for up to five years. Responses are checked after three cycles and at about 24 weeks, with regular visits during treatment and scheduled follow-up visits afterward.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • The listed sites are in United Kingdom. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on Waldenström macroglobulinemia

Clinical trials63 trials listed for Waldenström macroglobulinemiaEvery trial the registry lists for Waldenström macroglobulinemia, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in Waldenström macroglobulinemia researchLatest monthly update: September 2026. Includes: Upfront treatment outcomes. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Feb 3, 2020
Primary completion
March 2030 (estimated)
Study completion
March 2030 (estimated)
Target enrollment
148 participants (estimated)
Last updated on registry
May 10, 2024
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
University College, London
Collaborators
  • Janssen-Cilag Ltd.

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (25)

  • Royal United Hospital, BathRecruiting

    Bath · United Kingdom

    • Josephine Crowe
  • The Royal Bournemouth and Christchurch Hospitals NHS Foundation TrustRecruiting

    Bournemouth · United Kingdom

    • Helen McCarthy
  • East Kent Hospitals University NHS Foundation TrustRecruiting

    Canterbury · United Kingdom

    • Jindriska Lindsay
  • University Hospital of WalesRecruiting

    Cardiff · United Kingdom

    • Simona Gatto
  • Colchester HospitalRecruiting

    Colchester · United Kingdom

    • Gavin Campbell
  • Mid Yorkshire NHS TrustRecruiting

    Dewsbury · United Kingdom

    • Joanna Haughton
  • Royal Devon University HospitalRecruiting

    Exeter · United Kingdom

    • Paul Kerr
  • Medway Maritime HospitalRecruiting

    Gillingham · United Kingdom

    • Sudarshan Gurung
  • Castle Hill HospitalRecruiting

    Hull · United Kingdom

    • James Bailey
  • NHS LanarkshireRecruiting

    Lanark · United Kingdom

    • Iain Singer
    • Iain Singer

Terms used on this page · explanations by MedicalUpdates.ai

phase 2
A study that tests whether a treatment has the intended effect and continues to check safety, usually in a larger group than phase 1.
experimental arm
One of the groups in a study. Each arm receives a particular intervention, comparator or no intervention, so the groups can be compared.
control arm
The group the study treatment is compared with. It may receive a placebo, an existing treatment (active comparator), a sham procedure, or no intervention.
randomised
Participants are assigned to the study groups by chance, like a coin toss, rather than chosen by the doctor or the participant. This is done so the groups are comparable.
1:1
How many participants go to each group. In a 2:1 ratio, two are assigned to the first group for every one assigned to the second.
follow up
The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
Previously untreated
Has not previously received the treatment, or the type of treatment, that the study is about.
ECOG
A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
Life expectancy
Some studies require that, in the investigator's judgement, a participant is likely to live long enough to complete the study period. It is a study requirement, not a prediction about any individual.
Written informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
women of childbearing potential
Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
Prior therapy
Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
QTcF
A recording of the heart's electrical activity. QTc is one measurement from it; some drugs are avoided if it is prolonged.
creatinine clearance
A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
Concomitant treatment
Other medicines a participant takes during the study. Some must be reported; some are restricted.
investigational agent
A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
prior to screening
The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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