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Comparing two treatment approaches for Waldenström's macroglobulinaemia

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

Phase2; Phase3 Interventional University College, London · NCT04061512

This study is testing a new treatment without chemotherapy for people with Waldenström's macroglobulinaemia to see if it works better and is easier on the body than the standard treatment.

Quick facts

PhasePhase2; Phase3
Study typeInterventional
Enrollment148 (estimated)
Ages18 Years and up
SexAll
SponsorUniversity College, London Academic / other
Drugs / interventionschemotherapy, rituximab, Ibrutinib, cyclophosphamide
Locations25 sites (Bath and 24 other locations)
Trial IDNCT04061512 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the effectiveness of a chemotherapy-free treatment regimen using Ibrutinib and Rituximab against the standard treatment of Dexamethasone, Rituximab, and Cyclophosphamide for patients with Waldenström's macroglobulinaemia. The study aims to improve patient outcomes by enhancing response rates and reducing treatment-related toxicity. Participants will be monitored for their response to the treatments, with a focus on durability and quality of life improvements. The trial includes both Phase 2 and Phase 3 assessments to ensure comprehensive evaluation of the new treatment approach.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older with a confirmed diagnosis of Waldenström's macroglobulinaemia who have not received prior chemotherapy.

Not a fit: Patients who have previously undergone treatment for Waldenström's macroglobulinaemia may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could provide a more effective and less toxic treatment option for patients with Waldenström's macroglobulinaemia.

How similar studies have performed: Other studies have shown promise with similar chemotherapy-free approaches in treating lymphomas, suggesting potential for success in this trial.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. Patients ≥ 18 years
2. Confirmed diagnosis of WM (according to consensus panel / WHO criteria) with measurable IgM paraprotein
3. 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
4. No previous chemotherapy (prior plasma exchange and steroids are permissible)
5. Eastern Cooperative Oncology Group (ECOG) performance status grade 0 - 2
6. Life expectancy of greater than 6 months
7. Written informed consent
8. Willing to comply with the contraceptive requirements of the trial
9. Negative serum or urine pregnancy test for women of childbearing potential (WOCBP)

Exclusion Criteria:

1. Prior therapy for WM
2. Lymphoplasmacytic lymphoma with no detectable serum IgM paraprotein
3. CNS involvement with WM
4. Autoimmune cytopenias
5. Major surgery within 4 weeks prior to randomisation
6. 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
7. History of stroke or intracranial haemorrhage within 6 months prior to randomisation
8. Requires anticoagulation with warfarin or equivalent vitamin K antagonists (direct oral anticoagulants (DOACs) allowed)
9. History of severe bleeding disorders considered not to be disease related (Haemophilia A, B or von Willebrand's disease)
10. Requires ongoing treatment with a strong CYP3A inhibitor or inducer
11. 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
12. 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"
13. Renal failure (creatinine clearance \<30 ml/min as estimated by the Cockroft-Gault equation)
14. Patients with chronic liver disease with hepatic impairment Child-Pugh class B or C
15. Known history of anaphylaxis following exposure to rat or mouse derived CDR-grafted humanised monoclonal antibodies.
16. Inability to swallow oral medication
17. 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)
18. Active systemic infection requiring treatment
19. Concomitant treatment with another investigational agent
20. 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
21. Unwilling or unable to take PCP prophylaxis (e.g. cotrimoxazole)
22. 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.

Where this trial is running

Bath and 24 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
Conditions Waldenstrom Macroglobulinemia
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.