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

Launched by UNIVERSITY COLLEGE, LONDON · Aug 16, 2019

Keywords

ClinConnect Summary

The RAINBOW study is a clinical trial exploring new treatment options for Waldenström's macroglobulinaemia (WM), a rare and slow-growing type of lymphoma. The trial compares two treatment approaches: one using a combination of the drugs rituximab and ibrutinib, which does not involve traditional chemotherapy, and the other using a combination of rituximab, cyclophosphamide, and dexamethasone, which is a standard treatment for WM. The goal is to see if the new approach (RI) leads to better treatment outcomes, longer-lasting responses, and fewer side effects for patients.

To participate, you must be at least 18 years old and have a confirmed diagnosis of WM that requires treatment. You should not have received previous treatment for WM, and there are specific health criteria to ensure your safety during the trial. If you qualify and choose to participate, you will receive treatment for up to six cycles, with regular check-ups to monitor your progress. The study is being conducted in NHS hospitals and aims to recruit 148 participants over nearly ten years. This trial could help improve the way WM is treated in the future.

Gender

ALL

Eligibility 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.