Status:
RECRUITING
Rituximab and Ibrutinib (RI) Versus Dexamethasone, Rituximab and Cyclophosphamide (DRC) as Initial Therapy for Waldenström's Macroglobulinaemia
Lead Sponsor:
University College, London
Collaborating Sponsors:
Janssen-Cilag Ltd.
Conditions:
Waldenstrom Macroglobulinemia
Eligibility:
All Genders
18+ years
Phase:
PHASE2
PHASE3
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 i...
Eligibility Criteria
Inclusion
- 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
- 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.
Key Trial Info
Start Date :
February 3 2020
Trial Type :
INTERVENTIONAL
Allocation :
ESTIMATED
End Date :
March 1 2030
Estimated Enrollment :
148 Patients enrolled
Trial Details
Trial ID
NCT04061512
Start Date
February 3 2020
End Date
March 1 2030
Last Update
May 10 2024
Active Locations (25)
Enter a location and click search to find clinical trials sorted by distance.
1
Royal United Hospital, Bath
Bath, United Kingdom
2
The Royal Bournemouth and Christchurch Hospitals NHS Foundation Trust
Bournemouth, United Kingdom
3
East Kent Hospitals University NHS Foundation Trust
Canterbury, United Kingdom
4
University Hospital of Wales
Cardiff, United Kingdom