A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study of Ibrutinib or Placebo in Combination With Rituximab in Subjects with Previously Treated Waldenstrom’s Macroglobulinemia

Phase 1

• Conditions: Relapsed or refractory Waldenstrom’s Macroglobulinemia; MedDRA version: 16.1Level: PTClassification code 10047804Term: Waldenstrom's macroglobulinaemia recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-005478-22-IT
• Lead Sponsor: Pharmacyclics, Incorporated

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-04-29
• Last Update Posted: 21 December 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 181

Inclusion Criteria

For the Randomized Study (Arm A and Arm B):

- Previously treated for Waldenstrom’s macroglobulinemia and have either documented disease progression or had no response (stable disease) to the most recent treatment regimen.
- Centrally confirmed clinicopathological diagnosis of WM in accordance with the consensus panel of the Second International Workshop on WM (Owen 2003).
- Measurable disease defined as serum monoclonal IgM >0.5 g/dL.
- Symptomatic disease meeting at least 1 of the recommendations from the Second International Workshop on Waldenström Macroglobulinemia for requiring treatment (Kyle 2003).
- Adequate hematologic function.
- Adequate hepatic and renal function.
- PT/INR =1.5 x ULN and PTT (aPTT) =1.5 x ULN.
- Eastern Cooperative Oncology Group (ECOG) performance status of =2. Ethical/Other

For the Open-label Substudy Treatment Arm C:
To be enrolled in the substudy, each potential subject must meet all of the inclusion criteria defined in Protocol Section 4.1.1 (Arm A & Arm B). IN ADDITION, the following criterion must be met:
1. Disease that is refractory to the last prior rituximab-containing therapy defined as either
• Relapse after the last rituximab-containing therapy <12 months since last dose of rituximab,
OR
• Failure to achieve at least a MR after the last rituximab-containing therapy.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 90
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion Criteria

- Known involvement of the central nervous system by WM.
- Disease that is refractory to the last prior rituximab-containing therapy defined as either
• Relapse after the last rituximab-containing therapy <12 months since last dose of
rituximab,
OR
• Failure to achieve at least a MR after the last rituximab-containing therapy.
If the subject meets this exclusion criterion and therefore is excluded from the main randomized study, participation in the non randomized substudy (Arm C) may be considered (Section 4.2)
- Rituximab treatment within the last 12 months before the first dose of study drug.
- Known anaphylaxis or IgE-mediated hypersensitivity to murine proteins or to any component of rituximab.
- Prior exposure to ibrutinib or other BTK inhibitors.
- Received any WM-related therapy (eg, chemotherapy, immunotherapy, investigational drug) =30 days prior to first administration of study treatment.
- Known bleeding disorders (eg, von Willebrand’s disease) or hemophilia.
- History of stroke or intracranial hemorrhage within 12 months prior to enrollment.
- Known history of infection with human immunodeficiency virus (HIV).
- History of active or chronic infection with hepatitis C virus (HCV) or hepatitis B virus (HBV) .
- Any uncontrolled active systemic infection.
- Major surgery (as defined in Section 6.2.2) within 4 weeks of first dose of study drug.
- Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator’s opinion, could compromise the subject’s safety or put the study outcomes at undue risk.
- Significant screening electrocardiogram (ECG) abnormalities.
- Currently active, clinically significant cardiovascular disease.
- Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function.
- Concomitant use of warfarin or other Vitamin K antagonists.
- Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor.

The exclusion criteria for the substudy are identical to those of the main randomized study as described in Protocol Section 4.1.2, EXCEPT for criteria 2, 3, and 4, which are related to prior rituximab use and do not apply for the substudy Arm C.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified