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TERMINATEDPHASE2

Ibrutinib and Ixazomib Citrate in Treating Newly Diagnosed, Relapsed or Refractory Waldenstrom Macroglobulinemia

Phase II Study of Ibrutinib in Combination With Ixazomib in Patients With Waldenström Macroglobulinemia

NCT03506373•Mayo Clinic

Summary

This phase II trial studies the side effects of ibrutinib citrate when given with ixazomib, and determines how well they work in treating patients with Waldenstrom macroglobulinemia that is newly diagnosed, has come back (recurrent) or does not respond to treatment (refractory). Enzyme inhibitors, such as ibrutinib and ixazomib citrate, may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.

Detailed Description

PRIMARY OBJECTIVE: I. To determine the efficacy (as assessed by complete response \[CR\] rate) of the combination of ixazomib citrate (ixazomib) and ibrutinib in Waldenstrom macroglobulinemia (WM) patients. SECONDARY OBJECTIVES: I. To assess the overall response rate (ORR=partial response \[PR\] or better) in WM patients treated with ixazomib and ibrutinib. II. To assess the time to progression (TTP) in WM patients treated with ixazomib and ibrutinib. III. To further characterize the safety and toxicity of the combination of ibrutinib and ixazomib. IV. To assess the overall survival (OS) in WM patients treated with ixazomib and ibrutinib. CORRELATIVE RESEARCH OBJECTIVES: I. To determine the role of members of the BTK signalosome in achievement or lack thereof of response to ibrutinib and ixazomib. II. To explore biologic effects of ibrutinib and ixazomib on microenvironment in WM and correlate with response to treatment. OUTLINE: Patients receive ixazomib citrate orally (PO) on days 1, 8, and 15 and ibrutinib PO daily on days 1-28. Treatment repeats every 28 days for up to 24 cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for up to 2 years.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Histological confirmation of WM; patients may have newly diagnosed, relapsed, or refractory disease; (definition: newly diagnosed; patients previously untreated for WM, relapse; patients who have received prior treatment for WM and now have disease recurrence; refractory; patients who have received anti-WM therapy and are noted to have progressive disease while on therapy, or those patients who demonstrated disease progression within 6 months of the last anti-WM treatment); NOTE: Ibrutinib naïve patients are allowed; if previously treated with ibrutinib, subject must have reached a response of at least stable disease (SD) and cannot have progressed while on ibrutinib; if subject stopped taking ibrutinib for reasons other than progression, they cannot have progressed for at least 6 months post last dose of ibrutinib
•Presence of measurable disease as defined by: presence of immunoglobulin M (IgM) paraprotein, measurable lymphadenopathy on imaging studies and/or physical exam, and/or bone marrow infiltration \> 10%
•Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
•Absolute neutrophil count (ANC) \>= 1000/mm\^3 (obtained =\< 14 days prior to registration)
•Platelet count \>= 75,000/mm\^3 (obtained =\< 14 days prior to registration) (NOTE: platelet transfusions in order to help patients meet eligibility criteria are not allowed)
•Hemoglobin \>= 9.0 g/dL (obtained =\< 14 days prior to registration)
•Total bilirubin =\< 1.5 x upper limit of normal (ULN) unless due to Gilbert's syndrome, in which case the direct bilirubin must be =\< 1.5 x ULN (obtained =\< 14 days prior to registration)
•Aspartate transaminase (AST) and alanine aminotransferase (ALT) =\< 3 x ULN (obtained =\< 14 days prior to registration)
•Calculated creatinine clearance must be \>= 30 ml/min using the Cockcroft Gault formula (obtained =\< 14 days prior to registration)
•Negative pregnancy test done at screening and =\< 3 days (72 hours) prior to registration, for women of childbearing potential
+3 more criteria

Exclusion Criteria

•Failure to have fully recovered (i.e., =\< grade 1 toxicity) from the reversible effects of prior treatment for WM
•Major surgical procedure (including open biopsy, excluding central line intravenous (IV) and port-a-cath placement) within =\< 14 days prior to initiating study treatment, or anticipation of the need for major surgery during the course of the study treatment
•Radiotherapy =\< 14 days prior to registration; if the involved field is small, 7 days will be considered a sufficient interval between treatment and administration of the ixazomib
•Systemic treatment, =\< 14 days before registration, with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or St. John's wort
•Systemic anti-cancer therapy or participation in other clinical trials, including those with other investigational agents not included in this trial, =\< 28 days of registration and throughout the duration of active treatment in this trial
•Patients that have previously been treated with ixazomib, or participated in a study with ixazomib whether treated with ixazomib or not; prior bortezomib treatment is allowed as per: patients with prior exposure to bortezomib will be allowed if they do not have disease refractory to bortezomib)
•Central nervous system involvement (Bing-Neel syndrome)
•Infection requiring systemic antibiotic therapy or other serious infection =\< 7 days prior to registration
•Evidence of current uncontrolled cardiovascular conditions, including uncontrolled hypertension, serious cardiac arrhythmia requiring medication (other than adequately rate-controlled atrial fibrillation), symptomatic congestive heart failure, unstable angina, stroke/transient ischemic attack (TIA) within the past 6 months or myocardial infarction within the past 6 months
•Known allergy to any of the study medications, their analogues, or excipients in the various formulations of any agent
+11 more criteria

Locations (2)

Mayo Clinic in Florida

Jacksonville, Florida, United States

Mayo Clinic in Rochester

Rochester, Minnesota, United States

Key Dates

Start Date

August 14, 2018

Primary Completion Date

February 6, 2023

Completion Date

February 3, 2026

Last Updated

March 5, 2026

Enrollment

ACTUAL participants

Conditions

Recurrent Waldenstrom MacroglobulinemiaRefractory Waldenstrom MacroglobulinemiaWaldenstrom Macroglobulinemia

Interventions

Ibrutinib

DRUG

Ixazomib Citrate

DRUG

Laboratory Biomarker Analysis

OTHER

Pharmacodynamic Study

OTHER

Pharmacokinetic Study

OTHER

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: March 5, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Ibrutinib and Ixazomib Citrate in Treating Newly Diagnosed, Relapsed or Refractory Waldenstrom Macroglobulinemia

Inclusion Criteria

Exclusion Criteria

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