Trial Outcomes & Findings for Ibrutinib and Ixazomib Citrate in Treating Newly Diagnosed, Relapsed or Refractory Waldenstrom Macroglobulinemia (NCT NCT03506373)

Last Updated: 2026-02-17

Results Overview

Complete response rate to be defined as an objective status of CR at any time, where confirmation of the complete response status is required on two consecutive evaluations with a second immunofixation before calling the patient a CR. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Categorized by Response Assessment Criteria as specified in Appendix III of the protocol.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

21 participants

Primary outcome timeframe

4 years

Results posted on

2026-02-17

Participant Flow

Participant milestones

Participant milestones
Measure	Treatment (Ixazomib Citrate, Ibrutinib) Patients receive ixazomib citrate 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.\> \> Ibrutinib: Given PO\> \> Ixazomib Citrate: Given PO\> \> Laboratory Biomarker Analysis: Correlative studies\> \> Pharmacodynamic Study: Correlative studies\> \> Pharmacokinetic Study: Correlative studies
Overall Study STARTED	21
Overall Study COMPLETED	5
Overall Study NOT COMPLETED	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Treatment (Ixazomib Citrate, Ibrutinib) Patients receive ixazomib citrate 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.\> \> Ibrutinib: Given PO\> \> Ixazomib Citrate: Given PO\> \> Laboratory Biomarker Analysis: Correlative studies\> \> Pharmacodynamic Study: Correlative studies\> \> Pharmacokinetic Study: Correlative studies
Overall Study Adverse Event	6
Overall Study Withdrawal by Subject	2
Overall Study Disease progression	5
Overall Study Other	3

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Treatment (Ixazomib Citrate, Ibrutinib) n=21 Participants Patients receive ixazomib citrate 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.\> \> Ibrutinib: Given PO\> \> Ixazomib Citrate: Given PO\> \> Laboratory Biomarker Analysis: Correlative studies\> \> Pharmacodynamic Study: Correlative studies\> \> Pharmacokinetic Study: Correlative studies
Age, Continuous	69 years STANDARD_DEVIATION 7.16 • n=25 Participants
Sex: Female, Male Female	6 Participants n=25 Participants
Sex: Female, Male Male	15 Participants n=25 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=25 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants n=25 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=25 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=25 Participants
Race (NIH/OMB) Asian	0 Participants n=25 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=25 Participants
Race (NIH/OMB) Black or African American	0 Participants n=25 Participants
Race (NIH/OMB) White	21 Participants n=25 Participants
Race (NIH/OMB) More than one race	0 Participants n=25 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=25 Participants
Region of Enrollment United States	21 participants n=25 Participants
ECOG Performance Status 0	12 Participants n=25 Participants
ECOG Performance Status 1	9 Participants n=25 Participants

PRIMARY outcome

Timeframe: 4 years

Outcome measures

Outcome measures
Measure	Treatment (Ixazomib Citrate, Ibrutinib) n=21 Participants Patients receive ixazomib citrate 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. \> \> Ibrutinib: Given PO \> \> Ixazomib Citrate: Given PO \> \> Laboratory Biomarker Analysis: Correlative studies \> \> Pharmacodynamic Study: Correlative studies \> \> Pharmacokinetic Study: Correlative studies
Complete Response Rate (CR)	0 percentage of participants

SECONDARY outcome

Timeframe: Up to 5 years

Overall response rate will be estimated by the total number of patients who achieve a CR, very good partial response (VGPR), or partial response (PR) divided by the total number of evaluable patients. All evaluable patients will be used for this analysis. Exact binomial 95% confidence intervals for the true overall response rate will be calculated. Response is categorized by Response Assessment Criteria as specified in Appendix III of the protocol.

Outcome measures

Outcome measures
Measure	Treatment (Ixazomib Citrate, Ibrutinib) n=21 Participants Patients receive ixazomib citrate 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. \> \> Ibrutinib: Given PO \> \> Ixazomib Citrate: Given PO \> \> Laboratory Biomarker Analysis: Correlative studies \> \> Pharmacodynamic Study: Correlative studies \> \> Pharmacokinetic Study: Correlative studies
Overall Response Rate	76.0 percentage of participants Interval 52.83 to 91.78

SECONDARY outcome

Timeframe: From study registration to the earliest date of documentation of disease progression, assessed up to 5 years

The median time to progression will be estimated using the method of Kaplan-Meier. Categorized by Response Assessment Criteria as specified in Appendix III of the protocol.

Outcome measures

Outcome measures
Measure	Treatment (Ixazomib Citrate, Ibrutinib) n=21 Participants Patients receive ixazomib citrate 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. \> \> Ibrutinib: Given PO \> \> Ixazomib Citrate: Given PO \> \> Laboratory Biomarker Analysis: Correlative studies \> \> Pharmacodynamic Study: Correlative studies \> \> Pharmacokinetic Study: Correlative studies
Progression-free Survival	22.9 months Interval 17.2 to The upper limit of the CI is not estimable due to a low number of events

SECONDARY outcome

Timeframe: Up to 5 years

Defined as the time from study enrollment until death due to any cause. The median overall survival will be estimated using the method of Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Treatment (Ixazomib Citrate, Ibrutinib) n=21 Participants Patients receive ixazomib citrate 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. \> \> Ibrutinib: Given PO \> \> Ixazomib Citrate: Given PO \> \> Laboratory Biomarker Analysis: Correlative studies \> \> Pharmacodynamic Study: Correlative studies \> \> Pharmacokinetic Study: Correlative studies
Overall Survival	NA months The median, upper limit and lower limit of the CI is not estimable due to a low number of events

SECONDARY outcome

Timeframe: Up to 5 years

The maximum grade for each type of AE will be recorded for each patient, and frequency tables will be reviewed to determine patterns. Additionally, the relationship of the AE(s) to the study treatment will be taken into consideration.

Outcome measures

Outcome measures
Measure	Treatment (Ixazomib Citrate, Ibrutinib) n=21 Participants Patients receive ixazomib citrate 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. \> \> Ibrutinib: Given PO \> \> Ixazomib Citrate: Given PO \> \> Laboratory Biomarker Analysis: Correlative studies \> \> Pharmacodynamic Study: Correlative studies \> \> Pharmacokinetic Study: Correlative studies
Number of Patients Experiencing Grade 3+ Adverse Effects (AE) Graded According to Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.0	13 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 5 years

15 protein/genes associated with BTK-signaling will be assessed and their levels from baseline samples will be compared with levels from samples during treatment. Changes over time will be evaluated using paired sample approaches (Wilcoxon signed rank test). Baseline levels will be correlated with response (responder versus \[vs.\] non-responder) using Wilcoxon rank sum tests.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 5 years

Blood samples \& bone marrow aspirate to be taken from participants. The study will explore biologic effects of ibrutinib and ixazomib on microenvironment in WM and correlate with response to treatment. Immunophenotyping of tumor infiltrating lymphocytes (TILs) using the Multi-Omyx TILs platform. This will identify 17 different types of TILs from BM samples collected at baseline and then after one cycle of treatment. This data is represented as % and actual cell counts. Next, identification of 4 types of T-cells from the blood. This will be done from peripheral blood samples collected at Baseline and then after one cycle of treatment with ixazomib + ibrutinib (Ixa+Ibr). Next, BTK receptor occupancy: This is a competitive-binding assay essentially and will be performed in CD19+/CD138+ WM cells collected at baseline and then after one cycle of treatment with Ixa+Ibr. Readout is % occupancy. Values to be correlated with response (responder vs. non-responder) using Wilcoxon rank sum tests.

Outcome measures

Outcome data not reported

Adverse Events

Treatment (Ixazomib Citrate, Ibrutinib)

Serious events: 5 serious events

Other events: 21 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Treatment (Ixazomib Citrate, Ibrutinib) n=21 participants at risk Pharmacokinetic Study: Correlative studies
Cardiac disorders Chest pain - cardiac	4.8% 1/21 • Number of events 1 • 5 years
Cardiac disorders Heart failure	4.8% 1/21 • Number of events 1 • 5 years
Gastrointestinal disorders Abdominal pain	4.8% 1/21 • Number of events 1 • 5 years
Gastrointestinal disorders Small intestinal obstruction	4.8% 1/21 • Number of events 1 • 5 years
General disorders Edema limbs	4.8% 1/21 • Number of events 1 • 5 years
General disorders Fever	4.8% 1/21 • Number of events 1 • 5 years
Infections and infestations Lung infection	9.5% 2/21 • Number of events 2 • 5 years
Metabolism and nutrition disorders Hyponatremia	4.8% 1/21 • Number of events 1 • 5 years
Musculoskeletal and connective tissue disorders Generalized muscle weakness	4.8% 1/21 • Number of events 1 • 5 years
Nervous system disorders Syncope	4.8% 1/21 • Number of events 1 • 5 years
Psychiatric disorders Confusion	4.8% 1/21 • Number of events 1 • 5 years
Renal and urinary disorders Hematuria	4.8% 1/21 • Number of events 1 • 5 years
Respiratory, thoracic and mediastinal disorders Hypoxia	4.8% 1/21 • Number of events 1 • 5 years

Other adverse events

Other adverse events
Measure	Treatment (Ixazomib Citrate, Ibrutinib) n=21 participants at risk Pharmacokinetic Study: Correlative studies
Musculoskeletal and connective tissue disorders Bone pain	4.8% 1/21 • Number of events 1 • 5 years
Musculoskeletal and connective tissue disorders Joint effusion	4.8% 1/21 • Number of events 1 • 5 years
Musculoskeletal and connective tissue disorders Pain in extremity	4.8% 1/21 • Number of events 2 • 5 years
Nervous system disorders Headache	4.8% 1/21 • Number of events 1 • 5 years
Nervous system disorders Peripheral motor neuropathy	38.1% 8/21 • Number of events 95 • 5 years
Nervous system disorders Peripheral sensory neuropathy	42.9% 9/21 • Number of events 109 • 5 years
Psychiatric disorders Confusion	4.8% 1/21 • Number of events 1 • 5 years
Respiratory, thoracic and mediastinal disorders Aspiration	4.8% 1/21 • Number of events 1 • 5 years
Respiratory, thoracic and mediastinal disorders Dyspnea	4.8% 1/21 • Number of events 1 • 5 years
Respiratory, thoracic and mediastinal disorders Hypoxia	9.5% 2/21 • Number of events 2 • 5 years
Vascular disorders Hypertension	9.5% 2/21 • Number of events 11 • 5 years
Investigations Platelet count decreased	52.4% 11/21 • Number of events 44 • 5 years
Investigations White blood cell decreased	4.8% 1/21 • Number of events 2 • 5 years
Metabolism and nutrition disorders Hypoalbuminemia	4.8% 1/21 • Number of events 1 • 5 years
Musculoskeletal and connective tissue disorders Arthralgia	4.8% 1/21 • Number of events 1 • 5 years
Blood and lymphatic system disorders Anemia	81.0% 17/21 • Number of events 149 • 5 years
Blood and lymphatic system disorders Leukocytosis	4.8% 1/21 • Number of events 1 • 5 years
Gastrointestinal disorders Diarrhea	28.6% 6/21 • Number of events 43 • 5 years
Gastrointestinal disorders Nausea	66.7% 14/21 • Number of events 58 • 5 years
Gastrointestinal disorders Vomiting	47.6% 10/21 • Number of events 21 • 5 years
General disorders Edema limbs	4.8% 1/21 • Number of events 2 • 5 years
General disorders Fatigue	76.2% 16/21 • Number of events 138 • 5 years
Immune system disorders Allergic reaction	4.8% 1/21 • Number of events 3 • 5 years
Infections and infestations Upper respiratory infection	4.8% 1/21 • Number of events 1 • 5 years
Investigations Lymphocyte count decreased	4.8% 1/21 • Number of events 1 • 5 years
Investigations Neutrophil count decreased	14.3% 3/21 • Number of events 4 • 5 years

Additional Information

Asher Chanan-Khan, MD

Mayo Clinic Jacksonville

Phone: 904-953-2708

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place