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

NCT03506373 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: MC178B18-000580
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Refractory Waldenstrom Macroglobulinemia; Waldenstrom Macroglobulinemia; Recurrent Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Complete Response Rate (CR)

  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.

  4 years

Secondary Outcomes (4)

• Overall Response Rate

  Up to 5 years

• Progression-free Survival

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

• Overall Survival

  Up to 5 years

• Number of Patients Experiencing Grade 3+ Adverse Effects (AE) Graded According to Common Terminology Criteria for Adverse Events (CTCAE) Version (v.) 4.0

  Up to 5 years

Other Outcomes (2)

• BTK Signaling Proteins (Western Blot and Densitometric Quantification) and Gene Expression (Quantitative Real-time Polymerase Chain Reaction [PCR]) Examined in CD19/CD138+ Waldenstrom Macroglobulinemia (WM) Cells

  Up to 5 years

• Biologic Effects of Ibrutinib and Ixazomib Citrate on Microenvironment in WM

  Up to 5 years

Study Arms (1)

Treatment (ixazomib citrate, ibrutinib)

EXPERIMENTAL

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.

Drug: Ibrutinib; Drug: Ixazomib Citrate; Other: Laboratory Biomarker Analysis; Other: Pharmacodynamic Study; Other: Pharmacokinetic Study

Interventions

Ibrutinib DRUG

Given PO

Also known as: BTK Inhibitor PCI-32765, CRA-032765, Imbruvica, PCI-32765

Treatment (ixazomib citrate, ibrutinib)

Ixazomib Citrate DRUG

Given PO

Also known as: MLN-9708, MLN9708, Ninlaro

Treatment (ixazomib citrate, ibrutinib)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (ixazomib citrate, ibrutinib)

Pharmacodynamic Study OTHER

Correlative studies

Also known as: PHARMACODYNAMIC

Treatment (ixazomib citrate, ibrutinib)

Pharmacokinetic Study OTHER

Correlative studies

Also known as: PHARMACOKINETIC, PK Study

Treatment (ixazomib citrate, ibrutinib)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Provide written informed consent
• Willingness to provide mandatory blood specimens and bone marrow specimens for correlative research
• Willingness to return to enrolling institution for follow-up

You may not qualify if:

• 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
• Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption or tolerance of ixazomib or ibrutinib, including difficulty swallowing
• History of any other prior malignancy; (NOTE: Exception to this are adequately treated non-melanoma skin cancers, any in situ cancer, adequately treated stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for at least two years prior to study enrollment)
• Patient has \>= grade 2 peripheral neuropathy or grade 1 peripheral neuropathy with pain on clinical examination during the screening period
• Any of the following because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
• Pregnant women

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (2)

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

Location

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

ibrutinib; ixazomib; Pharmacogenomic Variants

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Polymorphism, Genetic; Genetic Variation; Genetic Phenomena

Results Point of Contact

• Title: Asher Chanan-Khan, MD
• Organization: Mayo Clinic Jacksonville

chanan-khan.asher@mayo.edu

904-953-2708

Study Officials

• Asher A. Chanan-Khan, M.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2018
• First Posted: April 24, 2018
• Study Start: August 14, 2018
• Primary Completion: February 6, 2023
• Study Completion: February 3, 2026
• Last Updated: May 5, 2026
• Results First Posted: September 18, 2025

Record last verified: 2026-02

Locations

US (2)