Ibrutinib and Ixazomib Citrate in Treating Participants With Relapsed or Refractory Waldenstrom Macroglobulinemia

Overview

  • Study type

    Interventional
  • Study phase

    II
  • Study IDs

  • Describes the nature of a clinical study. Types include:

    • Observational study — observes people and measures outcomes without affecting results.
    • Interventional study (clinical trial) — studies new tests, treatments, drugs, surgical procedures or devices.
    • Medical records research — uses historical information collected from medical records of large groups of people to study how diseases progress and which treatments and surgeries work best.
  • During the early phases (phases 1 and 2), researchers assess safety, side effects, optimal dosages and risks/benefits. In the later phase (phase 3), researchers study whether the treatment works better than the current standard therapy. They also compare the safety of the new treatment with that of current treatments. Phase 3 trials include large numbers of people to make sure that the result is valid. There are also less common very early (phase 0) and later (phase 4) phases. Phase 0 trials are small trials that help researchers decide if a new agent should be tested in a phase 1 trial. Phase 4 trials look at long-term safety and effectiveness, after a new treatment has been approved and is on the market.

  • Site IRB
    • Jacksonville, Florida: 18-000580
    • Rochester, Minnesota: 18-000580
    NCT ID: NCT03506373
    Sponsor Protocol Number: MC178B

About this study

This phase II trial studies the side effects of ibrutinib citrate when given with ixazomib, and determines how well they work in treating participants with Waldenstrom macroglobulinemia that has come back or does not respond to treatment. 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.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. If you need assistance understanding the eligibility criteria, please contact the study team.

See eligibility criteria

Inclusion Criteria:

  • Histological confirmation of WM for which the patient has received at least one prior treatment; patients may have relapsed or refractory disease;(definition: 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)
  • 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
  • Obtained ≤14 days prior to registration: absolute neutrophil count (ANC) ≥ 1000/mm³
  • Obtained ≤ 14 days prior to registration: Platelet count ≥75,000/mm3 (NOTE: platelet transfusions in order to help patients meet eligibility criteria are not allowed)
  • Obtained ≤ 14 days prior to registration: hemoglobin > 9.0 g/dL
  • Obtained ≤ 14 days prior to registration: total bilirubin ≤1.5 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
  • 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

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; (NOTE: prior ibrutinib treatment is allowed as per: patients with prior exposure to ibrutinib will be allowed if they do not have disease refractory to ibrutinib; patient receiving ibrutinib will be allowed on this trial if they have measurable disease and did not have disease progression while receiving ibrutinib; 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
    • Pregnant women
    • Nursing women
    • Men or women of child bearing potential (WCBP) who are unwilling to employ effective contraception; effective contraception would be defined as utilizing 2 simultaneous methods of contraception from the time of signing consent through 90 days after the last dose of the study drugs unless they agree to participate in true abstinence when this is in line with the preferred and usual lifestyle of the subject; (women of child bearing potential [WCBP]: a female who is sexually mature and who: [1] has not undergone a hysterectomy or bilateral oophorectomy; or [2] has not been naturally postmenopausal for at least 24 consecutive months [i.e., has had menses at any time in the preceding 24 consecutive months])
  • Evidence of any other serious medical condition (such as psychiatric illness, infectious diseases, physical or laboratory findings) that may interfere with the planned treatment, affect compliance or place the patient at high risk from treatment-related complications or potentially interfere with the completion of the treatment as per the protocol
  • Ongoing, active hepatitis B or C virus infection, or known human immunodeficiency virus (HIV) positive
  • Liver disease with Child-Pugh class B or C liver dysfunction
  • Current treatment with a combination of ibrutinib and strong CYP3A inhibitors

Participating Mayo Clinic locations

Study statuses change often. Please contact us for help.

Mayo Clinic Location Status Contact

Jacksonville, Fla.

Mayo Clinic principal investigator

Asher Chanan-Khan, M.B.B.S., M.D.

Open for enrollment

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015

Rochester, Minn.

Mayo Clinic principal investigator

Asher Chanan-Khan, M.B.B.S., M.D.

Contact us for the latest status

Contact information:

Cancer Center Clinical Trials Referral Office

855-776-0015