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Waldenström MacroglobulinemiaPhase 2NCT04463953

Zanubrutinib, Ixazomib and Dexamethasone in Patients With Treatment Naive Waldenstrom's Macroglobulinemia

A Phase 2 study testing Zanubrutinib,Ixazomib and Dexamethasone in people with Waldenström Macroglobulinemia, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This study aims to evaluate the efficacy of BTK inhibitor Zanubrutinib combined with Ixazomib and Dexamethasone (ZID) for the newly diagnosed Waldenstrom Macroglobulinemia. This ZID regimen will be given up to 24 months and stopped for observation. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Waldenström Macroglobulinemia
What is being tested?
Zanubrutinib,Ixazomib and Dexamethasone
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
1 siteChina
Study dates
1 Jun 2020to 6 Dec 2022
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • The gender of the patient is not limited, and the age is ≥18 years old;
  • Must meet WM's diagnostic standards;
  • The patient is an untreated or patient who has not undergone standard treatment. The specific conditions are as follows:
  • No combined chemotherapy with BR, RCD, VRD, CHOP and COP
  • No treatment regimen containing fludarabine
  • Chlorambucil or cyclophosphamide for less than 4 weeks (alone or in combination with adrenal glucocorticoids)
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  • The above treatment did not reach the treatment response (MR)
  • If the above treatment has been applied, the treatment needs to be stopped for 2 weeks before entering the group to start treatment
  • The indications for the treatment of indolent lymphoma mainly include (at least one of the following conditions):
  • Symptomatic hyperviscosity;
  • symptomatic peripheral neuropathy;
  • Amyloidosis;
  • Cold agglutinin disease; cryoglobulinemia;
  • Disease-related cytopenia (Hb<100 g/L, PLT<100×10^9/L);
  • giant lymph nodes;
  • Those with systemic systemic symptoms: for two weeks/recurrent fever (above 38℃) and not caused by infection, or Night sweats and/or weight loss >10% within 6 months;
  • The disease progresses rapidly, for example, the lymph nodes increase by more than 50% within 2 months, and/or peripheral blood lymphocytes absolute value doubling time <6 months, and/or rapid hemoglobin or platelet non-autoimmune causes slow down
  • When there is evidence that the disease has transformed.
  • ECOG score ≤ 2 points
  • Laboratory examination: neutrophils ≥ 0.75×10^9/L; platelets ≥ 50×10^9/L; total bilirubin ≤ 2.5 times upper limit; alanine aminotransferase/aspartate aminotransferase ≤3 times upper limit. Creatinine clearance rate ≥ 30ml/min.
  • The patient's expected survival time is ≥ 3 months.

Who cannot join

  • Malignant tumors (including active central nervous system lymphoma) other than B-NHL have been diagnosed or treated within the past year;
  • There is clinical evidence that large cell lymphoma transformation has occurred;
  • Non-lymphoma-related liver and kidney damage: alanine aminotransferase (ALT)> 3 times the upper limit of normal value, aspartate aminotransferase (AST)> 3 times the upper limit of normal value, total bilirubin (TBIL)> upper limit of normal value 2 Times, serum creatinine clearance rate <30ml/min;
  • Other serious medical conditions will affect the study (such as uncontrolled diabetes, gastric ulcers, other serious cardiopulmonary diseases, etc.). The decision-making power belongs to the researcher;
  • Known history of infection with human immunodeficiency virus (HIV) or active hepatitis B virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics.
  • Central nervous system dysfunction with clinical manifestations or central invasion (Bing-Neel syndrome);
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  • Patients who have undergone major surgery (not including lymph node biopsy) within the past 14 days or expected major surgery during treatment;
  • Inability to swallow capsules or suffer from malabsorption syndrome, diseases that significantly affect gastrointestinal function, have undergone gastric or small bowel resection, symptomatic inflammatory bowel disease or ulcerative colitis, partial or complete intestinal obstruction.
  • Need to receive strong cytochrome P450 (CYP) 3A inhibitor treatment.
  • Women who are pregnant or breastfeeding, women of childbearing age who have not taken contraception;
  • Allergy to the drugs used.

Trial locations and contacts

1 site in 1 country.

China1 site

  • Institute of Hematology & Blood Diseases Hospital

    Tianjin, Tianjin Municipality, 300020

Other trials in China

About this study

Official title: A Phase 2 Clinical Trial to Evaluate the Efficacy of Zanubrutinib Plus Ixazomib and Dexamethasone in Newly Diagnosed Symptomatic Waldenström Macroglobulinemia

This study aims to evaluate the efficacy of BTK inhibitor Zanubrutinib combined with Ixazomib and Dexamethasone (ZID) for the newly diagnosed Waldenstrom Macroglobulinemia. This ZID regimen will be given up to 24 months and stopped for observation. We propose this combination will improve the deep remission (≥VGPR) compared to single Zanubrutinib or IRD regimen and can be a time-limited regimen which will reduce the life-time therapy and benefit the patients.

Read the detailed description

As Waldenstrom Macroglobulinemia cells always have two or three components tumor cells, including lymphocyte, Lymphoplasmacytic cells and plasma cells. We designed a oral regimen to target both lymphoma cells (Zanubrutinib) and plasma cells (Ixazomib plus Dexamethasone) to eliminate the tumor cells of WM. We propose this combination will improve the deep remission of WM (≥VGPR) . Zanubrutinib will be given 160mg Bid per day, up to 24 months, Ixazomib 4mg per week and Dexamethasone 20mg per week for three weeks, every 4 weeks one course. ID will be given 6 course as introduction and then one course every 12 weeks for up to 24 months. At the last ID course, Zanubrutinib will be stopped. The last ID course is to prevent the bounce of IgM because of Zanubrutinib discontinue.

Being tested
Zanubrutinib,Ixazomib and Dexamethasone
Keywords
Waldenström Macroglobulinemia, Zanubrutinib, Ixazomib, Dexamethasone
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Zanubrutinib,Ixazomib and DexamethasoneDrug

    Zanubrutinib, 160mg orally, twice a day; Ixazomib, 4 mg orally, day 1, 8, 15; Dexamethasone, 20mg orally, days 1, 8, 15；Ixazomib and dexamethasone every 4 weeks of a cycle, with induction of 6 cycles, and then maintain every 12 weeks, up to 6 cycles (96 cycles in total). Zanubrutinib is taken orally twice a day for up to 96 cycles, with a reduction in the last ID cycle. ZID regimen will continue 6 cycles after reaching the maximum response after introduction section.

Study groups in NCT04463953
Study groupRoleWhat they receive
ZID regimenExperimentalZanubrutinib, 160mg orally, twice a day; Ixazomib, 4 mg orally, day 1, 8, 15; Dexamethasone, 20mg orally, days 1, 8, 15.
Receives: Drug: Zanubrutinib,Ixazomib and Dexamethasone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Deep remission response rate

    ≥VGPR after 6 cycles introduction

    Measured: up to 5 years

Secondary outcomes (6)

  1. Complete response (CR)

    Disappearance of monoclonal protein on immunofixation (both serum and urine); No histologic evidence of bone marrow involvement; Resolution of adenopathy and/or organomegaly on CT; Resolution of clinical signs or symptoms attributed to WM/LPL.

    Measured: up to 12 months

  2. Progress-free survival (PFS)

    the time from treatment initiation until disease progression or death

    Measured: up to 5 years

  3. Duration of response (DoR)

    the time from best response (R) to progression/death (P/D)

    Measured: up to 5 years

  4. Overall survival (OS)

    The percentage of patients in treatment group who are still alive for a certain period of time after they were diagnosed with Waldenstrom's Macroglobulinemia.

    Measured: up to 36 months

  5. Time to next treatment (TTNT)

    time from end of primary treatment to institution of next therapy

    Measured: up to 5 years

  6. Overall response

    minimor response+partial response+VGPR+CR

    Measured: up to 5 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Jul 2020
  2. Study start1 Jun 2020
  3. Primary completion6 Dec 2022
  4. Study completion6 Dec 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Zanubrutinib, 160mg orally, twice a day; Ixazomib, 4 mg orally, day 1, 8, 15; Dexamethasone, 20mg orally, days 1, 8, 15.
Masking
None (open label)
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04463953
Sponsor's protocol ID
IIT2020002
Status last verified
May 2024
First submitted
4 Jul 2020
Last updated
11 Feb 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Treon SP, Xu L, Guerrera ML, Jimenez C, Hunter ZR, Liu X, Demos M, Gustine J, Chan G, Munshi M, Tsakmaklis N, Chen JG, Kofides A, Sklavenitis-Pistofidis R, Bustoros M, Keezer A, Meid K, Patterson CJ, Sacco A, Roccaro A, Branagan AR, Yang G, Ghobrial IM, Castillo JJ. Genomic Landscape of Waldenstrom Macroglobulinemia and Its Impact on Treatment Strategies. J Clin Oncol. 2020 Apr 10;38(11):1198-1208. doi: 10.1200/JCO.19.02314. Epub 2020 Feb 21.

    PubMed 32083995

  • Treon SP, Xu L, Hunter Z. MYD88 Mutations and Response to Ibrutinib in Waldenstrom's Macroglobulinemia. N Engl J Med. 2015 Aug 6;373(6):584-6. doi: 10.1056/NEJMc1506192. No abstract available.

    PubMed 26244327

  • Castillo JJ, Meid K, Gustine JN, Dubeau T, Severns P, Hunter ZR, Yang G, Xu L, Treon SP. Prospective Clinical Trial of Ixazomib, Dexamethasone, and Rituximab as Primary Therapy in Waldenstrom Macroglobulinemia. Clin Cancer Res. 2018 Jul 15;24(14):3247-3252. doi: 10.1158/1078-0432.CCR-18-0152. Epub 2018 Apr 16.

    PubMed 29661775

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zanubrutinib,Ixazomib and Dexamethasone in people with Waldenström Macroglobulinemia, run by Institute of Hematology & Blood Diseases Hospital, China at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Deep remission response rate (time frame: up to 5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04463953, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2026.

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