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Waldenstrom MacroglobulinemiaPhase 2NCT07464210

Nemtabrutinib, Bortezomib, and Rituximab for WM

A Phase 2 study testing NEBULA in people with Waldenstrom Macroglobulinemia, run by Seoul National University Hospital at 1 site in South Korea.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

This is a phase II (2 parts), open-label, single arm, multicenter study to evaluate the efficacy and safety of nemtabrutinib in combination with bortezomib and rituximab Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Waldenstrom Macroglobulinemia
What is being tested?
NEBULA
Could I receive a placebo?
No, everyone receives an active treatment
How many people
19 participants
Where
1 siteSouth Korea
Study dates
1 Jun 2026to 1 Aug 2030
Phase
Phase 2
Are there results?
Not yet: the study is under way

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

Who may be able to join

  • Participants are eligible to be included in the study only if all of the following criteria apply:
  • Confirmed diagnosis of WM in accordance with the consensus panel of the IWWM (per local evaluation), and treatment naïve
  • Symptomatic disease meeting at least 1 of the recommendations from the IWWM for requiring treatment.
  • Measurable disease defined as serum monoclonal IgM > 0.5g/dL.
  • Is an individual of any sex/gender, who are at least 19 years of age on the day of signing informed consent (ICF).
  • Participants Assigned Male Sex at Birth
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  • If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
  • Nemtabrutinib: 12 days
  • Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent OR
  • Uses contraception as detailed below unless confirmed to be azoospermic (vasectomized or secondary to medical cause, documented from the site personnel's review of the participant's medical records, medical examination, or medical history interview) as detailed below:
  • Uses a penile/external condom plus nonparticipant of childbearing potential who is not currently pregnant and should also be advised of the benefit for that partner to use an additional method of contraception, as a condom may break or leak.
  • Note: Participants capable of producing ejaculate whose partner is pregnant or breastfeeding must agree to use penile/external condom during each episode of sexual activity in which the partner is at risk of drug exposure via ejaculate.
  • -- Contraceptive use by participants capable of producing sperm should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.
  • Participants Assigned Female Sex at Birth
  • A participant assigned female sex at birth is eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:
  • Is not a person of childbearing potential (POCBP) OR
  • Is a POCBP and:
  • Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or is abstinent from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis), as described in Appendix 3 during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:
  • Nemtabrutinib: 1 month
  • The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by POCBPs should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.
  • Has a negative highly sensitive pregnancy test (urine or serum) as required by local regulations within 24 hours (for urine test) or 72 hours (for serum test) before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. Additional requirements for pregnancy testing during and after study intervention are in Section X.
  • Abstains from breastfeeding during the study intervention period and for at least 30 days after study intervention with nemtabrutinib.
  • Medical history, menstrual history, and recent sexual activity has been reviewed by the investigator to decrease the risk for inclusion of a POCBP with an early undetected pregnancy.
  • The participant (or legally acceptable representative if applicable) has provided documented informed consent/assent for the trial.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
  • The ability to swallow and retain oral medication.
  • Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization.
  • Note: Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention. Hepatitis B screening tests should include HBsAg and anti-HBV. Hepatitis B screening tests are not required unless:
  • Known history of HBV infection
  • As mandated by local health authority
  • Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.
  • Participants must have completed curative anti-viral therapy at least 4 weeks prior to randomization.
  • Hepatitis C screening tests are not required unless:
  • Known history of HCV infection
  • As mandated by local health authority
  • Adequate organ function as defined in the following table (Table 5.1.1). Specimens must be collected within 7 days prior to randomization.
  • Table 5.1.1 Adequate organ function System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥500/µL a, b Platelets ≥25 000/µL a, b Hemoglobin ≥8 g/dL a, b Renal Creatinine OR Measured or calculated c creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × ULN OR
  • ≥30 mL/min for participant with creatinine levels >1.5 × institutional ULN Hepatic Total bilirubin ≤1.5 ×ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN AST (SGOT) and ALT (SGPT) ≤2.5 × ULN (≤5 × ULN for participants with liver metastases) Coagulation International normalized ratio (INR) OR prothrombin time (PT) Activated partial thromboplastin time (aPTT) ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
  • aGrowth factor and/or transfusion support is permissible to stabilize participant prior to study treatment if needed.
  • bNo lower limit if cytopenia is related to bone marrow involvement. cCreatinine clearance (CrCl) should be calculated per institutional standard. Note: This table includes eligibility-defining laboratory value requirements for treatment; laboratory value requirements should be adapted according to local regulations and guidelines for the administration of specific chemotherapies.

Who cannot join

  • The participant must be excluded from the study if the participant meets any of the following criteria:
  • Active HBV/HCV infection.
  • Positive for human immunodeficiency virus (HIV).
  • Gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy).
  • Active infection requiring systemic therapy, including IV antibiotics during screening. Participants may be rescreened followed completion of IV antibiotic course.
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
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  • QTc prolongation (defined as a QTcF >450 msecs) or other significant ECG abnormalities including second degree AV block type II, third degree AV block, or bradycardia (ventricular rate less than 50 beats/min).
  • A history of anaphylaxis or hypersensitivity to investigational products or components of investigational products (nemtabrutinib, bortezomib, rituximab).
  • History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding.
  • History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
  • NOTE: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder.
  • A POCBP who has a positive urine pregnancy test within 72 hours prior to allocation (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Prior use of any BTKi.
  • Prior exposure to proteasome inhibitors (bortezomib, ixazomib, carfilzomib).
  • Prior exposure to anti-CD20 antibody.
  • Currently being treated with the following drugs:
  • P-gp substrates with a narrow therapeutic index
  • CYP3A strong inducers
  • CYP3A strong inhibitors NOTE: A washout period of at least 5 times the half-life after the last dose of any of the above treatments is required for a participant to be eligible for study enrollment. A list of example in vivo substrates for specific CYP enzymes and P-gp is provided in Appendix 5.
  • NOTE: Refer to Appendix 5 regarding prohibited concomitant medications and potential drug interactions after participant randomization.
  • Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids.
  • Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease, with a 1-week washout, is permitted.
  • Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.
  • Note: Refer to Section 5.2.2 for information on COVID-19 vaccines
  • Is currently enrolled on another therapeutic clinical trial. Concurrent enrollment on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy is prohibited.
  • Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
  • Has not adequately recovered after 4 weeks from major surgery or has ongoing surgical complications.
  • Note: Biopsy and placement of central venous access devices are not considered major surgery.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ja Min Byun, MD, PhD contact

82-02-2072-7215

jaminbyun@snu.ac.kr

South Korea1 site

  • Seoul National University Hospital

    Seoul, 03080

    Ja Min Byun, MD PhD, 82-02-2072-7215, jaminbyun@snu.ac.kr

Other trials in South Korea

About this study

Official title: Nemtabrutinib, Bortezomib, and Rituximab for the Treatment of Waldenstrom's Macroglobulinemia (NEBULA)

This is a phase II (2 parts), open-label, single arm, multicenter study to evaluate the efficacy and safety of nemtabrutinib in combination with bortezomib and rituximab

Being tested
NEBULA
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

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

  • NEBULADrug

    Nemtabrutinib + Bortezomib + Rituximab

Study groups in NCT07464210
Study groupRoleWhat they receive
Treatment (NEBULA: Nemtabrutinib + Bortezomib + Rituximab) armExperimentalNemtabrutinib + Bortezomib + Rituximab
Receives: Drug: NEBULA

What is being measured

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

  1. Major response rate (MRR)

    Composite of complete response (CR) + very good partial response (VGPR) + partial response (PR) according to International Workshop on WM (IWWM)-11 response criteria

    Measured: At the end of Cycle 6 (each cycle is 28 days)

Secondary outcomes (5)

  1. Progression-free survival (PFS)

    Time from enrollment to first documentation of disease progression or death due to any cause, whichever occurs first

    Measured: through study completion, an average of 2 years

  2. Overall survival

    Time from enrollment to death from any cause

    Measured: through study completion, an average of 2 years

  3. Overall response rate (ORR)

    Composite of CR + VGPR + PR + minor response (MR) according to IWWM-11 response criteria

    Measured: At the end of Cycle 24 (each cycle is 28 days)

  4. complete response (CR) rate

    Response assessments will be based on the IWWM-11 criteria

    Measured: At the end of Cycle 6 and Cycle 24 (each cycle is 28 days)

  5. Time to response (TTR)

    Time to the first documentation of response (MR or better)

    Measured: through study completion, an average of 2 years

Timeline

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

  1. First posted11 Mar 2026
  2. Study start1 Jun 2026 (estimated)
  3. Primary completion1 Aug 2029 (estimated)
  4. Study completion1 Aug 2030 (estimated)

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
Masking
None (open label)
Enrolment
19 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07464210
Sponsor's protocol ID
NEBULA
Status last verified
Mar 2026
First submitted
2 Mar 2026
Last updated
11 Mar 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NEBULA in people with Waldenstrom Macroglobulinemia, run by Seoul National University Hospital at 1 site in South Korea.

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 40 inclusion and 29 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: opening soon, as of the sponsor's last update on 11 Mar 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 South Korea. 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?

This study is still under way. Results are not available in the source record yet.

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

Contact Ja Min Byun, MD, PhD (82-02-2072-7215, jaminbyun@snu.ac.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Major response rate (MRR) (time frame: At the end of Cycle 6 (each cycle is 28 days)). 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 NCT07464210.

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 Mar 2026.

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