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Waldenstrom MacroglobulinemiaPhase 2NCT07882173

Epcoritamab as Consolidative Therapy for Waldenstr(SqrRoot)(Delta)m Macroglobulinemia (WM) Treated With a Bruton Tyrosine Kinase Inhibitor (BTKi)

A Phase 2 study testing epcoritamab in people with Waldenstrom Macroglobulinemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

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
Search all trials

Trial summary

Background: Waldenstrom macroglobulinemia (WM) is a type of blood cancer. It causes the blood to get thicker, which slows circulation and makes it harder to carry oxygen and other substances around the body. WM is treated with drugs called Bruton tyrosine kinase inhibitors (BTKi). Read more about this study

Who is it for?
Ages 18 to 100 years
Conditions the study is for
Waldenstrom Macroglobulinemia
What is being tested?
epcoritamab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
24 participants
Where
1 siteUnited States
Study dates
11 Nov 2026to 1 Nov 2033
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 18 to 100 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients must meet the following entry criteria to be eligible to participate in the study:
  • Age >=18 years
  • Ability to comprehend the investigational nature of the study and provide informed consent
  • Diagnosis of WM according to 11th International Workshop on WM (IWWM-11) (19)
  • Presence of an IgM monoclonal protein
  • Bone marrow involvement by lymphoplasmacytic lymphoma
Show all 51Show fewer
  • Presence of MYD88 L265P mutation
  • Currently receiving a BTKi, zanubrutinib or ibrutinib, for >=12 months
  • Able to obtain a commercial supply of BTKi
  • Achieved partial response, minor response, or stable disease on a BTKi per IWWM-11 response criteria (19)
  • A female participant is eligible to participate if not pregnant or breastfeeding, and >=1 of the following conditions applies:
  • Is not a woman of childbearing potential (WOCBP)
  • OR
  • Is a WOCBP and
  • Uses a contraceptive method
  • Has a negative highly sensitive serum pregnancy test within 7 days before the first dose of study intervention.
  • Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 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 >=4 weeks and have undetectable HBV viral load prior to study entry.
  • Note: Participants should remain on anti-viral therapy throughout study intervention and for at least 12 months following discontinuation of epcoritamab. Hepatitis B screening tests should include HBsAg and anti-HBV.
  • Participants who received treatment for HCV that was intended to eradicate the virus are eligible if hepatitis C RNA levels are undetectable.
  • COVID 19 eligibility criteria:
  • Subject has no known active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. If a subject has signs/symptoms suggestive of SARS-CoV-2 infection or have had recent known exposure to someone with SARS-CoV-2 infection, the subject must have a negative molecular (e.g., PCR) test, or 2 negative antigen test results at least 24 hours apart, to rule out SARS-CoV-2 infection.
  • Subjects who do not meet SARS-CoV-2 infection eligibility criteria must be screen failed and may only rescreen after they meet the following SARS-CoV-2 infection viral clearance criteria:
  • No signs/symptoms suggestive of active SARS-CoV-2 infection
  • Negative molecular (e.g., PCR) result or 2 negative antigen test results at least 24 hours apart
  • Adequate organ function as defined below.
  • Adequate Organ Function Laboratory Values
  • System
  • Laboratory Value
  • Hematological
  • Absolute neutrophil count (ANC)
  • >=1000/microL (a)
  • Platelets
  • >=75000/microL or >=50000/microLin the presence of bone marrow involvement or splenomegaly (a)
  • Hemoglobin
  • >=8 g/dL (a)
  • Renal
  • Creatinine
  • <=1.5 x ULN or eGFR >=30 mL/min
  • Hepatic
  • Total bilirubin
  • <=1.5 x ULN unless due to Gilbert's syndrome or controlled autoimmune hemolytic anemia (not requiring immunosuppressive other than <=20 mg of prednisolone daily)
  • AST and ALT
  • <=3 ULN
  • Coagulation
  • PT
  • aPTT
  • <=1.5 x ULN unless participant is receiving anticoagulant therapy
  • eGFR=estimated glomerular filtration rate; ALT =alanine aminotransferase; AST =aspartate aminotransferase; ULN=upper limit of normal; INR=international normalized ratio; PT=prothrombin time; aPTT=activated partial thromboplastin time
  • Growth factor and/or transfusion support is allowed to meet this requirement at Screening only if directly attributable to WM infiltration of the bone marrow, proven by bone marrow biopsy

Who cannot join

  • An individual who meets any of the following criteria will be excluded from participation in this study:
  • Active CNS involvement, including Bing-Neel syndrome
  • Active HBV/HCV infection.
  • Infection with HIV-1 or HIV-2. Exception: patients with well-controlled HIV (e.g., CD4 >350/mm^3 and undetectable viral load) are eligible.
  • Gastrointestinal dysfunction that may affect drug absorption (e.g., gastric bypass surgery, gastrectomy).
  • Ongoing active bacterial, viral, fungal, mycobacterial, parasitic, or other infection requiring systemic treatment (excluding prophylactic treatment) at the time of enrollment or within the previous 2 weeks prior to the first dose of epcoritamab, including COVID-19 infection. Note that a past COVID-19 infection may be a risk factor, but if resolved and the subject is vaccinated, it may be allowable to enroll the Subject.
Show all 35Show fewer
  • Stroke or intracranial hemorrhage within 6 months of screening
  • Hypertensive urgency or emergency
  • Active, clinically significant cardiovascular disease including:
  • Uncontrolled or symptomatic arrhythmias
  • Class 3 or 4 congestive heart failure as defined by New York Heart Association Functional Classification
  • Association and/or known decreased ejection fraction <45%
  • Myocardial infarction, unstable angina or acute coronary syndrome within 6 months of screening.
  • History of Mobitz II second-degree or third-degree heart block without a permanent pacemaker in place.
  • QTcF >450 msecs based on Fridericia's formula
  • Note: QTcF value may be calculated as the numerical average of up to 3 separate readings for eligibility).
  • Known allergy/sensitivity to epcoritamab
  • History of severe bleeding disorder defined as an ongoing congenital or acquired condition that leads to an increased likelihood of bleeding (i.e., von Willebrand's disease or hemophilia).
  • 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.
  • Currently being treated with the following drugs:
  • 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.
  • Has received prior systemic anti-WM therapy besides a BTKi within 3 half-lives or 4 weeks (if prior therapy was a monoclonal antibody) of start of epcoritamab.
  • Has received prior radiotherapy within 2 weeks of start of epcoritamab 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 28 days before the first dose of epcoritamab. Administration of killed vaccines are allowed.
  • Patients requiring ongoing treatment with warfarin within 7 days of start of epcoritamab
  • Patients who have received > 140 mg of prednisone for 14 days prior to first dose of epcoritamab or those requiring > 10 mg prednisone (or equivalent) daily, unless needed for disease control.
  • Confirmed history or current autoimmune disease or other diseases resulting in permanent immunosuppression or requiring permanent immunosuppressive therapy. Low-dose (<=10 mg/day) prednisolone (or equivalent) for rheumatoid arthritis or similar conditions is allowed.
  • Enrolled on another therapeutic clinical trial for WM at the start of epcoritamab. Concurrent enrollment on another therapeutic clinical trial or any trial designed to impact the efficacy of anti-cancer therapy is prohibited.
  • 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.

Lymphoid Malignancies Team Study Coordin contact

(301) 827-1203

nhlbidi-rocdlmtrn@nih.gov

Laura S Samples, M.D. contact

(301) 827-1203

laura.samples@nih.gov

United States1 site

  • National Institutes of Health Clinical Center

    Bethesda, Maryland, 20892

    NIH Clinical Center Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov

Other trials in United States

About this study

Official title: Epcoritamab as Consolidative Therapy for Waldenstrom Macroglobulinemia (WM) Treated With a Bruton Tyrosine Kinase Inhibitor (BTKi)

Background:

Waldenstrom macroglobulinemia (WM) is a type of blood cancer. It causes the blood to get thicker, which slows circulation and makes it harder to carry oxygen and other substances around the body. WM is treated with drugs called Bruton tyrosine kinase inhibitors (BTKi). Although BTKis are effective, it may be possible for someone on a BTKi to get a deeper response to treatment by adding another medication.

Read more

Objective:

To test a new drug (epcoritamab) in people with WM who are currently also on a BTKi.

Eligibility:

People aged 18 years or older who have WM. They must have been taking a BTKi for a year or more.

Design:

Participants will be screened. They will have blood and urine tests. They will have imaging scans and a test of their heart function. They may have a bone marrow biopsy: A large needle will be used to remove a sample of the soft tissue and fluids from inside the hip bone.

Epcoritamab is injected under the skin, normally on the lower belly or thigh. Participants will be treated in 28-day cycles while they continue their normal BTKi. They will have 12 treatment cycles. During the first cycle, they will come to the clinic to get an injection once a week for 4 weeks. After that, they will get 1 injection on the first day of each cycle. Blood tests and imaging scans will be repeated at study visits. A saliva sample will be taken for genetic testing.

If a participant has a very good response to 1 year of epcoritamab in combination with their BTKi, they will stop their BTKi when epcoritamab treatment ends. After their last treatment with epcoritamab, participants will continue to have follow-up visits. Tests, including a bone marrow biopsy, may be repeated. Follow-up visits will continue every 6 months for at least 3 and a half years.

Read the detailed description

Study Description:

This is a phase 2 study of adding epcoritamab as consolidative therapy for subjects with Waldenstrom macroglobulinemia (WM) receiving treatment with a Bruton tyrosine kinase inhibitor (BTKi), zanubrutinib or ibrutinib. Subjects will be treated with epcoritamab for twelve 28-day cycles. For cycle 1, patients will receive epcoritamab subcutaneously (SC) with step-up dosing (SUD; 0.16 mg on C1D1, 0.8 mg on C1D8, 3 mg on C1D15, 48 mg on C1D22). The first 3 subjects will start treatment with epcoritamab >=4 weeks apart and be hospitalized for 24 hours after the first full dose of 48 mg for observation. In the absence of grade >=3 cytokine release syndrome (CRS), subsequent subjects will be treated on an outpatient basis. Epcoritamab 48 mg SC will be administered every 4 weeks from cycles 2 to 12.

Subjects achieving complete remission (CR) or very good partial remission (VGPR) by serum IgM after 12 cycles of epcoritamab will be evaluated by bone marrow biopsy and aspirate 2 months after the last dose of epcoritamab, and elect to discontinue BTKi therapy if CR/VGPR is confirmed. For subjects who do not attain CR/VGPR, BTKi will continue as per standard of care.

Objectives:

Primary objective:

-Evaluate the efficacy of epcoritamab as consolidative therapy in WM treated with a BTKi

Secondary objectives:

  • Evaluate the safety of epcoritamab as consolidative therapy in WM treated with a BTKi
  • Evaluate other parameters of efficacy of epcoritamab as consolidative therapy in WM treated with a BTKi

Endpoints:

Primary Endpoint:

-Rate of CR/VGPR after 12 cycles of epcoritamab in WM treated with a BTKi

Secondary Endpoint:

  • Rate of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and IgM flare
  • Incidence and severity of treatment-emergent adverse events (TEAEs)
  • Progression-free survival (PFS)
  • Duration of response after BTKi discontinuation
  • Overall survival (OS)
Being tested
epcoritamab
Keywords
Bruton tyrosine kinase inhibitor, consolidative therapy, Epcoritamab, zanubrutinib, Ibrutinib
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

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

  • epcoritamabDrug

    Step-up epcoritamab dosing during cycle 1, followed by 48 mg every 4 weeks for cycles 2-12

Study groups in NCT07882173
Study groupRoleWhat they receive
EpcoritamabExperimentalEpcoritamab will be administered as consolidative therapy in adults who have been receiving zanubrutinib or ibrutinib.
Receives: Drug: epcoritamab

What is being measured

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

  1. Rate of complete remission (CR) or very good partial remission (VGPR)

    CR: No detectable monoclonal IgM, normal bone marrow morphology with no lymphoplasmacytic lymphoma involvement, and resolution of any baseline extramedullary disease.VGPR: At least a 90% reduction in serum IgM from baseline or a serum IgM level within the normal range.

    Measured: 12 cycles (approximately 12 months after treatment begins)

Secondary outcomes (7)

  1. Overall survival (OS)

    Time from treatment initiation to death from any cause.

    Measured: From the first dose of epcoritamab until death or up to 5 years after the first dose.

  2. Duration of response (DOR) after BTKi discontinuation

    The length of time that a confirmed CR or VGPR is maintained after BTKi therapy is discontinued.

    Measured: After BTKi discontinuation until loss of response, progression, death, or initiation of subsequent therapy.

  3. Progression-free survival (PFS)

    Time from treatment initiation to disease progression or death from any cause.

    Measured: From the first dose of epcoritamab until progression or death.

  4. Treatment-emergent adverse events (TEAEs)

    Any new or worsened unfavorable medical occurrence after study treatment begins, regardless of whether it is considered treatment-related.

    Measured: From the first dose of epcoritamab through 60 days after the last dose, or until new systemic anticancer therapy.

  5. IgM flare

    Measured through serial serum IgM.

    Measured: Baseline, during treatment, after treatment, and following BTKi discontinuation.

  6. Immune effector cell associated neurotoxicity syndrome (ICANS)

    ICANs will be assessed using the 10-point ICE tool.

    Measured: From the first epcoritamab dose through treatment and safety follow-up, approximately 60 days after the last dose.

  7. Cytokine release syndrome (CRS)

    CRS will be graded using the ASTCT CRS criteria.

    Measured: From the first epcoritamab dose through treatment and safety follow-up, approximately 60 days after the last dose.

Timeline

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

  1. First posted20 Oct 2026
  2. Study start11 Nov 2026 (estimated)
  3. Primary completion1 Nov 2030 (estimated)
  4. Study completion1 Nov 2033 (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
24 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07882173
Sponsor's protocol ID
10002492
Other IDs
002492-H
Status last verified
15 Oct 2026
First submitted
19 Oct 2026
Last updated
6 Nov 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing epcoritamab in people with Waldenstrom Macroglobulinemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.

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 51 inclusion and 35 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 6 Nov 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 United States. 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 Lymphoid Malignancies Team Study Coordin ((301) 827-1203, nhlbidi-rocdlmtrn@nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of complete remission (CR) or very good partial remission (VGPR) (time frame: 12 cycles (approximately 12 months after treatment begins)). 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 NCT07882173.

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 6 Nov 2026.

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