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Waldenstrom MacroglobulinemiaPhase 2NCT05190705

Loncastuximab Tesirine in WM

A Phase 2 study testing Loncastuximab Tesirine and Dexamethasone in people with Waldenstrom Macroglobulinemia, run by Shayna Sarosiek, MD at 4 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

This study is being done to examine the safety and effectiveness of loncastuximab tesirine as a possible treatment for participants with Waldenström Macroglobulinemia (WM). The name of the study drug involved in this study is: Loncastuximab tesirine Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Waldenstrom Macroglobulinemia
What is being tested?
Loncastuximab Tesirine and Dexamethasone
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
4 sitesUnited States
Study dates
17 Feb 2022to 1 Aug 2028
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Clinicopathological diagnosis of Waldenström Macroglobulinemia
  • Symptomatic disease meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenström macroglobulinemia.
  • At least 2 prior lines of treatment, including an anti-CD20 monoclonal antibody-containing regimen and a BTK inhibitor.
  • Age 18 years or older
  • Measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum serum IgM level of > 2 times the upper limit normal.
  • ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
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  • Women of childbearing potential: Females of childbearing potential (FCBP) must agree to use two reliable forms of contraception simultaneously or have or will have complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) while participating in the study; and 2) for at least 9 months after discontinuation from the study. FCBP must be referred to a qualified provider of contraceptive methods if needed.
  • Men must agree to use a latex condom during sexual contact with a female of childbearing potential (FCBP) even if they have had a successful vasectomy 1) while participating in the study; and 2) for at least 6 months after discontinuation from the study.
  • Participants must have normal organ and marrow function as defined below:
  • Absolute neutrophil count ≥1000/ uL. Growth factors are not permitted <14 days prior to C1D1.
  • Platelets ≥50,000/ uL. Platelet transfusions are not permitted <14 days prior to C1D1.
  • Hemoglobin ≥ 7 g/dL. RBC transfusions are not permitted <14 days prior to C1D1.
  • Total bilirubin ≤ 1.5 X ULN, or ≤3 x ULN with documented liver metastases and/or Gilbert's Disease
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal, or ≤5 X ULN with documented liver metastases
  • Creatinine clearance ≥ 30 ml/min using Cockcroft/Gault formula
  • Able to adhere to the study visit schedule and other protocol requirements.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Prior treatment with CD19 targeted therapy.
  • Participants who are receiving any other investigational agents.
  • Clinically significant third space fluid accumulation (i.e., ascites requiring drainage or pleural effusion that is either requiring drainage or associated with shortness of breath) unless proven by cytology to be malignant due to WM.
  • Pregnant or breastfeeding.
  • Participants with known CNS lymphoma.
  • Participants with known history of Human Immunodeficiency Virus (HIV), chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring active treatment. Note: Participants with serologic evidence of prior vaccination to HBV (i.e., HBs Ag-, and anti-HBs+ and anti-HBC-) and positive anti-HBc from IVIG may participate.
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  • Significant cardiovascular disease defined as:
  • Unstable angina within the past 6 months, or
  • History of myocardial infarction within the past 6 months
  • Any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or
  • Uncontrolled or symptomatic arrhythmias
  • Participants with a history of Stevens-Johnson syndrome (SJS) or Toxic Epidermal Necrolysis (TEN)
  • Concurrent systemic immunosuppressant therapy.
  • Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
  • Recent infection requiring systemic treatment that was completed ≤ 14 days before the first dose of the study drug.
  • Major surgery within 4 weeks of first dose of study drug.
  • Participants with ongoing alcohol or drug abuse.
  • History of a non-lymphoma malignancy, except adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer, other adequately treated stage 1 or 2 cancer currently in complete remission, or any other cancer that is in a complete remission.
  • Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, EKG finding, or laboratory abnormality that, in the investigator's opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism or excretion of the study drug; or impair the assessment of study results.
  • Participants with ongoing >grade 1 toxicities from prior therapy (alopecia any grade and/or grade 2 neuropathy are permitted).
  • Participants with clinically significant history of liver disease, including cirrhosis or hepatitis (viral, autoimmune, etc).
  • Participants who are unwilling or unable to comply with the protocol.

Trial locations and contacts

4 sites in 1 country.

United States4 sites

  • Dana Farber Cancer Institute

    Boston, Massachusetts, 02115

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

  • Mayo Clinic

    Rochester, Minnesota, 55905

  • Fred Hutch

    Seattle, Washington, 98109

Other trials in United States

About this study

Official title: A Phase II Study Evaluating Loncastuximab Tesirine in Patients With Previously Treated Waldenström Macroglobulinemia

This study is being done to examine the safety and effectiveness of loncastuximab tesirine as a possible treatment for participants with Waldenström Macroglobulinemia (WM).

The name of the study drug involved in this study is:

  • Loncastuximab tesirine
Read the detailed description

This is a single-arm, open-label, phase II study to evaluate the safety and efficacy of loncastuximab tesirine in patients with Waldenström Macroglobulinemia (WM) who have received at least 2 prior treatments, including an anti-CD20 antibody such as rituximab and a BTK inhibitor such as ibrutinib.

The U.S. Food and Drug Administration (FDA) has not approved loncastuximab tesirine for Macroglobulinemia (WM) but it has been approved for other uses. Loncastuximab tesirine is a type of therapy called an antibody drug conjugate. This type of treatment is an antibody to CD19, a protein that is typically found on B-cells and plasma cells in patients with Macroglobulinemia (WM). This is a targeted therapy that uses an antibody (immunoglobulin) to deliver a toxin directly to the cancer.

The research study procedures include screening for eligibility and study treatment including evaluations and follow up visits.

It is expected that about 36 people will take part in this research study.

ADC Therapeutics is supporting this research study by providing funding and the study drug.

Being tested
Loncastuximab Tesirine, Dexamethasone
Keywords
Waldenstrom Macroglobulinemia
Medical subject headings
Waldenstrom Macroglobulinemia

What participants receive

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

  • Loncastuximab TesirineDrug

    Also called Zynlonta

    Administered by intravenous infusion

  • DexamethasoneDrug

    Also called Decadron, Dexamethasone Intensol, Dexpak, Taperpak

    Taken orally or administered by intravenous infusion

Study groups in NCT05190705
Study groupRoleWhat they receive
Loncastuximab Tesirine + DexamethasoneExperimentalParticipants will be given * Loncastuximab Tesirine on Day 1 of every 28 day study cycle and continue for up to 6 cycles. Participants will also receive pre-medications to reduce the chance of having a sensitivity reaction to the study treatment. Participants who tolerate the study treatment without a reaction may have pre-medications changed per determination of their doctor. * Dexamethasone will be given prior to study treatment on Day -1 or up to 2 hours prior to loncastuximab tesirine and the day after treatment
Receives: Drug: Loncastuximab Tesirine; Drug: Dexamethasone

What is being measured

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

  1. Overall Response Rate

    Overall Response Rate= Minor response (>25%-50% reduction in serum IgM from baseline) + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).

    Measured: 4 weeks up to 6 months

Secondary outcomes (15)

  1. Number of Participants With Complete Response

    A complete response is defined as having resolution of WM related symptoms, normalization of serum IgM levels with complete disappearance of IgM paraprotein by immunofixation, and resolution of any adenopathy or splenomegaly.

    Measured: 6 months

  2. Number of Participants With Very Good Partial Response

    Very Good Partial Response (VGPR): is defined as ≥90% reduction in serum IgM levels, or normalization of serum IgM levels.

    Measured: 6 months

  3. Number of Participants With Partial Response

    Partial response (PR) is defined as achieving a ≥50% reduction in serum IgM levels.

    Measured: 6 months

  4. Number of Participants With Minor Response

    Minor Response (MR): A minor response (MR) is defined 25-49% reduction in serum IgM levels.

    Measured: 6 months

  5. Number of Participants With Stable Disease

    Stable disease is defined as having <25% increase in serum IgM levels and <25% reduction in serum IgM levels

    Measured: 6 months

  6. Progression Free Survival

    Amount of time following loncastuximab administration until >25% increase in serum IgM

    Measured: 3 years

  7. Bone marrow response

    Absolute change in bone marrow burden of disease from baseline

    Measured: 6 months

  8. Overall Response Rate Among Participants Without MYD88 Mutations

    Overall Response Rate in participants who tested negative for a MYD88 mutation= Minor response (>25%-50% reduction in serum IgM from baseline) + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).

    Measured: 6 months

  9. Overall Response Rate Among Participants Without CXCR4 Mutations

    Overall Response Rate in participants who tested negative for a CXCR4 mutation= Minor response (>25%-50% reduction in serum IgM from baseline) + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).

    Measured: 6 months

  10. Number of Participants With Treatment-related Adverse Events

    Number of participants who experienced an adverse event while on loncastuximab tesirine

    Measured: 6 months

  11. Number of Participants With IgM Flare

    Number of participants who experienced an IgM Flare while on loncastuximab tesirine

    Measured: 6 months

  12. Number of Participants With Tumor Lysis Syndrome

    Number of participants who experienced Tumor Lysis Syndrome while on loncastuximab tesirine

    Measured: 6 months

  13. Impact of loncastuximab tesirine in the participants' quality of life

    Quality of life questionnaire European Organisation for Research and Treatment of Cancer. Scores range from 0-100 with high scores indicating a better outcome.

    Measured: 6 months

  14. Overall Response Rate Among CXCR4 Mutated Participants

    Overall Response Rate for participants who tested positive for a CXCR4 mutation= Minor response (>25%-50% reduction in serum IgM from baseline) + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).

    Measured: 6 months

  15. Overall Response Rate Among Participants With MYD88 Mutations

    Overall Response Rate in participants who tested positive for a MYD88 mutation= Minor response (>25%-50% reduction in serum IgM from baseline) + Partial Response (>50-90% reduction in serum IgM from baseline) + Very Good Partial Response (>90% reduction in serum IgM from baseline) + Complete Response (resolution of all symptoms, normalization of serum IgM with disappearance of IgM paraprotein, resolution of any adenopathy or splenomegaly).

    Measured: 6 months

Timeline

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

  1. First posted13 Jan 2022
  2. Study start17 Feb 2022
  3. Primary completion1 May 2026
  4. Study completion1 Aug 2028 (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
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05190705
Sponsor's protocol ID
21-622
Status last verified
May 2026
First submitted
29 Dec 2021
Last updated
20 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: \[contact information for Sponsor Investigator or designee\]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Loncastuximab Tesirine and Dexamethasone in people with Waldenstrom Macroglobulinemia, run by Shayna Sarosiek, MD at 4 sites 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 17 inclusion and 22 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: under way, not looking for participants, as of the sponsor's last update on 20 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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?

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?

Overall Response Rate (time frame: 4 weeks up to 6 months). 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 NCT05190705.

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 20 May 2026.

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