ClinicalTrials.gov record NCT07791498
Teclistamab In Waldenstrom's Macroglobulinemia
A Phase 2 Study of Teclistamab in Relapsed or Refractory Waldenstrom's Macroglobulinemia
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AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This open-label Phase 2 study tests teclistamab in adults with relapsed or refractory Waldenstrom's macroglobulinemia who have received prior therapy. Up to 24 participants will receive subcutaneous teclistamab on days 1, 4, and 7 of a 14-day first cycle, then weekly in cycles 2–5 and less frequently in cycles 6–9, for a maximum of nine cycles. The study will record response rates, timing of responses, and safety, and will assess responses by MY88 and CXCR4 mutation combinations.
What it is studying. It tests whether teclistamab can produce tumor responses and evaluates safety, timing and strength of responses, including by MY88 and CXCR4 mutation combinations.
What the researchers hope to learn. Scientifically, the study aims to determine overall immunoglobulin M (IgM) response rates and objective response rate (ORR), assess safety and tolerability, measure time to any response and to major response, and estimate progression-free and overall survival. The study also aims to report response rates by the combination of MY88 and CXCR4 mutation status.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
The goal of this clinical trial is to assess the efficacy of teclistamab in participants with relapsed or refractory Waldenstrom's macroglobulinemia who have received prior therapy. This study also aims to assess the safety and tolerability of teclistamab, how quickly and to what extent response is seen in participants, how strong any clinical benefit of teclistamab might be, and determine the response to teclistamab based on the combination of MY88 and CXCR4 mutations. The main questions it aims to answer are:
- Will teclistamab be effective in treating Waldenstrom's macroglobulinemia?
- By targeting BCMA with teclistamab, will direct Waldenstrom's macroglobulinemia tumor death occur? Participants will receive teclistamab for up to 9 cycles (cycle 1 is 14 days, cycles 2-5 are 28 days, and cycles 6-9 are 56 days) or until their disease progresses, another illness or change in their condition prevents them from further receiving the treatment, they experience unacceptable side effects, they demonstrate an inability or unwillingness to receive the medication regimen, or they decide to withdraw from the study. Participants will be followed for up to 3 years from the last treatment.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Teclistamab
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- Clinicopathological diagnosis of WM per IWWM2 criteria.
- Meeting criteria for treatment per IWWM2 criteria.
- Relapsed or refractory WM with at least 1 prior line of treatment, including an anti-CD20 monoclonal antibody containing regimen or a BTK inhibitor.
- Patients should have received a prior BTK inhibitor (except for contraindications such as bulky disease, amyloidosis, significant medication interactions, or a history of severe bleeding).
- Participants with suspected or symptomatic hyperviscosity (e.g. nosebleeds, headaches, blurred vision) must undergo plasmapheresis prior to treatment initiation.
- Adults aged ≥18
- ECOG performance status ≤2 (Karnofsky ≥60%, see Appendix A)
- A female participant of childbearing potential must have a negative highly sensitive serum pregnancy test at screening and again either a serum or urine pregnancy test within 24 hours of the start of study treatment and must agree to further serum or urine pregnancy tests during the study.
- A female participant must be:
- Not of childbearing potential, or
- Of childbearing potential and practicing at least 1 highly effective method of contraception
- A male participant must wear a condom (with or without spermicidal foam/gel/film/ cream/suppository) when engaging in any activity that allows for passage of ejaculate to another person during the study and for 3 months after receiving the last dose of study treatment.
- Participants must meet the following organ and marrow function as defined below:
- Absolute neutrophil count ≥500/mcL; the patient may enroll below this threshold if neutropenia is believed to be caused by WM bone marrow involvement. Growth factors are not permitted <14 days prior to C1D1.
- Platelets ≥30,000/mcL believed to be caused by WM bone marrow involvement. Platelet transfusions are not permitted <14 days prior to C1D1.
- Hemoglobin ≥ 8 g/dL. RBC transfusions are not permitted <14 days prior to C1D1.
- Total bilirubin ≤ 1.5 X institutional ULN, or ≤3 x institutional ULN with documented liver metastases and/or Gilbert's Disease
- AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal
- Creatinine clearance ≥30 mL/min using the Cockcroft-Gault formula
- Ability to adhere to the study visit schedule and other protocol requirements.
- Ability to understand and the willingness to sign a written informed consent document.
Exclusion criteria
- Received any prior BCMA-directed therapy.
- Any serious medical condition, laboratory abnormality, uncontrolled intercurrent illness, or psychiatric illness/social condition that would prevent the participant from signing the informed consent form.
- Participants who are receiving any other investigational agents for this condition.
- Participants with known CNS lymphoma.
- Female participants who are pregnant, breastfeeding, or planning to become pregnant or breastfeed while enrolled in this study.
- History of HIV infection or active hepatitis B (chronic or acute) or hepatitis C infection.
- Patients with a history of HIV infection that is well controlled on antiretroviral therapy are eligible if all of the following criteria are met: (1) undetectable HIV viral load by standard clinical assay AND (2) CD4+ T cell count of >/=200 cells/microliter).
- Participants with occult or prior HBV infection (defined as positive total hepatitis B core antibody [HBcAb] and negative HBsAg) may be included if HBV DNA is undetectable, and if the participant is willing to take appropriate anti-viral prophylaxis as indicated and HBV DNA monitoring on study.
- Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
- 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.
- 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
- Concurrent systemic immunosuppressant therapy. Systemic steroids at doses <20mg prednisone per day are permitted.
- Concurrent systemic anti-Waldenstrom therapy.
- Active and/or ongoing autoimmune anemia and/or autoimmune thrombocytopenia (eg, idiopathic thrombocytopenia purpura).
- Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug.
- Active uncontrolled systemic bacterial, viral, fungal or parasitic infection (except for fungal nail infection), or other clinically significant active disease process which in the opinion of the Investigator and the Sponsor makes it undesirable for the patient to participate in the trial. Screening for chronic conditions is not required.
- Major surgery within 4 weeks of first dose of study drug.
- Participants with a known hypersensitivity to any of the excipients of Teclistamab.
- Participants with a history of non-compliance to medical regimens, which will render the administration of study drug hazardous or obscure the interpretation of toxicity or AEs.
- 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.
- Ongoing alcohol or drug addiction or any psychiatric condition(s) which would compromise ability to comply with study procedures.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Detailed description from the registry
This is an open label phase II study that will enroll 24 patients with relapsed or refractory Waldenstrom's macroglobulinemia after one or more lines of systemic therapy for WM, including an anti-CD20 monoclonal antibody-containing regimen or a BTK inhibitor. This research study is evaluating a less frequent and shorter dosing schedule of teclistamab compared to the approved dosing schedule for individuals with multiple myeloma, which includes more frequent dosing in early treatment cycles and continuing to receive teclistamab until disease progression or unacceptable side effects occur. Johnson \& Johnson is supporting this research study by providing the study drug, teclistamab, and funding for the clinical trial activities. The U.S. Food and Drug Administration (FDA) has not approved teclistamab for relapsed or refractory Waldenstrom's macroglobulinemia, but it has been approved to treat other types of multiple myeloma that has come back or been difficult to treat. Teclistamab is a type of antibody-based medication that attaches to both cancer cells and the body's T cells (a type of immune cell). By connecting the two, teclistamab bring T cells close enough to the cancer cells so they can activate and kill the cancer cells directly, without needing usual immune-system signals.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
Participants will receive teclistamab as subcutaneous injections into the abdomen: on days 1, 4, and 7 of a first 14-day cycle, then weekly during up to four 28-day cycles and up to four 56-day cycles (maximum nine cycles), or until treatment stops for disease progression, unacceptable side effects, inability to continue, or withdrawal. People with suspected or symptomatic hyperviscosity must undergo plasmapheresis before starting treatment. Female participants of childbearing potential will have pregnancy testing at screening, within 24 hours before the first dose, and during the study as required. Participants will have regular clinic visits with blood tests to measure IgM response and to monitor safety, and they will be followed for up to three years after their last dose.
How the study is structured. This is an interventional, open-label, single-group Phase 2 trial enrolling about 24 participants. All participants receive subcutaneous teclistamab following the schedule described (days 1, 4, 7 in cycle 1, then weekly for cycles 2–5, then less frequent dosing through cycle 9). The study measures blood-based IgM response rates (including objective response rate), timing of responses, adverse events, and longer-term outcomes such as progression-free and overall survival. Participants are followed for up to 3 years after their last treatment.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The registry lists this study under Waldenstrom's Macroglobulinemia. Does it apply to my diagnosis?
- The registry says recruitment has not started. When is it expected to open, and can I register interest now?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Waldenström macroglobulinemia
Important dates
- Study start
- Feb 19, 2027 (estimated)
- Primary completion
- Sep 1, 2027 (estimated)
- Study completion
- Sep 1, 2029 (estimated)
- Target enrollment
- 24 participants (estimated)
- Last updated on registry
- Sep 1, 2026
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- Massachusetts General Hospital
- Principal investigator
- Andrew R. Branagan, M.D., Ph.D., Principal Investigator
Massachusetts General Hospital - Collaborators
- Johnson & Johnson
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Andrew Branangan, MD, PhD 📞 617-724-4000 ✉ abranagan@mgh.harvard.edu
Participating sites (2)
- Massachusetts General Hospital
Boston, Massachusetts, 02114 · United States
- Andrew Branangan, MD, PhD · 617-724-4000 · abranagan@mgh.harvard.edu
- Andrew Branagan, MD, PhD
- Dana-Farber Cancer Institute
Boston, Massachusetts, 02115 · United States
- Tarek Mouhieddine, MD · 855-281-2811 · TAREK_MOUHIEDDINE@DFCI.HARVARD.EDU
- Tarek Mouhieddine, MD
Terms used on this page · explanations by MedicalUpdates.ai
- relapsed or refractory
- A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
- prior therapy
- Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
- contraindications
- A reason a particular test or treatment should not be used for a person, for example a metal implant that rules out an MRI scan.
- ECOG performance status
- A scale from 0 to 5 that describes how a person's condition affects daily activity. 0 means fully active; 1 means restricted in strenuous activity; 2 means able to self-care but unable to work; higher numbers mean more limitation.
- Karnofsky
- A scale from 100 (no complaints) down to 0 that describes how well a person can carry out daily activities. Studies often require a minimum score.
- childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- at screening
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- Absolute neutrophil count
- The number of neutrophils, a type of white blood cell that fights infection, in a blood sample. Studies often require it to be above a set level.
- ULN
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- Creatinine clearance
- A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
- written informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- investigational
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- immunosuppressant
- A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
- prednisone
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- Sponsor
- The organisation or person that initiates the study and has authority over it. The sponsor may be a company, hospital, university, government agency or individual, and is not necessarily the organisation that funds the study.
- complete remission
- No sign of the condition can be found with the tests used in the study. It does not always mean the condition is gone permanently, and the definition depends on the condition and the study.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- open label
- No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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