Teclistamab In Waldenstrom's Macroglobulinemia

NCT07791498 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 26-302
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Waldenstrom's Macroglobulinemia

Keywords

relapsed; refractory; waldenstrom's macroglobulinemia; teclistamab; WM

Outcome Measures

Primary Outcomes (1)

• Overall Immunoglobulin M Response in Relapsed or Refractory Participants with Waldenstrom's Macroglobulinemia

  Overall immunoglobulin M (IgM) efficacy will be evaluated by assessing the IgM response rate and the objective response rate (ORR, PR or better; at least 25% improvement in IgM from baseline). Overall response rate (ORR) includes patients who achieved minor response (MR), partial response (PR), very good partial response (VGPR), and complete response (CR). Response rates will be presented with exact 95% confidence intervals. With 24 patients, there is 99% power to reject a null rate of IgM response of 0.30 assuming an alternative IgM response rate of 0.70 based on the exact binomial exact test with a one-sided significance level of 0.03. The alternative IgM response rate will be rejected if at least 12 of 24 patients have a response.

  Day 1 of cycle 1 to first documentation of ORR, PR or better up to 3 years from the last treatment date.

Secondary Outcomes (7)

• Safety and Tolerability of Teclistamab

  Day 1 of cycle 1 to end of follow-up phase, up to 3 years from the last treatment date.

• Immunoglobulin M Major Response Rate

  Day 1 of cycle 1 to first documentation of PR, VDPR, and/or CR up to 3 years from the last treatment date.

• Median Time to Response

  Day 1 of cycle 1 to first documentation of any response up to 3 years after last treatment date.

• Median Time to Major Response

  Day 1 of cycle 1 to first documentation of major response up to 3 years from last treatment date.

• Progression-Free Survival

  Day 1 of cycle 1 to first documentation of disease progression, initiation of new therapy, or death, whichever occurs first, up to 3 years from the last treatment date.

Study Arms (1)

Teclistamab

EXPERIMENTAL

Participants with relapsed or refractory Waldenstrom's macroglobulinemia will receive teclistamab. Teclistamab will be administered at the pre-determined dose on days 1, 4, and 7 of the first 14-day cycle via subcutaneous injection into their abdomen. Then, participants will be given teclistamab once every week for up to four 28-day cycles, and then for up to four 56-day cycles, with a maximum of 9 cycles.

Drug: Teclistamab

Interventions

Teclistamab DRUG

Subcutaneous injection into the abdomen received on days 1, 4, and 7 of the first 14-day cycle, then every week for up to four 28-day cycles, and then for up to four 56-day cycles, with a maximum of 9 cycles.

Teclistamab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Johnson & Johnson: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Andrew Branagan, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew Branangan, MD, PhD

CONTACT

617-724-4000; abranagan@mgh.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 24, 2026
• First Posted: August 28, 2026
• Study Start (Estimated): February 19, 2027
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2029
• Last Updated: August 28, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data can be shared no earlier than 1 year following the date of publication.
• Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation

Locations

US (2)