Loncastuximab Tesirine in WM

NCT05190705 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 21-622
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 4

Brief 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

Conditions

Waldenstrom Macroglobulinemia

Keywords

Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (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).

  4 weeks up to 6 months

Secondary Outcomes (15)

• Number of Participants With Complete Response

  6 months

• Number of Participants With Very Good Partial Response

  6 months

• Number of Participants With Partial Response

  6 months

• Number of Participants With Minor Response

  6 months

• Number of Participants With Stable Disease

  6 months

Study Arms (1)

Loncastuximab Tesirine + Dexamethasone

EXPERIMENTAL

Participants 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

Drug: Loncastuximab Tesirine; Drug: Dexamethasone

Interventions

Loncastuximab Tesirine DRUG

Administered by intravenous infusion

Also known as: Zynlonta

Loncastuximab Tesirine + Dexamethasone

Dexamethasone DRUG

Taken orally or administered by intravenous infusion

Also known as: Decadron, Dexamethasone Intensol, Dexpak, Taperpak

Loncastuximab Tesirine + Dexamethasone

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 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)
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Shayna Sarosiek, MD: lead
• ADC Therapeutics S.A.: collaborator

Study Sites (4)

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

RECRUITING

Fred Hutch

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Waldenstrom Macroglobulinemia

Interventions

loncastuximab tesirine; Dexamethasone; Calcium Dobesilate

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

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Shayna Sarosiek, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shayna Sarosiek, MD

CONTACT

617-632-6092; Shayna_sarosiek@dfci.harvard.edu

Kirsten Meid

CONTACT

kirsten_meid@dfci.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: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 29, 2021
• First Posted: January 13, 2022
• Study Start: February 17, 2022
• Primary Completion: May 1, 2026
• Study Completion (Estimated): August 1, 2028
• Last Updated: May 23, 2025

Record last verified: 2025-05

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 Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (4)