Loncastuximab Tesirine for the Treatment of Previously Treated Waldenstrom Macroglobulinemia
This phase II trial tests whether loncastuximab tesirine works in treating patients with Waldenstrom macroglobulinemia. Loncastuximab tesirine is a type of therapy called an antibody drug conjugate. Loncastuximab tesirine is a monoclonal antibody, called loncastuximab, linked to a drug, called pyrrolobenzodiazepine (PBD). Loncastuximab is a form of targeted therapy because it attaches to specific molecules (receptors) on the surface of cancer cells, known as CD19 receptors, and delivers PBD to kill them.
Inclusion Criteria
- Clinicopathological diagnosis of Waldenstrom macroglobulinemia
- Symptomatic disease meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenstrom macroglobulinemia
- At least 2 prior lines of treatment, including an anti-CD20 monoclonal antibody- containing regimen and a Bruton's tyrosine kinase (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
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%)
- 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 10 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 7 months after discontinuation from the study
- Absolute neutrophil count >= 1000/ uL. Growth factors are not permitted =< 14 days prior to cycle 1 day 1 (C1D1)
- Platelets >= 50,000/ uL. Platelet transfusions are not permitted =< 14 days prior to C1D1
- Hemoglobin >= 7 g/dL. Red blood cell (RBC) transfusions are not permitted =< 14 days prior to C1D1
- Total bilirubin =< 1.5 X upper limit of normal (ULN), or =< 3 x ULN with documented liver metastases and/or Gilbert’s Disease
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x 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
Exclusion Criteria
- 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 central nervous system (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., hepatitis B surface antigen negative [HBs Ag-], and hepatitis B surface antibody positive [anti- HBs+] and hepatitis C antibody negative [anti-HBC-]) and positive hepatitis B core antibody (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
- 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, electrocardiogram (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
Additional locations may be listed on ClinicalTrials.gov for NCT05190705.
Locations matching your search criteria
United States
Massachusetts
Boston
Minnesota
Rochester
Washington
Seattle
PRIMARY OBJECTIVE:
I. To evaluate the rate of very good partial response or better to loncastuximab tesirine in patients with previously treated Waldenstrom macroglobulinemia (WM).
SECONDARY OBJECTIVES:
I. To evaluate the rates of complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD) and progressive disease (PD) to loncastuximab tesirine in patients with previously treated WM.
II. To evaluate progression free survival (PFS) with loncastuximab tesirine in patients with previously treated WM.
III. To evaluate the effect in bone marrow burden of disease with loncastuximab tesirine treatment.
IV. To evaluate the impact of MYD88 and CXCR4 mutations on response to loncastuximab tesirine.
V. To evaluate the safety profile of loncastuximab tesirine in patients with WM.
VI.To evaluate the rate of IgM flare during treatment of WM with loncastuximab tesirine.
VII.To evaluate the rate of tumor lysis syndrome during treatment of WM with loncastuximab tesirine.
VIII. To evaluate quality of life changes based on the Quality of Life Questionnaire (QLQ)-30 (European Organization for Research and Treatment of Cancer [EORTC]) during treatment with loncastuximab tesirine.
OUTLINE:
Patients receive loncastuximab tesirine intravenously (IV) over 30 minutes on day 1. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT scan, bone marrow biopsy and aspiration and blood sample collection throughout the study.
After completion of study treatment, patients are followed every 12 weeks until they start a new therapy or death.
Trial PhasePhase II
Trial Typetreatment
Lead OrganizationDana-Farber Harvard Cancer Center
Principal InvestigatorShayna Sarosiek
- Primary ID21-622
- Secondary IDsNCI-2022-01727
- ClinicalTrials.gov IDNCT05190705