Brief Title
Loncastuximab Tesirine in WM
Official Title
A Phase II Study Evaluating Loncastuximab Tesirine in Patients With Previously Treated Waldenström Macroglobulinemia
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
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
Overall Response Rate
Secondary Outcome
Number of Participants With Complete Response
Condition
Waldenstrom Macroglobulinemia
Intervention
Loncastuximab Tesirine
Study Arms / Comparison Groups
Loncastuximab Tesirine + Dexamethasone
Description: 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
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
36
Start Date
February 17, 2022
Completion Date
August 1, 2027
Primary Completion Date
May 1, 2023
Eligibility Criteria
Inclusion Criteria:
- 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
- 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 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.
- 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.
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Shayna Sarosiek, MD, 617-632-6092, [email protected]
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT05190705
Organization ID
21-622
Responsible Party
Sponsor-Investigator
Study Sponsor
Shayna Sarosiek, MD
Collaborators
ADC Therapeutics S.A.
Study Sponsor
Shayna Sarosiek, MD, Principal Investigator, Dana-Farber Cancer Institute
Verification Date
November 2022