Clinical trial NCT05190705: Loncastuximab Tesirine in WM
Official title: A Phase II Study Evaluating Loncastuximab Tesirine in Patients With Previously Treated Waldenström Macroglobulinemia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Waldenstrom Macroglobulinemia
Keywords: Waldenstrom Macroglobulinemia
Lead sponsor: Dana-Farber Cancer Institute
Sponsor class: OTHER
Collaborators: name: ADC Therapeutics S.A.
First posted: 2022-01-13
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Overall Response Rate
timeFrame: 4 weeks up to 6 months
Secondary outcomes:
measure: Number of Participants With Complete Response
timeFrame: 6 months
measure: Number of Participants With Very Good Partial Response
timeFrame: 6 months
measure: Number of Participants With Partial Response
timeFrame: 6 months
measure: Number of Participants With Minor Response
timeFrame: 6 months
measure: Number of Participants With Stable Disease
timeFrame: 6 months
measure: Progression Free Survival
timeFrame: 3 years
measure: Bone marrow response
timeFrame: 6 months
measure: Overall Response Rate Among Participants Without MYD88 Mutations
timeFrame: 6 months
measure: Overall Response Rate Among Participants Without CXCR4 Mutations
timeFrame: 6 months
measure: Number of Participants With Treatment-related Adverse Events
timeFrame: 6 months
measure: Number of Participants With IgM Flare
timeFrame: 6 months
measure: Number of Participants With Tumor Lysis Syndrome
timeFrame: 6 months
measure: Impact of loncastuximab tesirine in the participants' quality of life
timeFrame: 6 months
measure: Overall Response Rate Among CXCR4 Mutated Participants
timeFrame: 6 months
measure: Overall Response Rate Among Participants With MYD88 Mutations
timeFrame: 6 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Seattle
country: United States
facility: Fred Hutch
state: Washington
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Shayna Sarosiek, MD
role: PRINCIPAL_INVESTIGATOR
References: