RECRUITING

A Study of Zilovertamab Vedotin (MK-2140) as Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (MK-2140-006)

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The purpose of this study is to assess the safety and tolerability of zilovertamab vedotin as monotherapy and in combination in participants with select B-cell lymphomas including mantle cell lymphoma (MCL), Richter's transformation lymphoma (RTL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). This study will also evaluate zilovertamab vedotin as monotherapy and in combination with respect to objective response rate. * Cohort A: Participants with relapsed or refractory MCL relapsed or refractory disease after at least 2 prior systemic therapies including a Bruton's tyrosine kinase inhibition/inhibitor (BTKi), and post therapy chimeric antigen receptor T (CAR-T) cell therapy or ineligible for CAR-T cell therapy * Cohort B: Participants with relapsed or refractory RT disease after at least 1 prior systemic therapy * Cohort C: Participants with relapsed or refractory MCL relapsed or refractory disease after at least 1 prior systemic therapy and no prior exposure to a non-covalent BTKi * Cohort D: Participants with relapsed or refractory FL and CLL relapsed or refractory disease after at least 2 prior systemic therapies and have no other available therapy * Cohort E: Participants with relapsed or refractory FL after at least 2 prior systemic therapies and have no other available therapy The primary study hypothesis is that zilovertamab vedotin monotherapy has an increased Objective Response Rate (ORR) per Lugano Response Criteria as assessed by blinded independent central review (BICR). As of Amendment 07, Cohort D is closed to enrollment of participants with CLL and enrollment of participants into Arm 2 (zilovertamab vedotin at Dose 2 on Days 1 \& 8 of each 3 Week Cycle (Q2/3W)).

Official Title

A Multicenter, Open-label, Phase 2 Basket Study to Evaluate the Safety and Efficacy of MK-2140 as a Monotherapy and in Combination in Participants With Aggressive and Indolent B-cell Malignancies (waveLINE-006)

Quick Facts

Study Start:2022-07-21
Study Completion:2027-04-26
Study Type:Not specified
Phase:Not Applicable
Enrollment:Not specified
Status:RECRUITING

Study ID

NCT05458297

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years
Sexes Eligible for Study:ALL
Accepts Healthy Volunteers:No
Standard Ages:ADULT, OLDER_ADULT
Inclusion CriteriaExclusion Criteria
  1. * For aggressive B-cell malignancies mantle cell lymphoma (MCL): Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 2 prior systemic therapies including a Bruton's tyrosine kinase inhibition/inhibitor(s) (BTKi), and is post chimeric antigen receptor T (CAR-T) cell therapy or is ineligible for CAR-T cell therapy.
  2. * For aggressive B-cell malignancies MCL Cohort C: Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease after at least 1 prior systemic therapy and has no prior exposure to a non-covalent BTKi.
  3. * For aggressive B-cell malignancies Richter transformation lymphoma (RTL): Has histologically confirmed biopsy according to the 2016 World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues and has relapsed or refractory disease.
  4. * For indolent B-cell malignancies follicular lymphoma (FL) and chronic lymphocytic leukemia (CLL): Has histologically confirmed biopsy and has relapsed or refractory disease after at least 2 prior systemic therapies and no other available therapy.
  5. * Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy for at least 4 weeks and have undetectable HBV viral load prior to randomization/allocation.
  6. * Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before cycle 1 day 1.
  1. * Has received solid organ transplant at any time.
  2. * Has clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (\<6 months prior to enrollment), myocardial infarction (\<6 months prior to enrollment), unstable angina (\<6 months prior to enrollment), congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication.
  3. * Has pericardial effusion or clinically significant pleural effusion.
  4. * Has ongoing Grade \>1 peripheral neuropathy.
  5. * Has a demyelinating form of Charcot-Marie-Tooth disease.
  6. * Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
  7. * Participants with FL who have transformed to a more aggressive type of lymphoma.
  8. * Has received prior systemic anticancer therapy within 5 half-lives or 4 weeks (if prior therapy was a monoclonal antibodies) or 2 weeks (if prior therapy was small molecules like kinase inhibitors) prior to the first dose of study intervention.
  9. * Has received prior radiotherapy within 28 days of start of study intervention. Participants must have recovered from all radiation-related toxicities.
  10. * Has ongoing corticosteroid therapy exceeding 30 mg daily of prednisone equivalent.
  11. * Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
  12. * Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma.
  13. * Has an active infection requiring systemic therapy.
  14. * Has a known history of human immunodeficiency virus (HIV) infection.
  15. * Active HBV or hepatitis C virus (HCV) infection.
  16. * For Cohort C only: has any clinically significant gastrointestinal abnormalities that might alter absorption.

Contacts and Locations

Study Contact

Toll Free Number
CONTACT
1-888-577-8839
Trialsites@msd.com

Principal Investigator

Medical Director
STUDY_DIRECTOR
Merck Sharp & Dohme LLC

Study Locations (Sites)

Alaska Oncology and Hematology ( Site 0037)
Anchorage, Alaska, 99508
United States
Banner MD Anderson Cancer Center ( Site 0040)
Gilbert, Arizona, 85234
United States
Banner MD Anderson Cancer Center - University Medical Center Phoenix-Medical Oncology ( Site 0036)
Phoenix, Arizona, 85006
United States
University of Colorado Anschutz Medical Campus-The Center for Cancer and Blood Disorders ( Site 0008
Aurora, Colorado, 80045
United States
Cancer Care Specialists of Illinois ( Site 0031)
Decatur, Illinois, 62526
United States
University of Kansas Medical Center-Division of Hematologic Malignancies and Cellular Therapeutics (
Fairway, Kansas, 66205
United States
Norton Women's and Children's Hospital-Norton Cancer Institute - St. Matthews ( Site 0007)
Saint Matthews, Kentucky, 40207
United States
Greenebaum Comprehensive Cancer Center-Hematology & Multiple Myeloma ( Site 0010)
Baltimore, Maryland, 21201
United States
Tufts Medical Center ( Site 0024)
Boston, Massachusetts, 02111
United States
Massachusetts General Hospital ( Site 0018)
Boston, Massachusetts, 02114
United States
Dana-Farber Cancer Institute-Lymphoma ( Site 0026)
Boston, Massachusetts, 02215
United States
University of Michigan ( Site 0009)
Ann Arbor, Michigan, 48109
United States
Henry Ford Hospital ( Site 0035)
Detroit, Michigan, 48202
United States
Icahn School of Medicine at Mount Sinai ( Site 0023)
New York, New York, 10029
United States
Sanford Fargo Medical Center-Roger Maris Cancer Center ( Site 0014)
Fargo, North Dakota, 58122
United States
The James Cancer Hospital and Solove Research Institute at The Ohio State University Comprehensive C
Columbus, Ohio, 43210
United States
Avera Cancer Institute- Research ( Site 0011)
Sioux Falls, South Dakota, 57105
United States
Medical Oncology Associates, PS ( Site 0005)
Spokane, Washington, 99208
United States
University of Wisconsin Hospitals and Clinics-Carbone Cancer Center ( Site 0030)
Madison, Wisconsin, 53792
United States
MEDICAL COLLEGE OF WISCONSIN ( Site 0021)
Milwaukee, Wisconsin, 53226
United States

Collaborators and Investigators

Sponsor: Merck Sharp & Dohme LLC

  • Medical Director, STUDY_DIRECTOR, Merck Sharp & Dohme LLC

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2022-07-21
Study Completion Date2027-04-26

Study Record Updates

Study Start Date2022-07-21
Study Completion Date2027-04-26

Terms related to this study

Additional Relevant MeSH Terms

  • Chronic Lymphocytic Leukemia
  • Mantle Cell Lymphoma
  • Follicular Lymphoma
  • Richter Transformation Lymphoma