Purpose

Researchers are looking for ways to treat germinal center B-cell-like diffuse large B-cell lymphoma (GCB DLBCL). DLBCL is a fast-growing blood cancer that affects B-cells. GCB is a type of DLBCL that affects young B-cells that are still maturing. The goal of this study is to learn if more people who receive zilovertamab vedotin (MK-2140) and R-CHP have the cancer respond (go away) than those who receive polatuzumab vedotin and R-CHP.

Condition

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

Inclusion Criteria

The main inclusion criteria include but are not limited to the following: - Has histologically confirmed diagnosis of germinal center B-cell (GCB) subtype of diffuse large B-cell lymphoma (DLBCL), by prior biopsy, according to the World Health Organization (WHO) classification of neoplasms of the hematopoietic and lymphoid tissues. - Has positron emission tomography (PET) positive disease at screening, defined as 4 to 5 on the Lugano 5-point scale. - Has received no prior treatment for their DLBCL. - Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART). - Participants who are hepatitis B surface antigen (HBsAg) positive are eligible if they have received hepatitis B virus (HBV) antiviral therapy and have undetectable HBV viral load prior to randomization. - Participants with history of hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable at screening.

Exclusion Criteria

The main exclusion criteria include but are not limited to the following: - Has a history of transformation of indolent disease to DLBCL. - Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL) or Grey zone lymphoma. - Has Ann Arbor Stage I DLBCL. - Has clinically significant (i.e., active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to enrollment), myocardial infarction (<6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication. - Has clinically significant pericardial or pleural effusion. - Has ongoing Grade >1 peripheral neuropathy. - Has a demyelinating form of Charcot-Marie-Tooth disease. - HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease. - Has ongoing corticosteroid therapy. - Known additional malignancy that is progressing or has required active treatment within the past 2 years. - Known active central nervous system (CNS) lymphoma. - Has active autoimmune disease that has required systemic treatment in the past 2 years. - Has active infection requiring systemic therapy. - Has active HBV (defined as HBsAg positive and detectable HBV deoxyribonucleic acid (DNA)) and HCV (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid (RNA)) infection. - Has history of stem cell/solid organ transplant.

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP)
Participants will receive a dose of zilovertamab vedotin (1.75 mg/kg) plus 750 mg/m^2 cyclophosphamide, 50 mg/m^2 doxorubicin, and 375 mg/m^2 rituximab or rituximab biosimilar administered by intravenous (IV) infusion on Day 1 of each 3-week cycle for up to 6 cycles (up to approximately 4 months) plus 2 additional cycles of rituximab or biosimilar for participants with high risk DLBCL. Participants will also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 3-week cycle for up to 6 cycles (up to approximately 4 months).
  • Biological: Zilovertamab vedotin
    IV infusion
    Other names:
    • MK-2140
    • VLS-101
  • Biological: Rituximab
    IV infusion
    Other names:
    • RITUXAN®
  • Drug: Cyclophosphamide
    IV infusion
    Other names:
    • CYTOXAN®
    • NEOSAR®
  • Drug: Doxorubicin
    IV infusion
    Other names:
    • ADRIAMYCIN®
  • Biological: Rituximab Biosimilar
    IV infusion
    Other names:
    • TRUXIMA®
    • RUXIENCE®
    • RIABNI®
  • Drug: Prednisone
    Oral administration or IV infusion
  • Drug: Prednisolone
    Oral administration or IV infusion
  • Drug: Rescue Medication
    Participants receive rescue medication at the investigators discretion, per approved product label. Recommended rescue medication is Granulocyte Colony-Stimulating Factor (G-CSF).
Active Comparator
Polatuzumab vedotin + R-CHP
Participants will receive a dose of polatuzumab vedotin (1.8 mg/kg) plus 750 mg/m^2 cyclophosphamide, 50 mg/m^2 doxorubicin, and 375 mg/m^2 rituximab or rituximab biosimilar administered by IV infusion on Day 1 of each 3-week cycle for up to 6 cycles (up to approximately 4 months) plus 2 additional cycles of rituximab or biosimilar for participants with high risk DLBCL. Participants will also receive 100 mg prednisone or prednisolone via oral tablet per day during Days 1-5 of each 3-week cycle for up to 6 cycles (up to approximately 4 months).
  • Biological: Rituximab
    IV infusion
    Other names:
    • RITUXAN®
  • Drug: Cyclophosphamide
    IV infusion
    Other names:
    • CYTOXAN®
    • NEOSAR®
  • Drug: Doxorubicin
    IV infusion
    Other names:
    • ADRIAMYCIN®
  • Biological: Rituximab Biosimilar
    IV infusion
    Other names:
    • TRUXIMA®
    • RUXIENCE®
    • RIABNI®
  • Drug: Prednisone
    Oral administration or IV infusion
  • Drug: Prednisolone
    Oral administration or IV infusion
  • Biological: Polatuzumab vedotin
    IV infusion
  • Drug: Rescue Medication
    Participants receive rescue medication at the investigators discretion, per approved product label. Recommended rescue medication is Granulocyte Colony-Stimulating Factor (G-CSF).

Recruiting Locations

Georgetown University Medical Center ( Site 0117)
Washington D.C. 4140963, District of Columbia 4138106 20007
Contact:
Study Coordinator
202-444-2223

More Details

Status
Recruiting
Sponsor
Merck Sharp & Dohme LLC

Study Contact

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

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.