A Clinical Study of Zilovertamab Vedotin (MK-2140) Plus Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Polatuzumab Vedotin Plus R-CHP in People With Diffuse Large B-cell Lymphoma (DLBCL) (MK-2140-011/waveLINE-011)
- Conditions
- Lymphoma, Large B-Cell, Diffuse
- Interventions
- Registration Number
- NCT06890884
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 594
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.
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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP) Zilovertamab vedotin 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). 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). Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP) Rituximab 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). 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). Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP) Cyclophosphamide 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). 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). Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP) Doxorubicin 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). 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). Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP) Rituximab Biosimilar 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). 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). Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP) Prednisone 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). 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). Zilovertamab vedotin + Rituximab + Cyclophosphamide, Doxorubicin, Prednisone (R-CHP) Prednisolone 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). 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). Polatuzumab vedotin + R-CHP Doxorubicin 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). 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). Polatuzumab vedotin + R-CHP Rituximab 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). 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). Polatuzumab vedotin + R-CHP Cyclophosphamide 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). 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). Polatuzumab vedotin + R-CHP Rituximab Biosimilar 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). 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). Polatuzumab vedotin + R-CHP Prednisone 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). 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). Polatuzumab vedotin + R-CHP Prednisolone 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). 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). Polatuzumab vedotin + R-CHP Polatuzumab vedotin 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). 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).
- Primary Outcome Measures
Name Time Method Complete Response Rate (CRR) at End of Treatment (EOT) per Lugano Response Criteria Up to approximately 31 months CRR at EOT is defined as the percentage of participants who experience complete response (CR) per Lugano response criteria as assessed by blinded independent central review (BICR) at end of treatment. CR is complete metabolic (no/minimal FDG uptake) and radiologic response (target lesions regress to ≤1.5 cm in longest transverse diameter of a lesion) and no new lesions. Participants with missing data or who discontinue treatment or study prior to reaching EOT will be considered non-responders and included in the total number of participants.
- Secondary Outcome Measures
Name Time Method Number of participants who experience one or more adverse events (AEs) Up to approximately 9 months An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented.
Progression-free Survival (PFS) per Lugano Response Criteria Up to approximately 51 months PFS is defined as the time from randomization to the first documented disease progression per Lugano response criteria by BICR or death due to any cause, whichever occurs first.
Duration of CR Up to approximately 51 months For participants who demonstrate CR at EOT per Lugano response criteria by BICR, duration of complete response is defined as the time from the first documented evidence of CR at or before EOT until disease progression or death due to any cause, whichever occurs first.
Number of participants who discontinue study intervention due to an AE Up to approximately 6 months An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience at least one AE will be presented.
Overall Survival (OS) Up to approximately 87 months OS is defined as the time from randomization to death due to any cause.
Event-free Survival (EFS) per Lugano Response Criteria Up to approximately 51 months EFS is defined as the time from randomization to any of the following events: progressive disease per Lugano response criteria by BICR, death due to any cause, initiation of a new anti-caner therapy, or a positive biopsy for residual disease. The EFS for all participants will be presented.
Change From Baseline in Health-Related Quality Of Life (HRQoL) on Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Trial Outcome Index (TOI) Baseline and up to Week 25 The FACT-Lym is a 42-item questionnaire designed to measure HRQoL and cancer-specific symptoms in non-Hodgkin lymphoma patients. Subscales include FACT-General (FACT-G), FACT-Trial Outcome Index (FACT-TOI), FACT-Lym total score (FACT-Lym TS), and the Lymphoma subscale (Lym S). The Lym S has a single domain consisting of 15 items specific to lymphoma burden with a score ranging from 0 to 60. FACT-G has 4 well-being domains, physical (7 items), social/family (7), emotional (6), and functional (7), with scores ranging from 0 to 108. FACT-TOI combines FACT-G's physical and functional domains with Lym S, with scores ranging from 0 to 116. FACT-Lym TS combines FACT-G with Lym S, with scores ranging from 0 to 168. The scoring of FACT-Lym is on a 5-point Likert scale from 0 to 4, with 0= not at all, 1= a little bit, 2= somewhat, 3=quite a bit, 4=very much. The higher the score the better the quality of life.
Change From Baseline in HRQoL on FACT-Lym Total Score Baseline and up to Week 25 The FACT-Lym is a 42-item questionnaire designed to measure HRQoL and cancer-specific symptoms in non-Hodgkin lymphoma patients. Subscales include FACT-General (FACT-G), FACT-Trial Outcome Index (FACT-TOI), FACT-Lym total score (FACT-Lym TS), and the Lymphoma subscale (Lym S). The Lym S has a single domain consisting of 15 items specific to lymphoma burden with a score ranging from 0 to 60. FACT-G has 4 well-being domains, physical (7 items), social/family (7), emotional (6), and functional (7), with scores ranging from 0 to 108. FACT-TOI combines FACT-G's physical and functional domains with Lym S, with scores ranging from 0 to 116. FACT-Lym TS combines FACT-G with Lym S, with scores ranging from 0 to 168. The scoring of FACT-Lym is on a 5-point Likert scale from 0 to 4, with 0= not at all, 1= a little bit, 2= somewhat, 3=quite a bit, 4=very much. The higher the score the better the quality of life.
Change From Baseline in HRQoL on FACT-Lym Physical Well-being (PWB) (Items General Physical [GP]1 through GP7) Baseline and up to Week 25 The FACT-Lym is a 42-item questionnaire designed to measure HRQoL and cancer-specific symptoms in non-Hodgkin lymphoma patients. Subscales include FACT-General (FACT-G), FACT-Trial Outcome Index (FACT-TOI), FACT-Lym total score (FACT-Lym TS), and the Lymphoma subscale (Lym S). The Lym S has a single domain consisting of 15 items specific to lymphoma burden with a score ranging from 0 to 60. FACT-G has 4 well-being domains, physical (7 items), social/family (7), emotional (6), and functional (7), with scores ranging from 0 to 108. FACT-TOI combines FACT-G's physical and functional domains with Lym S, with scores ranging from 0 to 116. FACT-Lym TS combines FACT-G with Lym S, with scores ranging from 0 to 168. The scoring of FACT-Lym is on a 5-point Likert scale from 0 to 4, with 0= not at all, 1= a little bit, 2= somewhat, 3=quite a bit, 4=very much. The higher the score the better the quality of life.
Change From Baseline in HRQoL on Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) Neurotoxicity Subscale Score Baseline and up to Week 25 The FACT/GOG-NTX provides a targeted assessment of symptoms of peripheral neuropathy, including sensory, motor, and auditory problems and cold sensitivity. It is an 11-item questionnaire designed to measure the neurotoxicity subscale. The scoring of FACT/GOG-NTX is on a 5-point Likert scale from 0 to 4, with 0= not at all, 1= a little bit, 2= somewhat, 3=quite a bit, 4=very much. To produce a Neurotoxicity Subscale score (range 0-44), the sum of the item scores are multiplied by the number of items in the subscale, then divided by the number of items answered.
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Trial Locations
- Locations (2)
Haddasah Medical Center ( Site 0601)
🇮🇱Jerusalem, Israel
Sheba Medical Center ( Site 0603)
🇮🇱Ramat Gan, Israel