NCT06717347 - A Study to Evaluate Zilovertamab Vedotin (MK-2140) Combination With Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Previously Untreated DLBCL (MK-2140-010) | Crick

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Has histologically confirmed diagnosis of diffuse large B-cell lymphoma (DLBCL), by prior biopsy, based on local testing according to the 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 * Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 assessed within 7 days before randomization * Has an ejection fraction ≥45% as determined by either echocardiogram (ECHO) or multigated acquisition (MUGA) * Human immunodeficiency virus (HIV) infected participants must have well controlled HIV on antiretroviral therapy (ART) * 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: * 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 * Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed * 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 concurrent active HBV (defined as HBsAg positive and detectable HBV DNA) and HCV (defined as anti-HCV antibody positive and detectable HCV ribonucleic acid (RNA)) infection * Has history of allogeneic tissue/solid organ transplant

Outcomes

Primary Outcomes

Progression-free survival (PFS)

PFS is defined as the time from randomization to the first documented disease progression per Lugano response criteria by blinded independent central review (BICR) or death due to any cause, whichever occurs first.

Time frame: Up to ~ 50 months

Secondary Outcomes

Complete Response at End of Treatment (CR at EOT)

CR at EOT is defined as a CR per Lugano response criteria as assessed by BICR at end of treatment. 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.

Time frame: Up to ~ 32 months

Overall Survival (OS)

OS is defined as the time from randomization to death due to any cause.

Time frame: Up to ~ 74 months

Event-free Survival (EFS)

EFS is defined as the time from randomization to any of the following events: progressive disease that precludes surgery, local or distant recurrence, second primary malignancy or death due to any cause. The EFS for all participants will be presented.

Time frame: Up to ~ 74 months

Duration of Complete Response (DurCR)

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.

Time frame: Up to ~ 74 months

Number of Participants Who Experience an Adverse Event (AE)

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.

Time frame: Up to ~ 9 months

Number of Participants Who Discontinue Study Treatment Due to an AE

Time frame: Up to ~ 6 months

Change From Baseline in Health-Related Quality Of Life (HRQoL) on Functional Assessment of Cancer Therapy Lymphoma (FACT-Lym) Trial Outcome Index (TOI) Score

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.

Time frame: Baseline and Week 25

Change From Baseline in HRQoL on FACT-Lym Total Score

Time frame: Baseline and Week 25

Change From Baseline in HRQoL on FACT-Lym Physical Wellbeing (PWB) Score

Time frame: Baseline and Week 25

Change From Baseline in HRQoL on Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX) Neurotoxicity Subscale Score

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), multiply the sum of the item scores by the number of items in the subscale, then divide by the number of items answered.

Time frame: Baseline and Week 25

A Study to Evaluate Zilovertamab Vedotin (MK-2140) Combination With Rituximab Plus Cyclophosphamide, Doxorubicin, and Prednisone (R-CHP) Versus Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (R-CHOP) in Participants With Previously Untreated DLBCL (MK-2140-010)

Overview

Conditions

Interventions

Eligibility

Locations (278)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts