A Study of Zilovertamab Vedotin (MK-2140) in Combination With Cyclophosphamide, Doxorubicin, and Prednisone Plus Rituximab or Rituximab Biosimilar (Truxima) (R-CHP) in Participants With Diffuse Large B-Cell Lymphoma (DLBCL) (MK-2140-007)

NCT ID: NCT05406401

Last Updated: 2024-10-15

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-14

Study Completion Date

2029-04-26

Brief Summary

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This study consists of a dose escalation/confirmation phase and an efficacy expansion phase. The dose escalation/confirmation phase is to determine the safety and tolerability and establish a preliminary recommended Phase 2 dose (RP2D) of zilovertamab vedotin when administered in combination with R-CHP in participants with DLBCL who have received no prior treatment for their disease. The efficacy expansion phase is to determine the efficacy of the RP2D of zilovertamab vedotin when administered in combination with R-CHP in participants with DLBCL who have received no prior treatment for their disease.

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Detailed Description

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Conditions

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Lymphoma, Large B-Cell, Diffuse (DLBCL)

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Zilovertamab Vedotin + R-CHP: Dose Escalation/Confirmation

Participants in the dose escalation/confirmation phase receive a dose level of zilovertamab vedotin (from 1.5 mg/Kg up to 2.5 mg/Kg) plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months).

Group Type EXPERIMENTAL

Zilovertamab Vedotin

Intervention Type BIOLOGICAL

IV infusion

Cyclophosphamide

Intervention Type DRUG

IV infusion

Doxorubicin

Intervention Type DRUG

IV infusion

Rituximab

Intervention Type BIOLOGICAL

IV infusion

Rituximab Biosimilar

Intervention Type BIOLOGICAL

IV infusion

Prednisone

Intervention Type DRUG

IV or oral administration (per local guidelines)

Prednisolone

Intervention Type DRUG

IV or oral administration (per local guidelines)

Zilovertamab Vedotin + R-CHP: Efficacy Expansion

Participants in the efficacy expansion phase receive the RP2D of zilovertamab vedotin plus 750 mg/m\^2 cyclophosphamide, 50 mg/m\^2 doxorubicin, and 375 mg/m\^2 rituximab or rituximab biosimilar (truxima) administered by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for up to 8 cycles (up to approximately 5.5 months). Participants also receive 100 mg prednisone or prednisolone per day during Days 1-5 of each 21-day cycle for up to 8 cycles (up to approximately 5.5 months).

Group Type EXPERIMENTAL

Zilovertamab Vedotin

Intervention Type BIOLOGICAL

IV infusion

Cyclophosphamide

Intervention Type DRUG

IV infusion

Doxorubicin

Intervention Type DRUG

IV infusion

Rituximab

Intervention Type BIOLOGICAL

IV infusion

Rituximab Biosimilar

Intervention Type BIOLOGICAL

IV infusion

Prednisone

Intervention Type DRUG

IV or oral administration (per local guidelines)

Prednisolone

Intervention Type DRUG

IV or oral administration (per local guidelines)

Interventions

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Zilovertamab Vedotin

IV infusion

Intervention Type BIOLOGICAL

Cyclophosphamide

IV infusion

Intervention Type DRUG

Doxorubicin

IV infusion

Intervention Type DRUG

Rituximab

IV infusion

Intervention Type BIOLOGICAL

Rituximab Biosimilar

IV infusion

Intervention Type BIOLOGICAL

Prednisone

IV or oral administration (per local guidelines)

Intervention Type DRUG

Prednisolone

IV or oral administration (per local guidelines)

Intervention Type DRUG

Other Intervention Names

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MK-2140 VLS-101 CYTOXAN® NEOSAR® ADRIAMYCIN® RITUXAN® TRUXIMA®

Eligibility Criteria

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Exclusion Criteria

Inclusion:

* Has histologically confirmed diagnosis of DLBCL by prior biopsy
* Has PET-positive disease verified by blinded independent central review (BICR) at screening, defined as 4-5 on the Lugano response criteria 5-point scale
* Has received no prior treatment for DLBCL
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed within 7 days prior to the start of study intervention

Exclusion:

* Has a history of transformation of indolent disease to DLBCL
* Has received solid organ transplant at any time
* Has received a diagnosis of primary mediastinal B-cell lymphoma (PMBCL)
* 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, congestive heart failure (New York Heart Association Classification Class ≥II), or serious cardiac arrhythmia requiring medication
* Has pericardial effusion or clinically significant pleural effusion
* Has ongoing Grade \>1 peripheral neuropathy
* Has a demyelinating form of Charcot-Marie-Tooth disease
* History of a second malignancy unless potentially curative treatment has been completed with no evidence of malignancy for 2 years with the exception of participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous-cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder
* Has received prior radiotherapy within 28 days of start of study intervention
* Has ongoing corticosteroid therapy (exceeding 30 mg daily of prednisone equivalent)
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
* Has received a strong inhibitor or inducer of CYP3A4 (including itraconazole, ketoconazole, posaconazole, or voriconazole) within 7 days prior to the start of study intervention or expected requirement for chronic use of a strong CYP3A4 inhibitor until \<30 days after the last dose
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 28 days before the first dose of study intervention
* Has known active central nervous system (CNS) lymphoma
* Has an active infection requiring systemic therapy
* Has a known history of human immunodeficiency virus (HIV) infection
* Has a known active hepatitis C virus infection
* Has a known active hepatitis B virus infection
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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BC Cancer Victoria-Clinical Trials Unit ( Site 0105)

Victoria, British Columbia, Canada

Site Status

William Osler Health System ( Site 0106)

Toronto, Ontario, Canada

Site Status

Hopital du Sacre-Coeur de Montreal ( Site 0108)

Montreal, Quebec, Canada

Site Status

Hadassah Medical Center ( Site 0401)

Jerusalem, , Israel

Site Status

Sheba Medical Center-Hemato Oncology ( Site 0400)

Ramat Gan, , Israel

Site Status

Fondazione Policlinico Universitario Agostino Gemelli-ISTITUTO DI EMATOLOGIA ( Site 0306)

Rome, Lazio, Italy

Site Status

Ospedale San Raffaele-Unità Linfomi ( Site 0305)

Milan, Lombardy, Italy

Site Status

Az. Osp. Ospedali Riuniti VILLA SOFIA-CERVELLO-EMATOLOGIA I ( Site 0307)

Palermo, Sicily, Italy

Site Status

Azienda Ospedaliera Universitaria Careggi-SOD Ematologia ( Site 0308)

Florence, Tuscany, Italy

Site Status

Azienda Ospedaliera Nazionale SS. Antonio e Biagio e Cesare -Azienda Ospedaliera Nazionale SS. Ant

Alessandria, , Italy

Site Status

Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - P-Kilinka Onkologii I Hematologii ( Site

Warsaw, Masovian Voivodeship, Poland

Site Status

Uniwersyteckie Centrum Kliniczne-Klinika Hematologii i Transplantologii ( Site 0504)

Gdansk, Pomeranian Voivodeship, Poland

Site Status

Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0505)

Gliwice, Silesian Voivodeship, Poland

Site Status

Wojewodzkie Wielospecjalistyczne Centrum Onkologii i Traumat-Oddiał Hematologii Ogólnej ( Site 0503)

Lodz, Łódź Voivodeship, Poland

Site Status

Seoul National University Hospital ( Site 0201)

Seoul, , South Korea

Site Status

Samsung Medical Center ( Site 0200)

Seoul, , South Korea

Site Status

HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Hematology ( Site 0704)

Seville, Andalusia, Spain

Site Status

Instituto Catalan de Oncologia - Hospital Duran i Reynals-Haematology Department ( Site 0703)

L'Hospitalet Del Llobregat, Barcelona, Spain

Site Status

Hospital Universitario Fundación Jiménez Díaz-Oncology & Hematology ( Site 0700)

Madrid, , Spain

Site Status

Mega Medipol-Hematology ( Site 0808)

Stanbul, Istanbul, Turkey (Türkiye)

Site Status

Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 0801)

Ankara, , Turkey (Türkiye)

Site Status

Trakya University ( Site 0805)

Edirne, , Turkey (Türkiye)

Site Status

Countries

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Canada Israel Italy Poland South Korea Spain Turkey (Türkiye)

Related Links

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Other Identifiers

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MK-2140-007

Identifier Type: OTHER

Identifier Source: secondary_id

2022-501380-40

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1280-2348

Identifier Type: OTHER

Identifier Source: secondary_id

2021-005861-41

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

2140-007

Identifier Type: -

Identifier Source: org_study_id

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