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Lymphoma, Large B-Cell, Diffuse (DLBCL)Phase 2waveLINE-007NCT05406401

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)

A Phase 2 study testing Zilovertamab Vedotin, Cyclophosphamide and Doxorubicin in people with Lymphoma, Large B-Cell, Diffuse (DLBCL), run by Merck Sharp & Dohme LLC at 22 sites in 7 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Large B-Cell, Diffuse (DLBCL)
What is being tested?
Zilovertamab Vedotin, Cyclophosphamide and Doxorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
22 sitesin 7 countries
Study dates
14 Jul 2022to 26 Apr 2029
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 18Show fewer
  • 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

Trial locations and contacts

22 sites in 7 countries.

22 sites in 7 countries

Italy5 sites

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

    Alessandria, 15121

  • Azienda Ospedaliera Universitaria Careggi-SOD Ematologia ( Site 0308)

    Florence, Tuscany, 50134

  • Ospedale San Raffaele-Unità Linfomi ( Site 0305)

    Milan, Lombardy, 20132

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

    Palermo, Sicily, 90146

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

    Rome, Lazio, 00168

Other trials in Italy

Poland4 sites

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

    Gdansk, Pomeranian Voivodeship, 80-214

  • Narodowy Instytut Onkologii - Oddzial w Gliwicach ( Site 0505)

    Gliwice, Silesian Voivodeship, 44-101

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

    Lodz, Łódź Voivodeship, 93-513

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

    Warsaw, Masovian Voivodeship, 02-781

Other trials in Poland

Canada3 sites

  • Hopital du Sacre-Coeur de Montreal ( Site 0108)

    Montreal, Quebec, H4J 1C5

  • William Osler Health System ( Site 0106)

    Toronto, Ontario, L6R3J7

  • BC Cancer Victoria-Clinical Trials Unit ( Site 0105)

    Victoria, British Columbia, V8R 6V5

Other trials in Canada

Spain3 sites

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

    L'Hospitalet Del Llobregat, Barcelona, 08908

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

    Madrid, 28040

  • HOSPITAL UNIVERSITARIO VIRGEN DEL ROCIO-Hematology ( Site 0704)

    Seville, Andalusia, 41013

Other trials in Spain

Turkey (Türkiye)3 sites

  • Ankara Universitesi Tip Fakultesi Hastanesi-hematology ( Site 0801)

    Ankara, 06620

  • Trakya University ( Site 0805)

    Edirne, 22030

  • Mega Medipol-Hematology ( Site 0808)

    Stanbul, Istanbul, 34214

Other trials in Turkey (Türkiye)

Israel2 sites

  • Hadassah Medical Center ( Site 0401)

    Jerusalem, 9112001

  • Sheba Medical Center-Hemato Oncology ( Site 0400)

    Ramat Gan, 5265601

Other trials in Israel

South Korea2 sites

  • Seoul National University Hospital ( Site 0201)

    Seoul, 03080

  • Samsung Medical Center ( Site 0200)

    Seoul, 06351

Other trials in South Korea

About this study

Official title: A Multicenter, Open-label, Phase 2 Dose Escalation and Confirmation, and Efficacy Expansion Study of Zilovertamab Vedotin (MK-2140) in Combination With R-CHP in Participants With DLBCL (waveLINE)

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.

Being tested
Zilovertamab Vedotin, Cyclophosphamide, Doxorubicin, Rituximab, Rituximab Biosimilar
Medical subject headings
Lymphoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Zilovertamab VedotinBiological

    Also called MK-2140, VLS-101

    IV infusion

  • CyclophosphamideDrug

    Also called CYTOXAN®, NEOSAR®

    IV infusion

  • DoxorubicinDrug

    Also called ADRIAMYCIN®

    IV infusion

  • RituximabBiological

    Also called RITUXAN®

    IV infusion

  • Rituximab BiosimilarBiological

    Also called TRUXIMA®

    IV infusion

  • PrednisoneDrug

    IV or oral administration (per local guidelines)

  • PrednisoloneDrug

    IV or oral administration (per local guidelines)

Study groups in NCT05406401
Study groupRoleWhat they receive
Zilovertamab Vedotin + R-CHP: Dose Escalation/ConfirmationExperimentalParticipants 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).
Receives: Biological: Zilovertamab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin; Biological: Rituximab; Biological: Rituximab Biosimilar; Drug: Prednisone; Drug: Prednisolone
Zilovertamab Vedotin + R-CHP: Efficacy ExpansionExperimentalParticipants 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).
Receives: Biological: Zilovertamab Vedotin; Drug: Cyclophosphamide; Drug: Doxorubicin; Biological: Rituximab; Biological: Rituximab Biosimilar; Drug: Prednisone; Drug: Prednisolone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) in Cycle 1

    DLTs will be evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 and are defined as any drug-related adverse event (AE) observed during the DLT evaluation period (e.g. Cycle 1) that results in a change to a given dose or a delay in initiating the next cycle. The number of participants with DLTs in Cycle 1 will be reported.

    Measured: Cycle 1 (up to 21 days)

  2. Number of Participants Who Experienced At Least One AE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experience an AE will be reported.

    Measured: Up to approximately 8 months

  3. Number of Participants Who Discontinued Study Treatment Due to an AE

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue study treatment due to an AE will be reported.

    Measured: Up to approximately 5.5 months

  4. Complete Response Rate (CRR) per Lugano Response Criteria

    CRR is defined as the percentage of participants who achieve a Complete Response (CR) per Lugano response criteria [Cheson, B. D., et al 2014] for malignant lymphoma as assessed by the investigator. Assessment includes anatomic imaging with computed tomography (CT) or magnetic resonance imaging (MRI), metabolic imaging with positron emission tomography (PET), and clinical findings including physical examination and bone marrow biopsy results. The percentage of participants with CRR will be reported.

    Measured: Up to approximately 60 months

Secondary outcomes (2)

  1. Objective Response Rate (ORR) per Lugano Response Criteria

    ORR is defined as the percentage of participants who achieve a CR or PR per Lugano response criteria [Cheson, B. D., et al 2014] for malignant lymphoma as assessed by the investigator. Assessment includes anatomic imaging with CT or MRI, metabolic imaging with PET, and clinical findings including physical examination and bone marrow biopsy results. The percentage of participants with ORR will be reported.

    Measured: Up to approximately 60 months

  2. Duration of Response (DOR) per Lugano Response Criteria

    For participants who demonstrate a confirmed CR or PR per Lugano response criteria [Cheson, B. D., et al 2014] for malignant lymphoma, DOR is defined as the time from the first documented evidence of CR or PR until disease progression or death due to any cause, whichever occurs first. CR and PR assessment includes anatomic imaging with CT or MRI, metabolic imaging with PET, and clinical findings including physical examination and bone marrow biopsy results. DOR as assessed by the investigator will be reported.

    Measured: Up to approximately 60 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Jun 2022
  2. Study start14 Jul 2022
  3. Primary completion26 Apr 2029 (estimated)
  4. Study completion26 Apr 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05406401
Sponsor's protocol ID
2140-007
Other IDs
MK-2140-007, 2022-501380-40, U1111-1280-2348, 2021-005861-41
Acronym
waveLINE-007
Status last verified
Oct 2024
First submitted
1 Jun 2022
Last updated
15 Oct 2024
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Zilovertamab Vedotin, Cyclophosphamide and Doxorubicin in people with Lymphoma, Large B-Cell, Diffuse (DLBCL), run by Merck Sharp & Dohme LLC at 22 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 15 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 22 sites in Italy, Poland, Canada, Spain, Turkey (Türkiye) and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Experienced Dose-limiting Toxicities (DLTs) in Cycle 1 (time frame: Cycle 1 (up to 21 days)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05406401.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2024.

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