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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05139017




Registration number
NCT05139017
Ethics application status
Date submitted
11/11/2021
Date registered
1/12/2021

Titles & IDs
Public title
A Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (rrDLBCL) (MK-2140-003)
Scientific title
A Phase 2/3 Multicenter, Open-label, Randomized, Active-Control Study of Zilovertamab Vedotin (MK-2140) in Combination With Standard of Care in Participants With Relapsed or Refractory Diffuse Large B-Cell Lymphoma (waveLINE-003)
Secondary ID [1] 0 0
VLS-101
Secondary ID [2] 0 0
2140-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
DLBCL 0 0
Diffuse Large B-Cell Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - Zilovertamab vedotin
Treatment: Other - Rituximab
Treatment: Drugs - Gemcitabine
Treatment: Drugs - Oxaliplatin
Treatment: Drugs - Bendamustine

Experimental: ZV + R-GemOx (Part 1) - Participants in this arm will receive doses of ZV (from 1.5 mg/Kg up to 2.5 mg/Kg) plus Rituximab 375 mg/m\^2, Gemcitabine 1000 mg/m\^2 and Oxaliplatin 100 mg/m\^2 (R-GemOx) given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles.

Experimental: ZV + R-GemOx (Part 2) - Using the recommended Phase 2 dose (RP2D) dose of ZV plus R-GemOx from Part 1, participants will receive ZV plus R-GemOx given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.

Active comparator: R-GemOx (active control for Part 2) - Participants will receive R-GemOx given intravenously on Day 1 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.

Experimental: ZV + BR (Part 2) - Using RP2D from Part 1, participants will receive ZV plus Rituximab 375 mg/m\^2, given intravenously on Day 1 and Bendamustine 90 mg/m\^2 given intravenously on Day 1 and 2, of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.

Active comparator: Bendamustine Rituximab (BR) - Participants will receive Rituximab 375 mg/m\^2, given intravenously on Day 1 Bendamustine 90 mg/m\^2 given intravenously on Day 1 and 2 of repeated 21-day cycles. Treatment will continue for up to 6 cycles or until progressive disease or discontinuation.

Experimental: ZV + BR (Part 1) - Participants in this arm will receive doses of ZV (from 1.5 mg/Kg up to 2.5 mg/Kg) plus Rituximab 375 mg/m\^2, Bendamustine 90 mg/m\^2 (BR) given intravenously on Day 1 and 2 of repeated 21-day cycles. Treatment will continue for up to 6 cycles.


Treatment: Other: Zilovertamab vedotin
Intravenous (IV) Infusion 1.5 mg/kg, 1.75 mg/kg, 2.0 mg/kg, 2.25 mg/kg, 2.5 mg/kg

Treatment: Other: Rituximab
IV Infusion 375 mg/m\^2

Treatment: Drugs: Gemcitabine
IV Infusion 1000 mg/m\^2

Treatment: Drugs: Oxaliplatin
IV Infusion 100 mg/m\^2

Treatment: Drugs: Bendamustine
IV Infusion 90 mg/m\^2
Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of participants who experienced dose-limiting toxicities (DLTs) in Part 1
Timepoint [1] 0 0
Up to ~6 weeks
Primary outcome [2] 0 0
Number of participants who experienced an adverse event (AE)
Timepoint [2] 0 0
Up to ~35 months
Primary outcome [3] 0 0
Number of participants who discontinued study treatment due to an AE
Timepoint [3] 0 0
Up to ~35 months
Primary outcome [4] 0 0
Overall survival (OS)
Timepoint [4] 0 0
Up to ~35 months
Primary outcome [5] 0 0
Progression-free survival (PFS)
Timepoint [5] 0 0
Up to ~26 months
Secondary outcome [1] 0 0
Objective response rate (ORR)
Timepoint [1] 0 0
Up to ~26 months
Secondary outcome [2] 0 0
Duration of response (DOR)
Timepoint [2] 0 0
Up to ~26 months

Eligibility
Key inclusion criteria
* Has a histologically confirmed diagnosis of Diffuse Large B-Cell Lymphoma (DLBCL).
* Has radiographically measurable DLBCL per the Lugano Response Criteria, as assessed locally by the investigator.
* Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 within 7 days prior to study treatment initiation.
* Has adequate organ function.
* Is able to provide new or archival tumor tissue sample not previously irradiated.

Zilovertamab vedotin plus R-GemOx, or R-GemOx study arms:

* Has relapsed or refractory DLBCL and is ineligible for or have failed autologous stem-cell transplant (ASCT) and have failed at least 1 line of prior therapy.
* Has post-chimeric antigen receptor T (post-CAR-T) cell therapy failure or is ineligible for CAR-T cell therapy.

Not applicable with protocol amendment 4: Zilovertamab vedotin plus Bendamustine Rituximab (BR), and Bendamustine Rituximab study arms:

* Has relapsed or refractory DLBCL and is ineligible for or have failed ASCT and have failed at least 2 lines of prior therapy.
* Has post-CAR-T therapy failure or is ineligible for CAR-T cell therapy.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Not applicable with protocol amendment 4: Has 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 or serious cardiac arrhythmia requiring medication.
* Has ongoing graft-versus-host disease (GVHD) of any grade, or is receiving treatment for their GVHD.
* Has pericardial effusion or clinically significant pleural effusion.
* Has ongoing Grade >1 peripheral neuropathy.
* Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years.
* Has a demyelinating form of Charcot-Marie-Tooth disease.
* Has contraindication to any of the study intervention components including but not limited to prior anaphylactic reaction.
* Has received prior systemic anticancer therapy, including investigational agents within 4 weeks prior to the first dose of study intervention.
* Has received prior radiotherapy within 4 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
* Has ongoing corticosteroid therapy.
* Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
* Has known active central nervous system (CNS) lymphoma involvement or active CNS involvement by lymphoma. Participants with prior CNS involvement are eligible if their CNS disease is in radiographic, cytological (for cerebrospinal fluid disease), and clinical remission.
* 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 psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/01/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
24/09/2027
Actual
Sample size
Target
290
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Grampians Health ( Site 1802) - Ballarat
Recruitment postcode(s) [1] 0 0
3350 - Ballarat
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Kentucky
Country [3] 0 0
United States of America
State/province [3] 0 0
Louisiana
Country [4] 0 0
United States of America
State/province [4] 0 0
Maryland
Country [5] 0 0
United States of America
State/province [5] 0 0
Massachusetts
Country [6] 0 0
United States of America
State/province [6] 0 0
Montana
Country [7] 0 0
United States of America
State/province [7] 0 0
New Jersey
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
Tennessee
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
China
State/province [11] 0 0
Beijing
Country [12] 0 0
China
State/province [12] 0 0
Chongqing
Country [13] 0 0
China
State/province [13] 0 0
Guangdong
Country [14] 0 0
China
State/province [14] 0 0
Henan
Country [15] 0 0
China
State/province [15] 0 0
Hubei
Country [16] 0 0
China
State/province [16] 0 0
Jiangxi
Country [17] 0 0
China
State/province [17] 0 0
Jilin
Country [18] 0 0
China
State/province [18] 0 0
Shanghai
Country [19] 0 0
China
State/province [19] 0 0
Sichuan
Country [20] 0 0
Costa Rica
State/province [20] 0 0
San Jose
Country [21] 0 0
France
State/province [21] 0 0
Rhone
Country [22] 0 0
France
State/province [22] 0 0
Paris
Country [23] 0 0
Guatemala
State/province [23] 0 0
Guatemala
Country [24] 0 0
Hong Kong
State/province [24] 0 0
Hong Kong
Country [25] 0 0
Israel
State/province [25] 0 0
Afula
Country [26] 0 0
Israel
State/province [26] 0 0
Haifa
Country [27] 0 0
Israel
State/province [27] 0 0
Jerusalem
Country [28] 0 0
Italy
State/province [28] 0 0
Lazio
Country [29] 0 0
Italy
State/province [29] 0 0
Milano
Country [30] 0 0
Italy
State/province [30] 0 0
Bologna
Country [31] 0 0
Italy
State/province [31] 0 0
Napoli
Country [32] 0 0
Korea, Republic of
State/province [32] 0 0
Seoul
Country [33] 0 0
Poland
State/province [33] 0 0
Dolnoslaskie
Country [34] 0 0
Poland
State/province [34] 0 0
Lubelskie
Country [35] 0 0
Poland
State/province [35] 0 0
Malopolskie
Country [36] 0 0
Poland
State/province [36] 0 0
Mazowieckie
Country [37] 0 0
Poland
State/province [37] 0 0
Pomorskie
Country [38] 0 0
Thailand
State/province [38] 0 0
Krung Thep Maha Nakhon
Country [39] 0 0
Thailand
State/province [39] 0 0
Chiang Mai
Country [40] 0 0
Turkey
State/province [40] 0 0
Izmir
Country [41] 0 0
Turkey
State/province [41] 0 0
Ankara
Country [42] 0 0
Turkey
State/province [42] 0 0
Istanbul
Country [43] 0 0
Turkey
State/province [43] 0 0
Samsun
Country [44] 0 0
Ukraine
State/province [44] 0 0
Cherkaska Oblast
Country [45] 0 0
Ukraine
State/province [45] 0 0
Lvivska Oblast
Country [46] 0 0
Ukraine
State/province [46] 0 0
Kyiv
Country [47] 0 0
United Kingdom
State/province [47] 0 0
London, City Of

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Toll Free Number
Address 0 0
Country 0 0
Phone 0 0
1-888-577-8839
Fax 0 0
Email 0 0
Trialsites@msd.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: http://engagezone.msd.com/ds_documentation.php


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05139017