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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04728893




Registration number
NCT04728893
Ethics application status
Date submitted
25/01/2021
Date registered
28/01/2021

Titles & IDs
Public title
Efficacy and Safety of Nemtabrutinib (MK-1026) in Participants With Hematologic Malignancies (MK-1026-003)
Scientific title
A Phase 2 Study to Evaluate the Efficacy and Safety of MK-1026 in Participants With Hematologic Malignancies
Secondary ID [1] 0 0
MK-1026-003
Secondary ID [2] 0 0
1026-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hematologic Malignancies 0 0
Waldenstroms Macroglobulinaemia 0 0
Non-Hodgkins Lymphoma 0 0
Chronic Lymphocytic Leukaemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
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
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Nemtabrutinib

Experimental: Nemtabrutinib - Participants receive nemtabrutinib orally once daily (QD) until progressive disease (PD) or discontinuation.


Treatment: Drugs: Nemtabrutinib
Nemtabrutinib tablets administered PO QD.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part 1: Number of participants experiencing dose-limiting toxicities (DLTs)
Timepoint [1] 0 0
Up to ~56 days (Cycles 1-2, cycle = 28 days)
Primary outcome [2] 0 0
Part 1: Number of participants experiencing adverse events (AEs)
Timepoint [2] 0 0
Up to ~71 months
Primary outcome [3] 0 0
Part 1: Number of participants discontinuing study treatment due to AEs
Timepoint [3] 0 0
Up to ~42 months
Primary outcome [4] 0 0
Part 2: Objective Response Rate (ORR) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) criteria 2018 as assessed by independent central review (ICR)
Timepoint [4] 0 0
Up to ~61 months
Primary outcome [5] 0 0
Part 2: ORR per Lugano criteria 2014 as assessed by ICR
Timepoint [5] 0 0
Up to ~61 months
Primary outcome [6] 0 0
Part 2: ORR per International Workshop on Waldenström's Macroglobulinemia (IWWM) criteria 2014 as assessed by ICR
Timepoint [6] 0 0
Up to ~71 months
Secondary outcome [1] 0 0
Part 1: Area Under the Curve (AUC) of Nemtabrutinib
Timepoint [1] 0 0
At designated time points (up to ~57 days)
Secondary outcome [2] 0 0
Part 1: Minimum Concentration (Cmin) of Nemtabrutinib
Timepoint [2] 0 0
At designated time points (up to ~57 days)
Secondary outcome [3] 0 0
Part 1: Maximum Concentration (Cmax) of Nemtabrutinib
Timepoint [3] 0 0
At designated time points (up to ~57 days)
Secondary outcome [4] 0 0
Part 1: ORR per iwCLL criteria 2018 as assessed by ICR
Timepoint [4] 0 0
Up to ~71 months
Secondary outcome [5] 0 0
Part 1: Duration of Response (DOR) per iwCLL criteria 2018 as assessed by ICR
Timepoint [5] 0 0
Up to ~71 months
Secondary outcome [6] 0 0
Part 2: Number of participants experiencing AEs
Timepoint [6] 0 0
Up to ~61 months
Secondary outcome [7] 0 0
Part 2: Number of participants discontinuing study treatment due to AEs
Timepoint [7] 0 0
Up to ~42 months
Secondary outcome [8] 0 0
Part 2: AUC of Nemtabrutinib
Timepoint [8] 0 0
At designated time points (up to ~57 days)
Secondary outcome [9] 0 0
Part 2: Cmin of Nemtabrutinib
Timepoint [9] 0 0
At designated time points (up to ~57 days)
Secondary outcome [10] 0 0
Part 2: Cmax of Nemtabrutinib
Timepoint [10] 0 0
At designated time points (up to ~57 days)
Secondary outcome [11] 0 0
Part 2: DOR per iwCLL criteria 2018 as assessed by ICR
Timepoint [11] 0 0
Up to ~61 months
Secondary outcome [12] 0 0
Part 2: DOR per Lugano criteria 2014 as assessed by ICR
Timepoint [12] 0 0
Up to ~61 months
Secondary outcome [13] 0 0
Part 2: DOR per IWWM criteria 2014 as assessed by ICR
Timepoint [13] 0 0
Up to ~61 months

Eligibility
Key inclusion criteria
* Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 within 7 days prior to allocation
* Has a life expectancy of at least 3 months, based on the investigator assessment
* Has the ability to swallow and retain oral medication
* Participants who are Hepatitis B surface antigen (HBsAg)-positive are eligible if they have received Hepatitis B virus (HBV) antiviral therapy for at least 4 weeks 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
* Has adequate organ function
* Male participants agree to refrain from donating sperm and agree to either remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle OR agree to use contraception, during the intervention period and for at least the time required to eliminate the study intervention after last dose of study intervention
* Female participants assigned female sex at birth who are not pregnant or breastfeeding are eligible to participate if not a participant of childbearing potential (POCBP), or if a POCBP they either use a contraceptive method that is highly effective OR remain abstinent from penile-vaginal intercourse as their preferred and usual lifestyle during the intervention period and for at least to eliminate study intervention after the last dose of study intervention
* Participants with HIV are eligible if they meet all of the following: the CD4 count is >350 cells/uL at screening, the HIV viral load is below the detectable level, are on a stable ART regimen for at least 4 weeks prior to study entry, and are compliant with their ART

Part 1 and Part 2 (Cohorts A to C and J)

* Has a confirmed diagnosis of CLL/SLL with

* At least 2 lines of prior therapy (Part 1 only)
* Part 2 Cohort A: CLL/SLL participants who are relapsed or refractory to prior therapy with a covalent, irreversible Bruton's tyrosine kinase inhibitor (BTKi), and a B-cell lymphoma 2 inhibitor (BCL2i). CLL participants must have received and failed, been intolerant to, or determined by their treating physician to be a poor phosphoinositide 3-kinase inhibitor (PI3Ki) candidate or ineligible for a PI3Ki per local guidelines
* Part 2 Cohort B: CLL/SLL participants who are relapsed or refractory following at least 1 line of prior therapy and are BTKi treatment naive
* Part 2 Cohort C: CLL/SLL participants with 17p deletion or tumor protein p53 (TP53) mutation who are relapsed or refractory following at least 1 line of prior therapy
* Part 2 Cohort J: CLL/SLL participants whose disease relapsed or was refractory to prior therapy with a covalent/irreversible BTKi and BCL2i
* Has active disease for CLL/SLL clearly documented to initiate therapy
* Has evaluable core or excisional lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate at Screening (optional for participants enrolling in Part 1)

Part 2 (Cohorts D to G)

* Has a confirmed diagnosis of and meets the following prior therapy requirements:

* Participants with Richter's transformation who are relapsed or refractory following at least 1 line of prior therapy (Cohort D)
* Participants with pathologically confirmed MCL, documented by either overexpression of cyclin D1 or t(11;14), who are relapsed or are refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort E)
* Participants with MZL (including splenic, nodal, and extra nodal MZL) who are relapsed or refractory to chemoimmunotherapy and a covalent irreversible BTKi (Cohort F)
* Participants with FL who are relapsed or refractory to chemoimmunotherapy, immunomodulatory agents (i.e. lenalidomide plus rituximab) (Cohort G)
* Have measurable disease defined as at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan
* Has a lymph node biopsy for biomarker analysis from an archival or newly obtained biopsy or bone marrow aspirate (Cohort D) at Screening

Part 2 (Cohort H): confirmed diagnosis of WM; participants who are relapsed or refractory to standard therapies for WM including chemoimmunotherapy and a covalent irreversible BTKi

* Has active disease defined as 1 of the following: systemic symptoms, physical findings, laboratory abnormalities, coexisting disease
* Has measurable disease, satisfying any of the following: at least 1 lesion that can be accurately measured in at least 2 dimensions with spiral CT scan (minimum measurement must be >15 mm in the longest diameter or >10 mm in the short axis); IgM =450 mg/dL; or bone marrow infiltration of 10%
* Has fresh bone marrow aspirate or a lymph node biopsy for biomarker analysis at Screening or a lymph node biopsy from an archival
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Has active HBV/HCV infection (Part 1 and Part 2)
* Has a history of malignancy =3 years before providing documented informed consent. Participants with basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potential curative therapy are not excluded. Participants with low-risk, early-stage prostate cancer (T1-T2a, Gleason score =6, and prostate-specific antigen <10 ng/mL) either treated with definitive intent or untreated in active surveillance with SD are not excluded
* Has active central nervous system (CNS) disease
* Has an active infection requiring systemic therapy
* Has received prior systemic anti-cancer therapy within 4 weeks prior to allocation
* Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
* Has any clinically significant gastrointestinal abnormalities that might alter absorption
* History of severe bleeding disorders

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Single group
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Nepean Hospital-Nepean Cancer Care Centre ( Site 0204) - Sydney
Recruitment hospital [2] 0 0
Box Hill Hospital ( Site 0203) - Box Hill
Recruitment hospital [3] 0 0
Sir Charles Gairdner Hospital ( Site 0200) - Nedlands
Recruitment postcode(s) [1] 0 0
2747 - Sydney
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Kentucky
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New Jersey
Country [7] 0 0
United States of America
State/province [7] 0 0
North Dakota
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
United States of America
State/province [9] 0 0
Washington
Country [10] 0 0
Argentina
State/province [10] 0 0
Buenos Aires
Country [11] 0 0
Argentina
State/province [11] 0 0
Caba
Country [12] 0 0
Argentina
State/province [12] 0 0
Santa Fe
Country [13] 0 0
Argentina
State/province [13] 0 0
Cordoba
Country [14] 0 0
Argentina
State/province [14] 0 0
Mendoza
Country [15] 0 0
Brazil
State/province [15] 0 0
Sao Paulo
Country [16] 0 0
Brazil
State/province [16] 0 0
Rio de Janeiro
Country [17] 0 0
Canada
State/province [17] 0 0
Alberta
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
China
State/province [20] 0 0
Anhui
Country [21] 0 0
China
State/province [21] 0 0
Beijing
Country [22] 0 0
China
State/province [22] 0 0
Chongqing
Country [23] 0 0
China
State/province [23] 0 0
Guangdong
Country [24] 0 0
China
State/province [24] 0 0
Guangxi
Country [25] 0 0
China
State/province [25] 0 0
Henan
Country [26] 0 0
China
State/province [26] 0 0
Hubei
Country [27] 0 0
China
State/province [27] 0 0
Hunan
Country [28] 0 0
China
State/province [28] 0 0
Jiangsu
Country [29] 0 0
China
State/province [29] 0 0
Jiangxi
Country [30] 0 0
China
State/province [30] 0 0
Jilin
Country [31] 0 0
China
State/province [31] 0 0
Shanghai
Country [32] 0 0
China
State/province [32] 0 0
Sichuan
Country [33] 0 0
China
State/province [33] 0 0
Tianjin
Country [34] 0 0
China
State/province [34] 0 0
Zhejiang
Country [35] 0 0
Czechia
State/province [35] 0 0
Brno-mesto
Country [36] 0 0
Czechia
State/province [36] 0 0
Hradec Kralove
Country [37] 0 0
Denmark
State/province [37] 0 0
Midtjylland
Country [38] 0 0
Denmark
State/province [38] 0 0
Nordjylland
Country [39] 0 0
Denmark
State/province [39] 0 0
Sjaelland
Country [40] 0 0
Denmark
State/province [40] 0 0
Syddanmark
Country [41] 0 0
France
State/province [41] 0 0
Alpes-Maritimes
Country [42] 0 0
France
State/province [42] 0 0
Bouches-du-Rhone
Country [43] 0 0
France
State/province [43] 0 0
Rhone-Alpes
Country [44] 0 0
France
State/province [44] 0 0
Yvelines
Country [45] 0 0
France
State/province [45] 0 0
Paris
Country [46] 0 0
Germany
State/province [46] 0 0
Baden-Wurttemberg
Country [47] 0 0
Germany
State/province [47] 0 0
Nordrhein-Westfalen
Country [48] 0 0
Germany
State/province [48] 0 0
Sachsen
Country [49] 0 0
Hungary
State/province [49] 0 0
Baranya
Country [50] 0 0
Hungary
State/province [50] 0 0
Hajdu-Bihar
Country [51] 0 0
Hungary
State/province [51] 0 0
Szabolcs-Szatmar-Bereg
Country [52] 0 0
Hungary
State/province [52] 0 0
Budapest
Country [53] 0 0
Ireland
State/province [53] 0 0
Dublin
Country [54] 0 0
Ireland
State/province [54] 0 0
Limerick
Country [55] 0 0
Israel
State/province [55] 0 0
Afula
Country [56] 0 0
Israel
State/province [56] 0 0
Beer-Sheva
Country [57] 0 0
Israel
State/province [57] 0 0
Haifa
Country [58] 0 0
Israel
State/province [58] 0 0
Jerusalem
Country [59] 0 0
Israel
State/province [59] 0 0
Ramat Gan
Country [60] 0 0
Israel
State/province [60] 0 0
Rehovot
Country [61] 0 0
Israel
State/province [61] 0 0
Tel Aviv
Country [62] 0 0
Italy
State/province [62] 0 0
Bari
Country [63] 0 0
Italy
State/province [63] 0 0
Bologna
Country [64] 0 0
Italy
State/province [64] 0 0
Brescia
Country [65] 0 0
Italy
State/province [65] 0 0
Milano
Country [66] 0 0
Italy
State/province [66] 0 0
Napoli
Country [67] 0 0
Italy
State/province [67] 0 0
Pavia
Country [68] 0 0
Italy
State/province [68] 0 0
Reggio Emilia
Country [69] 0 0
Italy
State/province [69] 0 0
Roma
Country [70] 0 0
Korea, Republic of
State/province [70] 0 0
Seoul
Country [71] 0 0
Poland
State/province [71] 0 0
Dolnoslaskie
Country [72] 0 0
Poland
State/province [72] 0 0
Malopolskie
Country [73] 0 0
Poland
State/province [73] 0 0
Mazowieckie
Country [74] 0 0
Poland
State/province [74] 0 0
Opolskie
Country [75] 0 0
Poland
State/province [75] 0 0
Pomorskie
Country [76] 0 0
Romania
State/province [76] 0 0
Bucuresti
Country [77] 0 0
Romania
State/province [77] 0 0
Constanta
Country [78] 0 0
Romania
State/province [78] 0 0
Brasov
Country [79] 0 0
Romania
State/province [79] 0 0
Iasi
Country [80] 0 0
Spain
State/province [80] 0 0
Barcelona
Country [81] 0 0
Spain
State/province [81] 0 0
La Coruna
Country [82] 0 0
Spain
State/province [82] 0 0
Alicante
Country [83] 0 0
Spain
State/province [83] 0 0
Madrid
Country [84] 0 0
Spain
State/province [84] 0 0
Salamanca
Country [85] 0 0
Switzerland
State/province [85] 0 0
Berne
Country [86] 0 0
Switzerland
State/province [86] 0 0
Ticino
Country [87] 0 0
Turkey
State/province [87] 0 0
Istanbul
Country [88] 0 0
Turkey
State/province [88] 0 0
Ankara
Country [89] 0 0
Turkey
State/province [89] 0 0
Izmir
Country [90] 0 0
Ukraine
State/province [90] 0 0
Cherkaska Oblast
Country [91] 0 0
Ukraine
State/province [91] 0 0
Ivano-Frankivska Oblast
Country [92] 0 0
Ukraine
State/province [92] 0 0
Lvivska Oblast
Country [93] 0 0
Ukraine
State/province [93] 0 0
Kyiv
Country [94] 0 0
United Kingdom
State/province [94] 0 0
Bristol, City Of
Country [95] 0 0
United Kingdom
State/province [95] 0 0
England
Country [96] 0 0
United Kingdom
State/province [96] 0 0
London, City Of
Country [97] 0 0
United Kingdom
State/province [97] 0 0
Oxfordshire
Country [98] 0 0
United Kingdom
State/province [98] 0 0
Suffolk
Country [99] 0 0
United Kingdom
State/province [99] 0 0
Surrey
Country [100] 0 0
United Kingdom
State/province [100] 0 0
Manchester

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
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.