Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04662255




Registration number
NCT04662255
Ethics application status
Date submitted
4/12/2020
Date registered
10/12/2020
Date last updated
13/05/2024

Titles & IDs
Public title
Study of BTK Inhibitor LOXO-305 Versus Approved BTK Inhibitor Drugs in Patients With Mantle Cell Lymphoma (MCL)
Scientific title
A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator Choice of BTK Inhibitor in Patients With Previously Treated BTK Inhibitor Naïve Mantle Cell Lymphoma (BRUIN MCL-321)
Secondary ID [1] 0 0
J2N-OX-JZNM
Secondary ID [2] 0 0
LOXO-BTK-20019
Universal Trial Number (UTN)
Trial acronym
BRUIN-MCL-321
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lymphoma, Mantle-Cell 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(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - Pirtobrutinib
Treatment: Drugs - Ibrutinib
Treatment: Drugs - Acalabrutinib
Treatment: Drugs - Zanubrutinib

Experimental: Arm A (Pirtobrutinib) - Orally

Active comparator: Arm B (Ibrutinib, Acalabrutinib, or Zanubrutinib) - Investigator's choice (based on local availability) of ibrutinib, acalabrutinib or zanubrutinib orally. Options are limited to those that are available/approved in the specific country.


Treatment: Drugs: Pirtobrutinib
Oral

Treatment: Drugs: Ibrutinib
Oral

Treatment: Drugs: Acalabrutinib
Oral

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

Outcomes
Primary outcome [1] 0 0
To compare progression-free survival (PFS) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) in patients with previously treated mantle cell lymphoma (MCL)
Timepoint [1] 0 0
Up to approximately 24 months
Secondary outcome [1] 0 0
To compare Event Free Survival (EFS) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms
Timepoint [1] 0 0
Up to approximately 24 months
Secondary outcome [2] 0 0
To compare Time to Treatment Failure (TTTF) as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms
Timepoint [2] 0 0
Up to approximately 24 months
Secondary outcome [3] 0 0
Time to worsening (TTW) of MCL-related symptoms
Timepoint [3] 0 0
Up to approximately 24 months
Secondary outcome [4] 0 0
Comparative Tolerability as measured by proportion of time with high side effect burden
Timepoint [4] 0 0
Up to approximately 24 months
Secondary outcome [5] 0 0
To compare Overall Response Rate (ORR) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms
Timepoint [5] 0 0
Up to approximately 24 months
Secondary outcome [6] 0 0
To compare Duration of Response (DOR) of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms
Timepoint [6] 0 0
Up to approximately 24 months
Secondary outcome [7] 0 0
To compare Overall Survival of pirtobrutinib as monotherapy (Arm A) to investigator choice of covalent BTK inhibitor monotherapy (Arm B) treatment arms
Timepoint [7] 0 0
Up to approximately 24 months

Eligibility
Key inclusion criteria
* Confirmed MCL diagnosis
* Previously treated with at least one prior line of systemic therapy for MCL
* Measurable disease per Lugano criteria
* Eastern Cooperative Oncology Group (ECOG) 0-2
* Absolute neutrophil count = 0.75 × 109/L without granulocyte-colony stimulating factor support within 7 days of screening
* Hemoglobin = 8 g/dL not requiring transfusion support or growth factors within 7 days of screening
* Platelets = 50 × 109/L not requiring transfusion support or growth factors within 7 days of screening.
* AST and ALT = 3.0 x upper limit of normal (ULN)
* Total bilirubin = 1.5 x ULN.
* Creatinine clearance of = 30 mL/min according to Cockcroft/Gault Formula
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with an approved or investigational BTK inhibitor
* History of bleeding diathesis
* History of stroke or intracranial hemorrhage within 6 months of randomization
* History of allogeneic or autologous stem cell transplant (SCT) or chimeric antigen receptor modified T-cell (CAR-T) therapy within 60 days of randomization
* Clinically significant cardiovascular disease
* Prolonged QT interval corrected using Fridericia's formula (QTcF) > 470 ms on 2/3 consecutive ECGs, and mean QTcF>470 ms on all 3 ECGs
* Known HIV infection or active HBV, HCV, or CMV infections. (Certain participants with controlled HBV infections may still be eligible)
* Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal (GI) absorption
* Ongoing chronic treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment.
* Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist.
* Vaccination with live vaccine within 28 days prior to randomization

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
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/04/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2026
Actual
Sample size
Target
500
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
The St. George Hospital - Kogarah
Recruitment hospital [2] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [3] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [4] 0 0
Andrew Lowe Cancer Centre - Geelong
Recruitment hospital [5] 0 0
Linear Clinical Research Ltd - Nedlands
Recruitment hospital [6] 0 0
Royal Perth Hospital - Perth
Recruitment hospital [7] 0 0
Icon Cancer Care - The Wesley Medical Centre - Auchenflower
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
5042 - Adelaide
Recruitment postcode(s) [3] 0 0
7000 - Hobart
Recruitment postcode(s) [4] 0 0
3220 - Geelong
Recruitment postcode(s) [5] 0 0
WA6009 - Nedlands
Recruitment postcode(s) [6] 0 0
6000 - Perth
Recruitment postcode(s) [7] 0 0
4066 - Auchenflower
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alaska
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Delaware
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Kentucky
Country [8] 0 0
United States of America
State/province [8] 0 0
Louisiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Maryland
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Minnesota
Country [13] 0 0
United States of America
State/province [13] 0 0
Missouri
Country [14] 0 0
United States of America
State/province [14] 0 0
Nebraska
Country [15] 0 0
United States of America
State/province [15] 0 0
Nevada
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New York
Country [18] 0 0
United States of America
State/province [18] 0 0
North Carolina
Country [19] 0 0
United States of America
State/province [19] 0 0
Ohio
Country [20] 0 0
United States of America
State/province [20] 0 0
Oregon
Country [21] 0 0
United States of America
State/province [21] 0 0
Pennsylvania
Country [22] 0 0
United States of America
State/province [22] 0 0
Tennessee
Country [23] 0 0
United States of America
State/province [23] 0 0
Texas
Country [24] 0 0
United States of America
State/province [24] 0 0
Utah
Country [25] 0 0
United States of America
State/province [25] 0 0
Virginia
Country [26] 0 0
United States of America
State/province [26] 0 0
Washington
Country [27] 0 0
United States of America
State/province [27] 0 0
Wisconsin
Country [28] 0 0
Austria
State/province [28] 0 0
Oberösterreich
Country [29] 0 0
Austria
State/province [29] 0 0
Osterreich
Country [30] 0 0
Belgium
State/province [30] 0 0
Gent
Country [31] 0 0
Belgium
State/province [31] 0 0
Leuven
Country [32] 0 0
Belgium
State/province [32] 0 0
Roeselare
Country [33] 0 0
Brazil
State/province [33] 0 0
Ceará
Country [34] 0 0
Brazil
State/province [34] 0 0
Goiás
Country [35] 0 0
Brazil
State/province [35] 0 0
Maranhão
Country [36] 0 0
Brazil
State/province [36] 0 0
Paraná
Country [37] 0 0
Brazil
State/province [37] 0 0
Sao Paulo
Country [38] 0 0
Brazil
State/province [38] 0 0
São Paulo
Country [39] 0 0
Brazil
State/province [39] 0 0
Rio De Janeiro
Country [40] 0 0
Brazil
State/province [40] 0 0
Rio de Janeiro
Country [41] 0 0
Canada
State/province [41] 0 0
Alberta
Country [42] 0 0
Canada
State/province [42] 0 0
British Columbia
Country [43] 0 0
Canada
State/province [43] 0 0
Manitoba
Country [44] 0 0
Canada
State/province [44] 0 0
Ontario
Country [45] 0 0
China
State/province [45] 0 0
Anhui
Country [46] 0 0
China
State/province [46] 0 0
Beijing
Country [47] 0 0
China
State/province [47] 0 0
Fujian
Country [48] 0 0
China
State/province [48] 0 0
Guangdong
Country [49] 0 0
China
State/province [49] 0 0
Henan
Country [50] 0 0
China
State/province [50] 0 0
Hubei
Country [51] 0 0
China
State/province [51] 0 0
Hunan
Country [52] 0 0
China
State/province [52] 0 0
Jiangsu
Country [53] 0 0
China
State/province [53] 0 0
Jiangxi
Country [54] 0 0
China
State/province [54] 0 0
Jilin
Country [55] 0 0
China
State/province [55] 0 0
Liaoning
Country [56] 0 0
China
State/province [56] 0 0
Sichuan
Country [57] 0 0
China
State/province [57] 0 0
Tianjin
Country [58] 0 0
China
State/province [58] 0 0
Xinjiang
Country [59] 0 0
China
State/province [59] 0 0
Zhejiang
Country [60] 0 0
China
State/province [60] 0 0
Chongqing
Country [61] 0 0
China
State/province [61] 0 0
Shanghai
Country [62] 0 0
Czechia
State/province [62] 0 0
Brno
Country [63] 0 0
Czechia
State/province [63] 0 0
Hradec Kralove
Country [64] 0 0
Denmark
State/province [64] 0 0
Jutland
Country [65] 0 0
Denmark
State/province [65] 0 0
Odense
Country [66] 0 0
France
State/province [66] 0 0
Aquitaine
Country [67] 0 0
France
State/province [67] 0 0
Seine-Maritime
Country [68] 0 0
France
State/province [68] 0 0
Tours Cedex 9
Country [69] 0 0
France
State/province [69] 0 0
Lille cedex
Country [70] 0 0
France
State/province [70] 0 0
Nantes Cedex 1
Country [71] 0 0
France
State/province [71] 0 0
Paris
Country [72] 0 0
France
State/province [72] 0 0
Pessac Cedex
Country [73] 0 0
France
State/province [73] 0 0
Pierre Benite Cedex
Country [74] 0 0
France
State/province [74] 0 0
Politiers
Country [75] 0 0
France
State/province [75] 0 0
Vandœuvre-lès-Nancy
Country [76] 0 0
France
State/province [76] 0 0
Île-de-France
Country [77] 0 0
Germany
State/province [77] 0 0
Baden-Württemberg
Country [78] 0 0
Germany
State/province [78] 0 0
Bayern
Country [79] 0 0
Germany
State/province [79] 0 0
Nordrhein-Westfalen
Country [80] 0 0
Germany
State/province [80] 0 0
Rhineland-Palatinate
Country [81] 0 0
Germany
State/province [81] 0 0
Schleswig Holstein
Country [82] 0 0
Germany
State/province [82] 0 0
Hamburg
Country [83] 0 0
Germany
State/province [83] 0 0
Mainz
Country [84] 0 0
Germany
State/province [84] 0 0
Munster
Country [85] 0 0
Hungary
State/province [85] 0 0
Baranya
Country [86] 0 0
Hungary
State/province [86] 0 0
Debrecen
Country [87] 0 0
Ireland
State/province [87] 0 0
Dublin 8
Country [88] 0 0
Israel
State/province [88] 0 0
Haifa
Country [89] 0 0
Israel
State/province [89] 0 0
Jerusalem
Country [90] 0 0
Israel
State/province [90] 0 0
Ramat Gan
Country [91] 0 0
Israel
State/province [91] 0 0
Tel Aviv
Country [92] 0 0
Italy
State/province [92] 0 0
AL
Country [93] 0 0
Italy
State/province [93] 0 0
Ancona
Country [94] 0 0
Italy
State/province [94] 0 0
Bari
Country [95] 0 0
Italy
State/province [95] 0 0
Emilia-Romagna
Country [96] 0 0
Italy
State/province [96] 0 0
Lombardia
Country [97] 0 0
Italy
State/province [97] 0 0
Potenza
Country [98] 0 0
Italy
State/province [98] 0 0
Bologna
Country [99] 0 0
Italy
State/province [99] 0 0
Genova
Country [100] 0 0
Italy
State/province [100] 0 0
Messina
Country [101] 0 0
Italy
State/province [101] 0 0
Palermo
Country [102] 0 0
Italy
State/province [102] 0 0
Pisa
Country [103] 0 0
Italy
State/province [103] 0 0
Ravenna
Country [104] 0 0
Italy
State/province [104] 0 0
Reggio Emilia
Country [105] 0 0
Italy
State/province [105] 0 0
Varese
Country [106] 0 0
Japan
State/province [106] 0 0
Aichi
Country [107] 0 0
Japan
State/province [107] 0 0
Hokkaido
Country [108] 0 0
Japan
State/province [108] 0 0
Hyogo
Country [109] 0 0
Japan
State/province [109] 0 0
Kochi
Country [110] 0 0
Japan
State/province [110] 0 0
Miyagi
Country [111] 0 0
Japan
State/province [111] 0 0
Osaka
Country [112] 0 0
Japan
State/province [112] 0 0
Saitama
Country [113] 0 0
Japan
State/province [113] 0 0
Tokyo
Country [114] 0 0
Japan
State/province [114] 0 0
Hiroshima
Country [115] 0 0
Japan
State/province [115] 0 0
Kumamoto
Country [116] 0 0
Japan
State/province [116] 0 0
Kyoto-shi
Country [117] 0 0
Japan
State/province [117] 0 0
Okayama
Country [118] 0 0
Korea, Republic of
State/province [118] 0 0
Incheon-gwangyeoksi [Incheon]
Country [119] 0 0
Korea, Republic of
State/province [119] 0 0
Seogu
Country [120] 0 0
Korea, Republic of
State/province [120] 0 0
Seoul, Korea
Country [121] 0 0
Korea, Republic of
State/province [121] 0 0
Seoul-teukbyeolsi [Seoul]
Country [122] 0 0
Korea, Republic of
State/province [122] 0 0
Seoul
Country [123] 0 0
Korea, Republic of
State/province [123] 0 0
Busan
Country [124] 0 0
Netherlands
State/province [124] 0 0
Den Haag
Country [125] 0 0
Netherlands
State/province [125] 0 0
Roosendaal
Country [126] 0 0
Netherlands
State/province [126] 0 0
Rotterdam
Country [127] 0 0
Netherlands
State/province [127] 0 0
TM Hoofddorp
Country [128] 0 0
New Zealand
State/province [128] 0 0
Auckland
Country [129] 0 0
New Zealand
State/province [129] 0 0
Christchurch
Country [130] 0 0
Poland
State/province [130] 0 0
Lubelskie
Country [131] 0 0
Poland
State/province [131] 0 0
Pomorskie
Country [132] 0 0
Poland
State/province [132] 0 0
Krakow
Country [133] 0 0
Poland
State/province [133] 0 0
Skórzewo
Country [134] 0 0
Poland
State/province [134] 0 0
Wroclaw
Country [135] 0 0
Poland
State/province [135] 0 0
Lódz
Country [136] 0 0
Portugal
State/province [136] 0 0
Lisboa
Country [137] 0 0
Russian Federation
State/province [137] 0 0
Omskaya Oblast'
Country [138] 0 0
Russian Federation
State/province [138] 0 0
Moscow
Country [139] 0 0
Russian Federation
State/province [139] 0 0
Saint Petersburg
Country [140] 0 0
Russian Federation
State/province [140] 0 0
Saint-Petersburg
Country [141] 0 0
Spain
State/province [141] 0 0
Andalucia
Country [142] 0 0
Spain
State/province [142] 0 0
Barcelona
Country [143] 0 0
Spain
State/province [143] 0 0
A Coruña
Country [144] 0 0
Spain
State/province [144] 0 0
Madrid
Country [145] 0 0
Spain
State/province [145] 0 0
Pamplona
Country [146] 0 0
Spain
State/province [146] 0 0
Sevilla
Country [147] 0 0
Spain
State/province [147] 0 0
Valencia
Country [148] 0 0
Switzerland
State/province [148] 0 0
Luzern
Country [149] 0 0
Switzerland
State/province [149] 0 0
Bellinzona
Country [150] 0 0
Taiwan
State/province [150] 0 0
Taipei
Country [151] 0 0
Taiwan
State/province [151] 0 0
Chiayi County
Country [152] 0 0
Taiwan
State/province [152] 0 0
Kaohsiung
Country [153] 0 0
Taiwan
State/province [153] 0 0
Taichung
Country [154] 0 0
Taiwan
State/province [154] 0 0
Tainan
Country [155] 0 0
Taiwan
State/province [155] 0 0
Taoyuan City
Country [156] 0 0
United Kingdom
State/province [156] 0 0
Aberdeen City
Country [157] 0 0
United Kingdom
State/province [157] 0 0
Oxford
Country [158] 0 0
United Kingdom
State/province [158] 0 0
Stratchclyde
Country [159] 0 0
United Kingdom
State/province [159] 0 0
Surrey
Country [160] 0 0
United Kingdom
State/province [160] 0 0
Newmarket
Country [161] 0 0
United Kingdom
State/province [161] 0 0
Nottingham
Country [162] 0 0
United Kingdom
State/province [162] 0 0
Plymouth
Country [163] 0 0
United Kingdom
State/province [163] 0 0
Windsor
Country [164] 0 0
United Kingdom
State/province [164] 0 0
Wolverhampton

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Loxo Oncology, Inc.
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Eli Lilly and Company
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
This is a study for participants with a type of blood cancer called mantle cell lymphoma (MCL). The main purpose is to compare pirtobrutinib (LOXO-305) to other drugs that work in a similar way that have already been approved by the United States Food and Drug Administration (US FDA). Participation could last up to two years, and possibly longer, if the disease does not progress.
Trial website
https://clinicaltrials.gov/study/NCT04662255
Trial related presentations / publications
Eyre TA, Shah NN, Dreyling M, Jurczak W, Wang Y, Cheah CY, Song Y, Gandhi M, Chay C, Sharman J, Andorsky DJ, Messersmith HM, Ruppert AS, Muthig VA, Ito R, Wang ML. BRUIN MCL-321: phase III study of pirtobrutinib versus investigator choice of BTK inhibitor in BTK inhibitor naive mantle cell lymphoma. Future Oncol. 2022 Nov;18(36):3961-3969. doi: 10.2217/fon-2022-0976. Epub 2022 Nov 15.
Ito R, Eyre TA, Shah NN, Gouill SL, Dreyling M, Vandenberghe E, Jurczak W, Wang Y, Cheah CY, Gandhi M, Chay C, Sharman J, Andorsky DJ, Song Y, Stark A, Muthig V, Wang ML. MCL-135 BRUIN MCL-321, a Phase 3 Open-Label, Randomized Study of Pirtobrutinib Versus Investigator Choice of BTK Inhibitor in Patients With Previously Treated, BTK Inhibitor Naive Mantle Cell Lymphoma (Trial in Progress). Clin Lymphoma Myeloma Leuk. 2022 Oct;22 Suppl 2:S395-S396. doi: 10.1016/S2152-2650(22)01570-1.
Public notes

Contacts
Principal investigator
Name 0 0
Patient Advocacy
Address 0 0
Loxo Oncology, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT04662255