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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

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
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Alaska
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Nebraska
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Oregon
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Aquitaine
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Tours Cedex 9
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Paris
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Pessac Cedex
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Pierre Benite Cedex
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Politiers
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Baden-Württemberg
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Bayern
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Rhineland-Palatinate
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Schleswig Holstein
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Hamburg
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Mainz
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Munster
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Baranya
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Debrecen
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Dublin 8
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Haifa
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Ramat Gan
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AL
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Ancona
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Bari
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Emilia-Romagna
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Italy
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Lombardia
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Italy
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Potenza
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Bologna
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Genova
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Messina
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Pisa
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Ravenna
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Italy
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Reggio Emilia
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Varese
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Japan
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Aichi
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Hyogo
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Miyagi
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Osaka
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Saitama
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Tokyo
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Hiroshima
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Kumamoto
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Kyoto-shi
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Japan
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Okayama
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Korea, Republic of
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Incheon-gwangyeoksi [Incheon]
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Korea, Republic of
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Seogu
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Korea, Republic of
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Seoul, Korea
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Korea, Republic of
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Seoul-teukbyeolsi [Seoul]
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Korea, Republic of
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Seoul
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Korea, Republic of
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Busan
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Netherlands
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Den Haag
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Roosendaal
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Rotterdam
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TM Hoofddorp
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New Zealand
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Auckland
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Christchurch
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Poland
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Lubelskie
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Krakow
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Wroclaw
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Lódz
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Portugal
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Lisboa
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Russian Federation
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Omskaya Oblast'
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Russian Federation
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Moscow
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Russian Federation
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Saint Petersburg
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Russian Federation
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Saint-Petersburg
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Spain
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Andalucia
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Spain
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Barcelona
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Spain
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A Coruña
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Spain
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Madrid
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Spain
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Pamplona
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Spain
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Sevilla
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Spain
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Valencia
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Switzerland
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Luzern
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Switzerland
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Bellinzona
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Taiwan
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Taipei
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Taiwan
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Chiayi County
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Kaohsiung
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Taiwan
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Taichung
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Taiwan
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Tainan
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Taiwan
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Taoyuan City
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United Kingdom
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Aberdeen City
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United Kingdom
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Oxford
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United Kingdom
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Stratchclyde
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United Kingdom
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Surrey
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United Kingdom
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Newmarket
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United Kingdom
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Nottingham
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United Kingdom
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Plymouth
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United Kingdom
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Windsor
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United Kingdom
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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
Trial website
Trial related presentations / publications
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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/NCT04662255