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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/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
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Oxford
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Plymouth
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Windsor
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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
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/ct2/show/NCT04662255
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



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04662255