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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/NCT04965493




Registration number
NCT04965493
Ethics application status
Date submitted
15/07/2021
Date registered
16/07/2021
Date last updated
13/05/2024

Titles & IDs
Public title
A Trial of Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab (PVR) Versus Venetoclax and Rituximab (VR) in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)
Scientific title
A Phase 3 Open-Label, Randomized Study of Fixed Duration Pirtobrutinib (LOXO-305) Plus Venetoclax and Rituximab Versus Venetoclax and Rituximab in Previously Treated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-322)
Secondary ID [1] 0 0
J2N-OX-JZNO
Secondary ID [2] 0 0
LOXO-BTK-20022
Universal Trial Number (UTN)
Trial acronym
BRUIN CLL-322
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia 0 0
Small Lymphocytic 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
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

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

Experimental: Arm A (PVR) - Fixed duration pirtobrutinib in combination with venetoclax and rituximab

Active Comparator: Arm B (VR) - Venetoclax with rituximab


Treatment: Drugs: Pirtobrutinib
Oral

Treatment: Drugs: Venetoclax
Oral

Treatment: Drugs: Rituximab
Intravenous (IV)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To evaluate progression-free survival (PFS) of pirtobrutinib plus venetoclax and rituximab (Arm A) compared to venetoclax and rituximab (Arm B)
Timepoint [1] 0 0
Up to approximately 5 years
Secondary outcome [1] 0 0
To evaluate the efficacy of Arm A compared to Arm B: Progression-free survival (PFS)
Timepoint [1] 0 0
Up to approximately 5 years
Secondary outcome [2] 0 0
To evaluate the efficacy of Arm A compared to Arm B: Overall survival (OS)
Timepoint [2] 0 0
Up to approximately 5 years
Secondary outcome [3] 0 0
To evaluate the efficacy of Arm A compared to Arm B: Time to next treatment (TTNT)
Timepoint [3] 0 0
Up to approximately 5 years
Secondary outcome [4] 0 0
To evaluate the efficacy of Arm A compared to Arm B: Event-free survival (EFS)
Timepoint [4] 0 0
Up to approximately 5 years
Secondary outcome [5] 0 0
To evaluate the efficacy of Arm A compared to Arm B: Overall response rate (ORR)
Timepoint [5] 0 0
Up to approximately 5 years
Secondary outcome [6] 0 0
To evaluate the effectiveness of Arm A compared to Arm B in patient-reported disease-related symptoms
Timepoint [6] 0 0
Up to approximately 5 years
Secondary outcome [7] 0 0
To evaluate the effectiveness of Arm A compared to Arm B in patient-reported physical functioning
Timepoint [7] 0 0
Up to approximately 5 years

Eligibility
Key inclusion criteria
- Confirmed diagnosis of CLL/SLL requiring therapy per iwCLL 2018 criteria

- Previous treatment with at least one line of therapy that may include a covalent
Bruton's tyrosine kinase (BTK) inhibitor

- Platelets greater than or equal to (=)50 x 10?/liter (L), hemoglobin =8
grams/deciliter (g/dL) and absolute neutrophil count =1.0 x 10?/L

- Adequate organ function

- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2

- Estimated creatinine clearance =30 milliliters per minute (mL/min)
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Known or suspected Richter's transformation at any time preceding enrollment

- Prior therapy with a non-covalent (reversible) BTK inhibitor

- Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K
antagonist

- Current treatment with strong cytochrome P450 (CYP) 3A4 (CYP3A4) inhibitors or
inducers

- Prior therapy with venetoclax

- Central nervous system (CNS) involvement

- Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection

- Known human immunodeficiency virus (HIV) infection, regardless of cluster of
differentiation 4 (CD4) count

- Allogeneic stem cell transplantation (SCT) or chimeric antigen receptor (CAR)-T within
60 days

- Active hepatitis B or hepatitis C

- Known active cytomegalovirus (CMV) infection

- Uncontrolled immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia
(AIHA)

- Significant cardiovascular disease

- Vaccination with a live vaccine within 28 days prior to randomization

- Patients with the following hypersensitivity:

- Known hypersensitivity to any component or excipient of pirtobrutinib and
venetoclax

- Prior significant hypersensitivity to rituximab

- Known allergy to allopurinol and inability to take uric acid lowering agent

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
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
20/09/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/01/2027
Actual
Sample size
Target
600
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,TAS,VIC,WA
Recruitment hospital [1] 0 0
Border Medical Oncology - Albury
Recruitment hospital [2] 0 0
Concord Repatriation General Hospital - Concord
Recruitment hospital [3] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [4] 0 0
Flinders Medical Centre - Adelaide
Recruitment hospital [5] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [6] 0 0
St. Vincent's Hospital - Fitzroy
Recruitment hospital [7] 0 0
Peninsula Private Hospital - Frankston
Recruitment hospital [8] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [9] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [10] 0 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2640 - Albury
Recruitment postcode(s) [2] 0 0
2139 - Concord
Recruitment postcode(s) [3] 0 0
5000 - Adelaide
Recruitment postcode(s) [4] 0 0
5042 - Adelaide
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7000 - Hobart
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3065 - Fitzroy
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3199 - Frankston
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
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6150 - Murdoch
Recruitment postcode(s) [10] 0 0
6009 - Nedlands
Recruitment outside Australia
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North Carolina
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Ohio
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Gent
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Pomorskie
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Lódz
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Singapore
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Singapore
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Asturias
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Castilla La Mancha
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Madrid
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Malaga
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Barcelona
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Sevilla
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Spain
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Valencia
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Sweden
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Lund
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Stockholm
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Uppsala
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Switzerland
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Ticino
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Luzern
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Taoyuan City
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Taipei
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Devon
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England
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West Midlands
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United Kingdom
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West Yorkshire
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Oxford
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United Kingdom
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Surrey

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
The purpose of this study is to compare the efficacy and safety of fixed duration
pirtobruitinib (LOXO-305) with VR (Arm A) compared to VR alone (Arm B) in patients with
CLL/SLL who have been previously treated with at least one prior line of therapy.
Participation could last up to five years.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04965493
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James Pauff, MD
Address 0 0
Loxo Oncology
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Patient Advocacy
Address 0 0
Country 0 0
Phone 0 0
1-855-LOXO-305
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT04965493