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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/NCT04666038




Registration number
NCT04666038
Ethics application status
Date submitted
7/12/2020
Date registered
14/12/2020
Date last updated
26/04/2024

Titles & IDs
Public title
Study of LOXO-305 Versus Investigator's Choice (IdelaR or BR) in Patients With Previously Treated Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
Scientific title
A Phase 3 Open-Label, Randomized Study of LOXO-305 Versus Investigator's Choice of Idelalisib Plus Rituximab or Bendamustine Plus Rituximab in BTK Inhibitor Pretreated Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN CLL-321)
Secondary ID [1] 0 0
J2N-OX-JZNN
Secondary ID [2] 0 0
LOXO-BTK-20020
Universal Trial Number (UTN)
Trial acronym
BRUIN CLL-321
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 - LOXO-305
Treatment: Drugs - Idelalisib
Treatment: Drugs - Bendamustine
Treatment: Drugs - Rituximab

Experimental: Arm A (LOXO-305) - Orally

Active Comparator: Arm B (Idelalisib plus rituximab [IdelaR] or bendamustine plus rituximab [BR]) - Investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR).


Treatment: Drugs: LOXO-305
Oral LOXO-305

Treatment: Drugs: Idelalisib
Oral

Treatment: Drugs: Bendamustine
IV

Treatment: Drugs: Rituximab
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 LOXO-305 monotherapy (Arm A) compared to investigator's choice of idelalisib plus rituximab (IdelaR) or bendamustine plus rituximab (BR) (Arm B)
Timepoint [1] 0 0
Up to approximately 36 months
Secondary outcome [1] 0 0
To evaluate the effectiveness of Arm A compared to Arm B based on Overall Response Rate (ORR)
Timepoint [1] 0 0
Up to approximately 36 months
Secondary outcome [2] 0 0
To evaluate the effectiveness of Arm A compared to Arm B based on Overall Survival (OS)
Timepoint [2] 0 0
Up to approximately 36 months
Secondary outcome [3] 0 0
To evaluate the effectiveness of Arm A compared to Arm B based on Time to Next Treatment (TTNT)
Timepoint [3] 0 0
Up to approximately 36 months
Secondary outcome [4] 0 0
Time to worsening (TTW) of CLL/SLL related symptoms
Timepoint [4] 0 0
Up to approximately 36 months
Secondary outcome [5] 0 0
Time to worsening (TTW) of physical function
Timepoint [5] 0 0
Up to approximately 36 months

Eligibility
Key inclusion criteria
- Confirmed diagnosis of CLL/SLL requiring therapy as defined by iwCLL 2018 criteria.

- Previously treated with a covalent BTK inhibitor.

- Eastern Cooperative Oncology Group (ECOG) 0-2.

- Absolute neutrophil count = 0.75 × 10^9/L without granulocyte-colony-stimulating
factor support, or = 0.50 × 10^9/L in patients with documented bone marrow involvement
considered to impair hematopoiesis. Granulocyte-colony-stimulating factor support is
permitted in patients with documented bone marrow involvement.

- Hemoglobin = 8 g/dL or = 6 g/dL in patients with documented bone marrow involvement
considered to impair hematopoiesis. Transfusion support is permitted in patients with
bone marrow involvement.

- Platelets = 50 × 10^9/L. If an investigator has chosen bendamustine/rituximab as the
Arm B treatment, platelets must be = 75 × 10^9/L. Patients may enroll below these
thresholds if the Investigator determines the cytopenia is related to bone marrow
involvement considered to impair hematopoiesis. Patients with a platelet count < 30 x
10^9/L are excluded.

- AST and ALT = 3.0 x upper limit of normal (ULN).

- Total bilirubin = 1.5 x ULN.

- Estimated creatinine clearance of = 30 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.

- Known or suspected history of central nervous system (CNS) involvement by CLL/SLL.

- Ongoing drug-induced liver injury.

- Active uncontrolled auto-immune cytopenia.

- Significant cardiovascular disease.

- History of allogeneic or stem cell transplantation (SCT) or chimeric antigen
receptor-modified T cells (CAR-T) therapy within the past 60 days.

- Active hepatitis B or hepatitis C.

- Known active cytomegalovirus (CMV) infection.

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

- Known Human Immunodeficiency Virus (HIV) infection, regardless of CD4 count.

- Clinically significant active malabsorption syndrome or inflammatory bowel disease

- Prior exposure to 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.

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

- Patients with the following hypersensitivity:

1. Known hypersensitivity, including anaphylaxis, to any component or excipient of
LOXO-305. For patients planned to receive idelalisib, known hypersensitivity,
including anaphylaxis, to any component or excipient of idelalisib. For patients
planned to receive bendamustine, known hypersensitivity, including anaphylaxis,
to any component or excipient of bendamustine.

2. Prior significant hypersensitivity to rituximab.

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
9/03/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/05/2027
Actual
Sample size
Target
250
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,VIC,WA
Recruitment hospital [1] 0 0
Canberra Hospital - Garran
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St Vincent's Hospital - Darlinghurst
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The St. George Hospital - Kogarah
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Ingham Institute of Medical Research - Liverpool
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Westmead Hospital - Wentworthville
Recruitment hospital [6] 0 0
The Alfred Hospital - Melbourne
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Royal Perth Hospital - Perth
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2217 - Kogarah
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NSW2170 - Liverpool
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2145 - Wentworthville
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
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6000 - Perth
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Ankara
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Istanbul
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Melikgazi
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Izmir
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Leeds
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Milton Keynes
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Newmarket

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 patients with chronic lymphocytic leukemia (CLL) or small lymphocytic
leukemia (SLL) who have previously received treatment with at least a BTK inhibitor. The main
purpose is to compare LOXO-305 to idelalisib plus rituximab or bendamustine plus rituximab.
Participation could last up to four years, and possibly longer, if the disease does not
progress.
Trial website
https://clinicaltrials.gov/ct2/show/NCT04666038
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Marisa Hill, MD
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/NCT04666038