Trial Review

Please note the ANZCTR will be unattended from Friday 20 December 2024 for the holidays. The Registry will re-open on Tuesday 7 January 2025. Submissions and updates will not be processed during that time.

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/NCT04666038




Registration number
NCT04666038
Ethics application status
Date submitted
7/12/2020
Date registered
14/12/2020
Date last updated
29/10/2024

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
Recruitment hospital [2] 0 0
St Vincent's Hospital - Darlinghurst
Recruitment hospital [3] 0 0
The St. George Hospital - Kogarah
Recruitment hospital [4] 0 0
Ingham Institute of Medical Research - Liverpool
Recruitment hospital [5] 0 0
Westmead Hospital - Wentworthville
Recruitment hospital [6] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [7] 0 0
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
Recruitment postcode(s) [4] 0 0
NSW2170 - Liverpool
Recruitment postcode(s) [5] 0 0
2145 - Wentworthville
Recruitment postcode(s) [6] 0 0
3004 - Melbourne
Recruitment postcode(s) [7] 0 0
6000 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
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
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Illinois
Country [9] 0 0
United States of America
State/province [9] 0 0
Indiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Kentucky
Country [11] 0 0
United States of America
State/province [11] 0 0
Louisiana
Country [12] 0 0
United States of America
State/province [12] 0 0
Maryland
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Minnesota
Country [15] 0 0
United States of America
State/province [15] 0 0
Montana
Country [16] 0 0
United States of America
State/province [16] 0 0
Nebraska
Country [17] 0 0
United States of America
State/province [17] 0 0
New Jersey
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
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
South Carolina
Country [22] 0 0
United States of America
State/province [22] 0 0
Texas
Country [23] 0 0
United States of America
State/province [23] 0 0
Virginia
Country [24] 0 0
United States of America
State/province [24] 0 0
Washington
Country [25] 0 0
United States of America
State/province [25] 0 0
Wisconsin
Country [26] 0 0
Austria
State/province [26] 0 0
Oberösterreich
Country [27] 0 0
Austria
State/province [27] 0 0
Osterreich
Country [28] 0 0
Austria
State/province [28] 0 0
Wien
Country [29] 0 0
Belgium
State/province [29] 0 0
Liege
Country [30] 0 0
Belgium
State/province [30] 0 0
Oost-Vlaanderen
Country [31] 0 0
Belgium
State/province [31] 0 0
West Flanders
Country [32] 0 0
Belgium
State/province [32] 0 0
Gent
Country [33] 0 0
Belgium
State/province [33] 0 0
Haine-Saint-Paul
Country [34] 0 0
Belgium
State/province [34] 0 0
Herentals
Country [35] 0 0
Belgium
State/province [35] 0 0
Ottignies
Country [36] 0 0
Canada
State/province [36] 0 0
Manitoba
Country [37] 0 0
Canada
State/province [37] 0 0
Nova Scotia
Country [38] 0 0
Canada
State/province [38] 0 0
Ontario
Country [39] 0 0
China
State/province [39] 0 0
Beijing
Country [40] 0 0
China
State/province [40] 0 0
Gansu
Country [41] 0 0
China
State/province [41] 0 0
Guangdong
Country [42] 0 0
China
State/province [42] 0 0
Hainan
Country [43] 0 0
China
State/province [43] 0 0
Henan
Country [44] 0 0
China
State/province [44] 0 0
Hunan
Country [45] 0 0
China
State/province [45] 0 0
Jiangsu
Country [46] 0 0
China
State/province [46] 0 0
Jiangxi
Country [47] 0 0
China
State/province [47] 0 0
Tianjin
Country [48] 0 0
China
State/province [48] 0 0
Xinjiang
Country [49] 0 0
China
State/province [49] 0 0
Zhejiang
Country [50] 0 0
China
State/province [50] 0 0
Shanghai
Country [51] 0 0
Croatia
State/province [51] 0 0
Split
Country [52] 0 0
Croatia
State/province [52] 0 0
Zagreb
Country [53] 0 0
Czechia
State/province [53] 0 0
Brno
Country [54] 0 0
Czechia
State/province [54] 0 0
Hradec Kralove
Country [55] 0 0
Czechia
State/province [55] 0 0
Praha 2
Country [56] 0 0
France
State/province [56] 0 0
Cedex 09
Country [57] 0 0
France
State/province [57] 0 0
Cedex
Country [58] 0 0
France
State/province [58] 0 0
La Roche Sur Yon
Country [59] 0 0
France
State/province [59] 0 0
Nimes
Country [60] 0 0
France
State/province [60] 0 0
Seine-Maritime
Country [61] 0 0
France
State/province [61] 0 0
Tours Cedex 9
Country [62] 0 0
France
State/province [62] 0 0
Bayonne
Country [63] 0 0
France
State/province [63] 0 0
Bordeaux
Country [64] 0 0
France
State/province [64] 0 0
Brest cedex
Country [65] 0 0
France
State/province [65] 0 0
Le Mans
Country [66] 0 0
France
State/province [66] 0 0
Lille cedex
Country [67] 0 0
France
State/province [67] 0 0
Perpignan
Country [68] 0 0
France
State/province [68] 0 0
Politiers
Country [69] 0 0
Germany
State/province [69] 0 0
Baden-Württemberg
Country [70] 0 0
Germany
State/province [70] 0 0
Köln
Country [71] 0 0
Germany
State/province [71] 0 0
Mainz
Country [72] 0 0
Germany
State/province [72] 0 0
München
Country [73] 0 0
Germany
State/province [73] 0 0
Schleswig-Holstein
Country [74] 0 0
Germany
State/province [74] 0 0
Berlin
Country [75] 0 0
Hungary
State/province [75] 0 0
Budapest
Country [76] 0 0
Hungary
State/province [76] 0 0
Debrecen
Country [77] 0 0
Hungary
State/province [77] 0 0
Nyiregyhaza
Country [78] 0 0
Hungary
State/province [78] 0 0
Pecs
Country [79] 0 0
Ireland
State/province [79] 0 0
Dublin 7
Country [80] 0 0
Ireland
State/province [80] 0 0
Dublin 8
Country [81] 0 0
Ireland
State/province [81] 0 0
Dublin
Country [82] 0 0
Israel
State/province [82] 0 0
HaMerkaz
Country [83] 0 0
Israel
State/province [83] 0 0
Beer Sheva
Country [84] 0 0
Israel
State/province [84] 0 0
Netanya
Country [85] 0 0
Israel
State/province [85] 0 0
Tel Aviv
Country [86] 0 0
Israel
State/province [86] 0 0
?eifa
Country [87] 0 0
Italy
State/province [87] 0 0
Bari
Country [88] 0 0
Italy
State/province [88] 0 0
Piano 2
Country [89] 0 0
Italy
State/province [89] 0 0
PI
Country [90] 0 0
Italy
State/province [90] 0 0
Potenza
Country [91] 0 0
Italy
State/province [91] 0 0
Veneto
Country [92] 0 0
Italy
State/province [92] 0 0
Alessandria
Country [93] 0 0
Italy
State/province [93] 0 0
Bergamo
Country [94] 0 0
Italy
State/province [94] 0 0
Brescia
Country [95] 0 0
Italy
State/province [95] 0 0
Catania
Country [96] 0 0
Italy
State/province [96] 0 0
Catanzaro
Country [97] 0 0
Italy
State/province [97] 0 0
Firenze
Country [98] 0 0
Italy
State/province [98] 0 0
Genova
Country [99] 0 0
Italy
State/province [99] 0 0
Messina
Country [100] 0 0
Italy
State/province [100] 0 0
Milano
Country [101] 0 0
Italy
State/province [101] 0 0
Modena
Country [102] 0 0
Italy
State/province [102] 0 0
Pavia
Country [103] 0 0
Italy
State/province [103] 0 0
Perugia
Country [104] 0 0
Italy
State/province [104] 0 0
Ravenna
Country [105] 0 0
Italy
State/province [105] 0 0
Roma
Country [106] 0 0
Italy
State/province [106] 0 0
Terni
Country [107] 0 0
Italy
State/province [107] 0 0
Torino
Country [108] 0 0
Italy
State/province [108] 0 0
Tricase
Country [109] 0 0
Italy
State/province [109] 0 0
Trieste
Country [110] 0 0
Italy
State/province [110] 0 0
Verona
Country [111] 0 0
Japan
State/province [111] 0 0
Aichi
Country [112] 0 0
Japan
State/province [112] 0 0
Gifu
Country [113] 0 0
Japan
State/province [113] 0 0
Hokkaido
Country [114] 0 0
Japan
State/province [114] 0 0
Hyogo
Country [115] 0 0
Japan
State/province [115] 0 0
Kanagawa
Country [116] 0 0
Japan
State/province [116] 0 0
Kochi
Country [117] 0 0
Japan
State/province [117] 0 0
Miyagi-Ken
Country [118] 0 0
Japan
State/province [118] 0 0
Miyagi
Country [119] 0 0
Japan
State/province [119] 0 0
Osaka
Country [120] 0 0
Japan
State/province [120] 0 0
Saitama
Country [121] 0 0
Japan
State/province [121] 0 0
Tokyo
Country [122] 0 0
Japan
State/province [122] 0 0
Fukoka-ken
Country [123] 0 0
Japan
State/province [123] 0 0
Kumamoto
Country [124] 0 0
Japan
State/province [124] 0 0
Okayama
Country [125] 0 0
Korea, Republic of
State/province [125] 0 0
Incheon-gwangyeoksi [Incheon]
Country [126] 0 0
Korea, Republic of
State/province [126] 0 0
Pusan-Kwangyokshi
Country [127] 0 0
Korea, Republic of
State/province [127] 0 0
Seoul, Korea
Country [128] 0 0
Korea, Republic of
State/province [128] 0 0
Seoul-teukbyeolsi [Seoul]
Country [129] 0 0
Korea, Republic of
State/province [129] 0 0
Seoul
Country [130] 0 0
Korea, Republic of
State/province [130] 0 0
Busan
Country [131] 0 0
Poland
State/province [131] 0 0
Legnica
Country [132] 0 0
Poland
State/province [132] 0 0
Lubelskie
Country [133] 0 0
Poland
State/province [133] 0 0
Pomorskie
Country [134] 0 0
Poland
State/province [134] 0 0
Brzozów
Country [135] 0 0
Poland
State/province [135] 0 0
Bydgoszcz
Country [136] 0 0
Poland
State/province [136] 0 0
Katowice
Country [137] 0 0
Poland
State/province [137] 0 0
Krakow
Country [138] 0 0
Poland
State/province [138] 0 0
Walbrzych
Country [139] 0 0
Poland
State/province [139] 0 0
Warszawa
Country [140] 0 0
Poland
State/province [140] 0 0
Wroclaw
Country [141] 0 0
Poland
State/province [141] 0 0
Lódz
Country [142] 0 0
Russian Federation
State/province [142] 0 0
Omskaya Oblast'
Country [143] 0 0
Russian Federation
State/province [143] 0 0
Saint Petersburg
Country [144] 0 0
Russian Federation
State/province [144] 0 0
Sochi
Country [145] 0 0
Singapore
State/province [145] 0 0
Central Singapore
Country [146] 0 0
Spain
State/province [146] 0 0
Barcelona
Country [147] 0 0
Spain
State/province [147] 0 0
Castilla La Mancha
Country [148] 0 0
Spain
State/province [148] 0 0
La Coruna
Country [149] 0 0
Spain
State/province [149] 0 0
Madrid, Comunidad De
Country [150] 0 0
Spain
State/province [150] 0 0
Madrid
Country [151] 0 0
Spain
State/province [151] 0 0
Planta Baja
Country [152] 0 0
Spain
State/province [152] 0 0
Albacete
Country [153] 0 0
Spain
State/province [153] 0 0
Caceres
Country [154] 0 0
Spain
State/province [154] 0 0
Santander
Country [155] 0 0
Spain
State/province [155] 0 0
Sevilla
Country [156] 0 0
Spain
State/province [156] 0 0
Vitoria
Country [157] 0 0
Switzerland
State/province [157] 0 0
Svizzera
Country [158] 0 0
Taiwan
State/province [158] 0 0
Taichung
Country [159] 0 0
Taiwan
State/province [159] 0 0
Taipei
Country [160] 0 0
Taiwan
State/province [160] 0 0
Taipei City
Country [161] 0 0
Taiwan
State/province [161] 0 0
Taoyuan, (r.o.c.)
Country [162] 0 0
Turkey
State/province [162] 0 0
Ankara
Country [163] 0 0
Turkey
State/province [163] 0 0
Istanbul
Country [164] 0 0
Turkey
State/province [164] 0 0
Melikgazi
Country [165] 0 0
Turkey
State/province [165] 0 0
Yenimahalle
Country [166] 0 0
Turkey
State/province [166] 0 0
Izmir
Country [167] 0 0
United Kingdom
State/province [167] 0 0
Aberdeen City
Country [168] 0 0
United Kingdom
State/province [168] 0 0
Cornwall
Country [169] 0 0
United Kingdom
State/province [169] 0 0
Devon
Country [170] 0 0
United Kingdom
State/province [170] 0 0
East Yorkshire
Country [171] 0 0
United Kingdom
State/province [171] 0 0
Greater London
Country [172] 0 0
United Kingdom
State/province [172] 0 0
Norfolk
Country [173] 0 0
United Kingdom
State/province [173] 0 0
Sa2 8qa
Country [174] 0 0
United Kingdom
State/province [174] 0 0
Scotland
Country [175] 0 0
United Kingdom
State/province [175] 0 0
Surrey
Country [176] 0 0
United Kingdom
State/province [176] 0 0
West Lothian
Country [177] 0 0
United Kingdom
State/province [177] 0 0
Leeds
Country [178] 0 0
United Kingdom
State/province [178] 0 0
Milton Keynes
Country [179] 0 0
United Kingdom
State/province [179] 0 0
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
Trial website
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

No information has been provided regarding IPD availability


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/NCT04666038