Chronic Lymphocytic LeukemiaPhase 3BRUIN-CLL-313NCT05023980
A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)
A Phase 3 study testing Pirtobrutinib, Bendamustine and Rituximab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Loxo Oncology, Inc. at 108 sites in 20 countries.
Trial summary
The purpose of this study is to compare the efficacy and safety of pirtobrutinib (LOXO-305; Arm A) compared to BR (Arm B) in patients with CLL/SLL who have not been treated. Participation could last up to five years. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
- What is being tested?
- Pirtobrutinib, Bendamustine and Rituximab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 282 participants
- Where
- 108 sitesin 20 countries
- Study dates
- 23 Sep 2021to Oct 2027
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Confirmed diagnosis of CLL/SLL requiring therapy, per iwCLL 2018 criteria
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Adequate organ function
- Platelets greater than or equal to (≥)75 x 10⁹/liter (L) (≥50 × 10⁹/L for patients with evidence of bone marrow infiltrate), hemoglobin ≥8 grams/deciliter (g/dL), and absolute neutrophil count ≥0.75 x 10⁹/L
- Kidney function: Estimated creatinine clearance ≥40 milliliters per minute (mL/min)
Who cannot join
- Known or suspected Richter's transformation at any time preceding enrollment
- Prior systemic therapy for CLL/SLL
- Presence of 17p deletion
- Central nervous system (CNS) involvement
- Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP])
- Significant cardiovascular disease
Show all 16Show fewer
- Active hepatitis B or hepatitis C
- Active cytomegalovirus (CMV) infection
- Active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
- Known human immunodeficiency virus (HIV) infection, regardless of cluster of differentiation 4 (CD4) count
- Concurrent use of investigational agent or anticancer therapy except hormonal therapy
- Patients requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist
- Vaccination with a live vaccine within 28 days prior to randomization
- Patients with the following hypersensitivity:
- Known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or bendamustine
- Prior significant hypersensitivity to rituximab
Trial locations and contacts
108 sites in 20 countries.
108 sites in 20 countries
China19 sites
Peking University First Hospital
Beijing, Beijing Municipality, 100034
Peking University Third Hospital
Beijing, Beijing Municipality, 100191
Beijing Hospital
Beijing, 100730
Shanghai Tongren Hospital
Changning District, Shanghai Municipality, 200050
Xiangya Hospital Central South University
Changsha, Hunan, 410008
Hunan Cancer Hospital
Changsha, Hunan, 410013
West China Hospital of Sichuan University
Chengdu, Sichuan, 610041
Chongqing Cancer Hospital
Chongqing, 400030
The First Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510120
The First People's Hospital of Hangzhou Linping District
Hangzhou, Zhejiang, 311100
Anhui Provincial Cancer Hospital
Hefei, Anhui, 233004
The Affiliated Hospital of Inner Mongolia Medical University
Hohhot, Inner Mongolia, 010050
The First Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006
Jiangsu Province Hospital
Nanjing, Nanjing, 210029
Shengjing Hospital of China Medical University
Shenyany, Liaoning, 110022
Institute of hematology&blood disease hospital
Tianjin, Tianjin Municipality, 300020
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, 300060
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, Hubei, 430022
Henan Cancer Hospital
Zhengzhou, 450008
Italy12 sites
Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII
Bergamo, 24127
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia
Brescia, 25123
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
Meldola, 47014
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
Milan, 20122
ASST Grande Ospedale Metropolitano Niguarda Comitato Etico Milano Area C
Milan, 20162
Azienda Socio Sanitaria Territoriale di Monza (Presidio San Gerardo)
Monza, 20900
Azienda Ospedale Maggiore Della Carita
Novara, 28100
Istituto di Ematologia-C.R.E.O. (Centro di Ricerche Emato-Oncologich)
Perugia, 06132
Ospedale Santa Maria delle Croci
Ravenna, 48020
Irccs Crob
Rionero in Vulture, Potenza, 85028
Azienda Ospedaliera Santa Maria Terni
Terni, 05100
Azienda sanitaria integrata università di Trieste
Trieste, 34125
Poland12 sites
KO-MED Centra Kliniczne
Biała Podlaska, 21500
Szpital Uniwersytecki nr 1 im. Antoniego Jurasza
Bydgoszcz, 85-168
Uniwersyteckie Centrum Kliniczne
Gdansk, Pomeranian Voivodeship, 80214
Wojewodzki Szpital Specjalistyczny
Iwaszkiewicza 5, Legnica, 59-220
Pratia Onkologia Katowice
Katowice, 40519
Pratia MCM Krakow
Krakow, 30727
Klinika Hematoonkologii i Transplantacji Szpiku SPSK1 Lublin
Lublin, Lubelskie V, 20081
Centrum Onkologii Ziemi Lubelskiej
Lublin, 20-090
Centrum Medyczne Pratia Poznan
Skorzewo, Poznan, 60 185
Nasz Lekarz Osrodek Badan Klinicznych
Torun, 87-100
Narodowy Instytut Onkologii im. Marii Skłodowskiej-Cuire - Państwowy Instytut Badawczy
Warsaw, 02781
Uniwersytecki Szpital Kliniczny Klinika
Wroclaw, 50-367
Japan11 sites
Aomori Prefectural Centeral Hospital
Aomori, 030-8553
Chiba Cancer Center
Chiba, Chiba, 260-8717
University of Yamanashi Hospital
Chūō, Yamanshi, 409-3821
JCHO Kyushu Hospital
Fukoka-ken, 806 8501
Dokkyo Medical University - Koshigaya Hospital
Koshigaya, Saitama, 343 8555
Nagoya City University Hospital
Nagoya, Aichi-ken, 467-8602
Kochi Medical School Hospital
Nankoku, Kochi, 783-8505
Hokuyukai Sapporo Hokuyu Hospital
Sapporo, Hokkaido, 0030006
Tohoku University Hospital
Sendai, Miyagi, 980-8574
NHO Sendai Medical Center
Sendai, Miyagi, 9838520
Fukui Medical University Hospital
Yoshida-Gun, Fukui, 910-1193
South Korea6 sites
Inje Univ Busan Paik Hospital
Busan, 47392
Gachon University Gil Medical Center
Namdong-gu, Incheon-gwangyeoksi [Incheon], 21565
The Catholic University of Korea-Seoul St. Mary's Hospital
Seocho-Gu, Seoul, 06591
Seoul National University Hospital
Seoul, Seoul, Korea, 03080
Severance Hospital, Yonsei University Health System
Seoul, Seoul-teukbyeolsi [Seoul], 03722
Samsung Medical Center
Seoul, Seoul-teukbyeolsi [Seoul], 06351
Spain6 sites
Hospital de la Santa Creu i Sant Pau
Barcelona, 08041
Hospital Universitario HM Sanchinarro
Madrid, Madrid, Comunidad de, 28050
Hospital Universitario Fundación Jiménez Díaz
Madrid, 28040
Hospital Universitario Central de Asturias
Oviedo, Principality of Asturias, 33011
Hospital Universitario Virgen del Rocío
Seville, 41013
Hospital Universitario Virgen de Valme
Seville, 41014
United States5 sites
New Jersey Center for Cancer Research
Brick, New Jersey, 08724
Oncology-Hematology Associates of West Broward
Coral Springs, Florida, 33065
California Research Institute
Los Angeles, California, 90027
Clinical Research Alliance, Inc.
Westbury, New York, 11590
Innovative Clinical Research Institute
Whittier, California, 90603
Brazil5 sites
Hemocentro Unicamp
Campinas, São Paulo, 13083-878
Fundação Doutor Amaral Carvalho
Jaú, São Paulo, 17210120
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903
Irmandade da Santa Casa de Misericórdia de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90050-170
Centro Gaucho Integrado - Mae de Deus Center
Porto Alegre, Rio Grande do Sul, 90110270
Bulgaria4 sites
UMHAT "Sveti Georgi" EAD
Plovdiv, 4000
UMHAT 'Sv. Ivan Rilski', EAD
Sofia, 1431
"SHATHD" EAD, Sofia
Sofia, 1797
UMHAT - Prof. Dr. Stoyan Kirkovich" AD
Stara Zagora, 6003
New Zealand4 sites
Christchurch Hospital
Christchurch, 8011
Middlemore Clinical Trials
Papatoetoe, 2025
North Shore Hospital, Haematology Research
Takapuna, Auckland, 0622
Tauranga Hospital
Tauranga, Bay of Plenty, 3112
Romania4 sites
Institutul Clinic Fundeni - Centrul de Hematologie si Transplant Medular
Bucharest, 022328
Institutul Oncologic "Prof. Dr. Ion Chiricuta" Cluj-Napoca
Cluj-Napoca, 400015
Spitalul Clinic Municipal Filantropia Craiova
Craiova, Dolj, 200143
Institutului Regional de Oncologie IASI
Iași, 700483
Taiwan4 sites
Chang Bing Show Chwan Memorial Hospital
Changhua, 50544
China Medical University Hospital
Taichung, 40447
National Taiwan University Hospital
Taipei, 10002
Chang Gung Memorial Hospital - Linkou
Taoyuan City, 333
Australia3 sites
Peninsula Private Hospital
Frankston, Victoria, 3199
Liverpool Hospital
Liverpool, New South Wales, 2170
Westmead Hospital
Wentworthville, New South Wales, 2145
Hungary3 sites
Debreceni Egyetem Orvos-es Egészsegtudomanyi Centrum
Debrecen, 4032
SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz
Nyíregyháza, 4400
Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
Székesfehérvár, 8000
Portugal3 sites
Centro Clínico Académico - Braga (2CA-Braga) (Hospital de Braga)
Braga, 4710-243
Centro Hospitalar de Lisboa Norte, E.P.E. - Hospital de Santa Maria
Lisbon, 1649035
Instituto Português de Oncologia do Porto Francisco Gentil, EPE
Porto, 4200-072
Austria2 sites
Uniklinikum Salzburg
Salzburg, 5020
Klinik Ottakring
Vienna, 1160
Czechia2 sites
Fakultni nemocnice Brno
Brno, 62500
Fakultni nemocnice Hradec Kralove
Hradec Králové, 500 05
Russia1 site
Academician I.P. Pavlov First St-Petersburg State Medical University
Saint Petersburg, 197022
United Kingdom1 site
Birmingham Heartlands Hospital
Birmingham, England, B9 5SS
About this study
Official title: A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
The purpose of this study is to compare the efficacy and safety of pirtobrutinib (LOXO-305; Arm A) compared to BR (Arm B) in patients with CLL/SLL who have not been treated. Participation could last up to five years.
- Being tested
- Pirtobrutinib, Bendamustine, Rituximab
- Keywords
- BTKi, BTK Inhibitor, Hematologic Disease, Lymphoma, non-Hodgkin's, Lymphoma, B-cell
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Hematologic Diseases, Lymphoma, Non-Hodgkin, Lymphoma, B-Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PirtobrutinibDrug
Also called LOXO-305, LY3527727
Oral
BendamustineDrug
Also called Treanda, Treakisym, Ribomustin, Levact
IV
RituximabDrug
Also called Rituxan, MabThera, Truxima, Riabni
IV
| Study group | Role | What they receive |
|---|---|---|
| Arm A - Pirtobrutinib | Experimental | Participants received pirtobrutinib 200 milligrams (mg) orally once daily in continuous 28-day cycles until disease progression or unacceptable toxicity. Receives: Drug: Pirtobrutinib |
| Arm B - Bendamustine Plus Rituximab | Active comparator | Participants received bendamustine 90 milligrams per square meter (mg/m²) intravenously on Days 1 and 2 of each 28-day cycle (Cycles 1-6) plus rituximab 375 mg/m² intravenously on Cycle 1 Day 1, then 500 mg/m² on Day 1 of Cycles 2-6. Eligible participants in Arm B crossed over to receive pirtobrutinib following independent review committee (IRC)-confirmed progressive disease (PD). Receives: Drug: Bendamustine; Drug: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Arm A Compared to Arm B: Progression-free Survival (PFS), Assessed by Independent Review Committee (IRC)
PFS, as assessed by IRC, is defined as the time from randomization until documented disease progression as per iwCLL (International Workshop on Chronic Lymphocytic Leukemia) 2018 criteria, or death from any cause, whichever occurs first.
Measured: From randomization until documented disease progression or death (up to 40 months)
Secondary outcomes (9)
Arm A Compared to Arm B: Progression-free Survival (PFS), Assessed by Investigator
PFS, as assessed by investigator, is defined as the time from randomization until documented disease progression as per iwCLL (International Workshop on Chronic Lymphocytic Leukemia) 2018 criteria, or death from any cause, whichever occurs first.
Measured: From randomization until documented disease progression or death (up to 40 months)
To Evaluate the Effectiveness of Arm A Compared to Arm B: Overall Survival (OS)
Assessments of effectiveness include OS, assessed by investigator
Measured: Up to approximately 5 years
Arm A Compared to Arm B: Time to Next Treatment (TTNT), Assessed by Investigator
TTNT is defined as time from the date of randomization to the date of initiation of the subsequent anticancer therapy for Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) including the first dose date of pirtobrutinib for Arm B participants who crossed over to receive pirtobrutinib if applicable or death due to any cause, whichever occurs first.
Measured: From randomization until initiation of the subsequent anticancer therapy or death (up to 41 months)
Arm A Compared to Arm B: Percentage of Participants With Overall Response (ORR), Assessed by IRC
ORR, as assessed by IRC, is defined as number of participants who achieved a best overall response of complete remission (CR), complete remission with an incomplete marrow recovery (CRi), nodular partial remission (nPR) or partial remission (PR) at or before the initiation of subsequent anticancer therapy, disease progression or death, divided by the total number of participants randomized to each treatment arm.
Measured: From randomization until subsequent anticancer therapy, disease progression or death (up to 40 months)
Arm A Compared to Arm B: Percentage of Participants With Overall Response (ORR), Assessed by Investigator
ORR, as assessed by investigator, is defined as number of participants who achieved a best overall response of complete remission (CR), complete remission with an incomplete marrow recovery (CRi), nodular partial remission (nPR) or partial remission (PR) at or before the initiation of subsequent anticancer therapy, disease progression or death, divided by the total number of participants randomized to each treatment arm.
Measured: From randomization until subsequent anticancer therapy, disease progression or death (up to 40 months)
Arm A Compared to Arm B: Duration of Response (DOR), Assessed by IRC
DoR, as assessed by IRC, is defined as the time from the date of the first documented response (CR, CRi, nPR, or PR) until the first date of the documentation of disease progression as per iwCLL 2018 criteria, or the date of death from any cause, whichever occurs first.
Measured: From first documented response until the first documented disease progression or death (up to 35 months)
Arm A Compared to Arm B: Duration of Response (DOR), Assessed by Investigator
DoR, as assessed by investigator, is defined as the time from the date of the first documented response (CR, CRi, nPR, or PR) until the first date of the documentation of disease progression as per iwCLL 2018 criteria, or the date of death from any cause, whichever occurs first.
Measured: From first documented response until the first documented disease progression or death (up to 35 months)
Arm A Compared to Arm B: Time to Worsening (TTW) of CLL/SLL-related Symptoms as Measured by the EORTC QLQ-C30 and IL-58
A measure of CLL/SLL-related symptoms (CLL/SLL-related Symptoms score) was derived from 13 items: appetite loss, fatigue (3 items), pain, nausea, dyspnea, and insomnia from the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), and night sweats, fever/chills, and fatigue (3 items) from selected items of the EORTC Item Library set 58 (IL-58). First, a raw score was calculated as mean of the item responses, then a linear transformation was applied to obtain standardized score ranging from 0 to 100, with higher score representing worse symptoms. TTW of CLL/SLL-related symptoms was defined as the time from randomization to the earliest date of the first sustained worsening in its score from baseline, meeting or exceeding the meaningful within-person change (MWPC) threshold of +5.12 points or death from any cause. Sustained worsening required that the threshold be met at two consecutive assessment timepoints.
Measured: From randomization up to 37 months
Arm A Compared to Arm B: Time to Worsening (TTW) of Physical Functioning as Measured by the Physical Function Domain of the EORTC-QLQ-C30
Physical Functioning was assessed with the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30) Physical Function (PF) scale consisting of 5 items to measure the impact of the disease and its treatment on a participant's ability to perform everyday physical activities, calculated from responses to the five items, each scored on a 4 point scale (1 = not at all to 4 = very much). First, a raw score was calculated as mean of the item responses, then a linear transformation was applied to obtain standardized score ranging from 0 to 100, with higher score representing better functioning. TTW of PF was defined as the time from randomization to the earliest date of the first sustained worsening from baseline, with a decline in the meaningful within-person change (MWPC) threshold of -13.33 points or death from any cause. Sustained worsening required that the threshold be met at two consecutive assessment timepoints.
Measured: From randomization up to 37 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2021
- Study start23 Sep 2021
- Primary completion11 Jul 2025
- Study completionOct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Chronic Lymphocytic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Eligible patients will be randomized 1:1 into Arm A and Arm B. Patients randomized to Arm B who have disease progression (PD) confirmed by independent review committee (IRC) may be eligible to crossover into Arm A.
- Masking
- None (open label)
- Enrolment
- 282 participants (actual)
Sponsor and investigators
- Lead sponsor
- Loxo Oncology, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Eli Lilly and Company
- Responsible party
- Sponsor
- Investigators
- Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05023980
- Sponsor's protocol ID
- 18088
- Other IDs
- J2N-OX-JZNP, LOXO-BTK-20023, 2024-511599-33-00
- Acronym
- BRUIN-CLL-313
- Status last verified
- Sep 2026
- First submitted
- 24 Aug 2021
- Last updated
- 25 Sep 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Eyre TA, Hess LM, Masoudi E, Jen MH, Abhyankar S, Graham-Clarke PL, Bhandari NR, Maguire P, Winfree KB, Tracey M, Taipale KL, Davids MS. Efficacy of Pirtobrutinib Monotherapy in Treatment-Naive Chronic Lymphocytic Leukemia: A Bayesian Network Meta-Analysis of Randomized Controlled Trials. Cancers (Basel). 2026 Feb 18;18(4):660. doi: 10.3390/cancers18040660.
PubMed 41749915Jurczak W, Kwiatek M, Czyz J, Roberto de Mattos E, Eom KS, Egle A, Panovska A, Popova ZG, Shih HJ, Casado Montero LF, Sportoletti P, Hua VM, D'Olimpio JT, Iida S, Ito R, Bao K, Fink A, Su W, Ruppert AS, Levy A, Wrobel T. BRUIN CLL-313: Randomized Phase III Trial of Pirtobrutinib Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. J Clin Oncol. 2026 Feb 20;44(6):466-475. doi: 10.1200/JCO-25-02380. Epub 2025 Dec 9.
PubMed 41363773
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
- ClinicalTrials.gov ID
- NCT05023980
- Acronym / sponsor ID
- BRUIN-CLL-313 / 18088
- Keywords
- BTKi, BTK Inhibitor, Hematologic Disease, Lymphoma, non-Hodgkin's, Lymphoma, B-cell
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 282 participants (actual)
- Lead sponsor
- Loxo Oncology, Inc.Industry (pharma, biotech, devices)
- Collaborators
- Eli Lilly and Company
- Study start
- 23 Sep 2021 (actual)
- Primary completion
- 11 Jul 2025 (actual)
- Study completion
- Oct 2027 (estimated)
- First posted
- 27 Aug 2021 (actual)
- Results
- Posted 25 Sep 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to compare the efficacy and safety of pirtobrutinib (LOXO-305; Arm A) compared to BR (Arm B) in patients with CLL/SLL who have not been treated. Participation could last up to five years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Eligible patients will be randomized 1:1 into Arm A and Arm B. Patients randomized to Arm B who have disease progression (PD) confirmed by independent review committee (IRC) may be eligible to crossover into Arm A.
| Arm | Type | Receives |
|---|---|---|
| Arm A - Pirtobrutinib | Experimental | Drug: PirtobrutinibParticipants received pirtobrutinib 200 milligrams (mg) orally once daily in continuous 28-day cycles until disease progression or unacceptable toxicity. |
| Arm B - Bendamustine Plus Rituximab | Active comparator | Drug: Bendamustine, Drug: RituximabParticipants received bendamustine 90 milligrams per square meter (mg/m²) intravenously on Days 1 and 2 of each 28-day cycle (Cycles 1-6) plus rituximab 375 mg/m² intravenously on Cycle 1 Day 1, then 500 mg/m² on Day 1 of Cycles 2-6. Eligible participants in Arm B crossed over to receive pirtobrutinib following independent review committee (IRC)-confirmed progressive disease (PD). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Confirmed diagnosis of CLL/SLL requiring therapy, per iwCLL 2018 criteria
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2
- Adequate organ function
- Platelets greater than or equal to (≥)75 x 10⁹/liter (L) (≥50 × 10⁹/L for patients with evidence of bone marrow infiltrate), hemoglobin ≥8 grams/deciliter (g/dL), and absolute neutrophil count ≥0.75 x 10⁹/L
- Kidney function: Estimated creatinine clearance ≥40 milliliters per minute (mL/min)
Key exclusion criteria (16 listed)
- Known or suspected Richter's transformation at any time preceding enrollment
- Prior systemic therapy for CLL/SLL
- Presence of 17p deletion
- Central nervous system (CNS) involvement
- Active uncontrolled auto-immune cytopenia (e.g., autoimmune hemolytic anemia [AIHA], idiopathic thrombocytopenic purpura [ITP])
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PirtobrutinibAlso: LOXO-305, LY3527727Oral | Drug | Arm A - Pirtobrutinib |
| BendamustineAlso: Treanda, Treakisym, Ribomustin, LevactIV | Drug | Arm B - Bendamustine Plus Rituximab |
| RituximabAlso: Rituxan, MabThera, Truxima, RiabniIV | Drug | Arm B - Bendamustine Plus Rituximab |
Primary outcome
Arm A Compared to Arm B: Progression-free Survival (PFS), Assessed by Independent Review Committee (IRC)
Time frame: From randomization until documented disease progression or death (up to 40 months)
PFS, as assessed by IRC, is defined as the time from randomization until documented disease progression as per iwCLL (International Workshop on Chronic Lymphocytic Leukemia) 2018 criteria, or death from any cause, whichever occurs first.
9 secondary outcomes
Arm A Compared to Arm B: Progression-free Survival (PFS), Assessed by Investigator
Time frame: From randomization until documented disease progression or death (up to 40 months)
To Evaluate the Effectiveness of Arm A Compared to Arm B: Overall Survival (OS)
Time frame: Up to approximately 5 years
Arm A Compared to Arm B: Time to Next Treatment (TTNT), Assessed by Investigator
Time frame: From randomization until initiation of the subsequent anticancer therapy or death (up to 41 months)
Arm A Compared to Arm B: Percentage of Participants With Overall Response (ORR), Assessed by IRC
Time frame: From randomization until subsequent anticancer therapy, disease progression or death (up to 40 months)
Arm A Compared to Arm B: Percentage of Participants With Overall Response (ORR), Assessed by Investigator
Time frame: From randomization until subsequent anticancer therapy, disease progression or death (up to 40 months)
Arm A Compared to Arm B: Duration of Response (DOR), Assessed by IRC
Time frame: From first documented response until the first documented disease progression or death (up to 35 months)
Arm A Compared to Arm B: Duration of Response (DOR), Assessed by Investigator
Time frame: From first documented response until the first documented disease progression or death (up to 35 months)
Arm A Compared to Arm B: Time to Worsening (TTW) of CLL/SLL-related Symptoms as Measured by the EORTC QLQ-C30 and IL-58
Time frame: From randomization up to 37 months
Arm A Compared to Arm B: Time to Worsening (TTW) of Physical Functioning as Measured by the Physical Function Domain of the EORTC-QLQ-C30
Time frame: From randomization up to 37 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 41749915Eyre TA, Hess LM, Masoudi E, Jen MH, Abhyankar S, Graham-Clarke PL, Bhandari NR, Maguire P, Winfree KB, Tracey M, Taipale KL, Davids MS. Efficacy of Pirtobrutinib Monotherapy in Treatment-Naive Chronic Lymphocytic Leukemia: A Bayesian Network Meta-Analysis of Randomized Controlled Trials. Cancers (Basel). 2026 Feb 18;18(4):660. doi: 10.3390/cancers18040660.
- Derived from this study: PubMed 41363773Jurczak W, Kwiatek M, Czyz J, Roberto de Mattos E, Eom KS, Egle A, Panovska A, Popova ZG, Shih HJ, Casado Montero LF, Sportoletti P, Hua VM, D'Olimpio JT, Iida S, Ito R, Bao K, Fink A, Su W, Ruppert AS, Levy A, Wrobel T. BRUIN CLL-313: Randomized Phase III Trial of Pirtobrutinib Versus Bendamustine Plus Rituximab in Untreated Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. J Clin Oncol. 2026 Feb 20;44(6):466-475. doi: 10.1200/JCO-25-02380. Epub 2025 Dec 9.
- A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (BRUIN CLL-313)Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) study director
Eli Lilly and Company
108 sites in 20 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Pirtobrutinib, Bendamustine and Rituximab in people with Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma, run by Loxo Oncology, Inc. at 108 sites in 20 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 108 sites in China, Italy, Poland, Japan, South Korea and 15 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 25 Sep 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Arm A Compared to Arm B: Progression-free Survival (PFS), Assessed by Independent Review Committee (IRC) (time frame: From randomization until documented disease progression or death (up to 40 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05023980, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.