NCT05023980 · CITED IN SOURCE DOCUMENTS

A Study of Pirtobrutinib (LOXO-305) Versus Bendamustine Plus Rituximab (BR) in Untreated Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.

Phase: PHASE3
Status at capture: ACTIVE NOT RECRUITING
Registry last update: 2026-09-25

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Arm A Compared to Arm B: Progression-free Survival (PFS), Assessed by Independent Review Committee (IRC)

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outcome · POSTED

Arm A Compared to Arm B: Progression-free Survival (PFS), Assessed by Investigator

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outcome · NOT POSTED

To Evaluate the Effectiveness of Arm A Compared to Arm B: Overall Survival (OS)

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outcome · POSTED

Arm A Compared to Arm B: Time to Next Treatment (TTNT), Assessed by Investigator

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outcome · POSTED

Arm A Compared to Arm B: Percentage of Participants With Overall Response (ORR), Assessed by IRC

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outcome · POSTED

Arm A Compared to Arm B: Percentage of Participants With Overall Response (ORR), Assessed by Investigator

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outcome · POSTED

Arm A Compared to Arm B: Duration of Response (DOR), Assessed by IRC

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outcome · POSTED

Arm A Compared to Arm B: Duration of Response (DOR), Assessed by Investigator

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outcome · POSTED

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

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outcome · POSTED

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

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outcome · POSTED

Arm A Compared to Arm B: Overall Survival, Assessed by Investigator

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: Inclusion Criteria: * 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) Exclusion Criteria: * 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 * 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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants received pirtobrutinib 200 milligrams (mg) orally once daily in continuous 28-day cycles until disease progression or unacceptable toxicity.
intervention Names
Drug: Pirtobrutinib
label
Arm A - Pirtobrutinib
type
EXPERIMENTAL
description
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).
intervention Names
Drug: Bendamustine
Drug: Rituximab
label
Arm B - Bendamustine Plus Rituximab
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
Arm A - Pirtobrutinib
description
Oral
name
Pirtobrutinib
other Names
LOXO-305
LY3527727
type
DRUG
arm Group Labels
Arm B - Bendamustine Plus Rituximab
description
IV
name
Bendamustine
other Names
Treanda
Treakisym
Ribomustin
Levact
type
DRUG
arm Group Labels
Arm B - Bendamustine Plus Rituximab
description
IV
name
Rituximab
other Names
Rituxan
MabThera
Truxima
Riabni
Ruxience
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

intervention 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 Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 282
type: ACTUAL

Registered outcome plans (not posted results)

other Outcomes

description
Overall survival (OS) is defined as the time from randomization until death from any cause. A descriptive analysis of OS was pre-specified based on the primary endpoint data cutoff.
measure
Arm A Compared to Arm B: Overall Survival, Assessed by Investigator
time Frame
From randomization until death from any cause (up to 41 months)

primary Outcomes

description
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.
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)

secondary Outcomes

description
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.
measure
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)
description
Assessments of effectiveness include OS, assessed by investigator
measure
To Evaluate the Effectiveness of Arm A Compared to Arm B: Overall Survival (OS)
time Frame
Up to approximately 5 years
description
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.
measure
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)
description
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.
measure
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)
description
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.
measure
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)
description
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.
measure
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)
description
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.
measure
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)
description
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.
measure
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
description
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.
measure
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

Full study description

brief 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.

Source references

references

citation
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.
pmid
41749915
type
DERIVED
citation
Jurczak 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.
pmid
41363773
type
DERIVED