BRUIN-CLL-314: A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL)

Loxo Oncology, Inc. (Industry)
Overall Status
Recruiting ID

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy and safety of pirtobruitinib (LOXO-305) to ibrutinib in participants with CLL/SLL. Participants may or may not have already had treatment for their cancer. Participation could last up to six years.

Study Design

Study Type:
Anticipated Enrollment :
650 participants
Intervention Model:
Parallel Assignment
None (Open Label)
Primary Purpose:
Official Title:
A Phase 3 Open-Label, Randomized Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Patients With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (BRUIN-CLL-314)
Actual Study Start Date :
Jul 22, 2022
Anticipated Primary Completion Date :
Mar 24, 2028
Anticipated Study Completion Date :
Mar 24, 2029

Arms and Interventions

Arm Intervention/Treatment
Experimental: Pirtobrutinib

Administered orally.

Drug: Pirtobrutinib
Administered orally.
Other Names:
  • LOXO-305
  • LY3527727
  • Experimental: Ibrutinib

    Administered orally.

    Drug: Ibrutinib
    Administered orally.

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants Achieving Complete Response (CR) or Partial Response (PR): Overall Response Rate (ORR) [Baseline to disease progression (up to approximately 3 years and 5 months)]

      ORR as assessed by independent review committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2018 criteria

    Secondary Outcome Measures

    1. Event-Free Survival (EFS) [Randomization until treatment discontinuation due to adverse event (AE)/toxicity, atrial fibrillation or atrial flutter of any grade, or progressive disease (PD) (by IRC per iwCLL 2018 criteria) or death (up to approximately 4 years)]


    2. Progression-Free Survival (PFS) [Randomization until PD (per iwCLL 2018 criteria) or death from any cause (up to approximately 5 years 8 months)]


    3. Time to worsening (TTW) of CLL/SLL related symptoms [Randomization to time to worsening symptoms (up to approximately 6 years)]

      Using symptom questions identified from the EORTC item library. The range of raw scores for these items could be from 0 to 52 with highest score being worse symptoms.

    Eligibility Criteria


    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    Accepts Healthy Volunteers:
    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 (≥)50 x 10⁹/liter (L), hemoglobin ≥8 grams/deciliter (g/dL), and absolute neutrophil count ≥0.75 x 10⁹/L

    • Kidney function: Estimated creatinine clearance ≥30 milliliters per minute (mL/min)

    Exclusion Criteria:
    • Known or suspected Richter's transformation to diffuse large B-cell lymphoma (DLBCL), prolymphocytic leukemia, or Hodgkin's lymphoma at any time preceding enrollment

    • Known or suspected central nervous system (CNS) involvement

    • A significant history of renal, neurologic, psychiatric, endocrine, metabolic or immunologic disease

    • 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, or fungal infection

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

    • Clinically significant active malabsorption syndrome or other condition likely to affect GI absorption of the oral-administered study treatments

    • Ongoing inflammatory bowel disease

    • Prior exposure to BTK inhibitor (covalent or noncovalent)

    • Concurrent use of investigational agent or anticancer therapy except hormonal therapy

    • Participants requiring therapeutic anticoagulation with warfarin or another Vitamin K antagonist

    • Use of ≥ 20 mg prednisone daily or equivalent dose of steroid at the time of first dose of study drug

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

    • Participants receiving chronic therapy with a strong cytochrome P450 (CYP)3A inhibitor (except posaconazole and voriconazole) which cannot be stopped within 3-5 half lives of the CYP3A inhibitor therapy prior to start of study drug treatment.

    • Participants with known hypersensitivity, including anaphylaxis, to any component or excipient of pirtobrutinib or ibrutinib

    Contacts and Locations


    Site City State Country Postal Code
    1 Innovative Clinical Research Institute Whittier California United States 90603

    Sponsors and Collaborators

    • Loxo Oncology, Inc.


    • Study Director: 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), Eli Lilly and Company

    Study Documents (Full-Text)

    None provided.

    More Information


    None provided.
    Responsible Party:
    Loxo Oncology, Inc. Identifier:
    Other Study ID Numbers:
    • 18281
    • J2N-OX-JZNU
    • LOXO-BTK-20030
    • 2021-003206-41
    First Posted:
    Feb 24, 2022
    Last Update Posted:
    Aug 10, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Plan to Share IPD:
    Studies a U.S. FDA-regulated Drug Product:
    Studies a U.S. FDA-regulated Device Product:
    Keywords provided by Loxo Oncology, Inc.
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 10, 2022