A Study of Pirtobrutinib (LOXO-305) Versus Ibrutinib in Participants With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) (BRUIN-CLL-314)
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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.
Percentage of Participants Achieving Complete Response (CR), Complete Remission with Incomplete Hematologic Recovery (Cri), Nodular Partial Remission (nPR) or Partial Response (PR): Overall Response Rate (ORR) [ Time Frame: Baseline to best overall response at or before the initiation of subsequent anti-cancer therapy (if any) (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 :
Event-Free Survival (EFS) [ Time Frame: Randomization to first occurrence of treatment discontinuation due to adverse event/toxicity, treatment-emergent atrial fibrillation or atrial flutter of any grade, progressive disease (PD) or death (approximately 4 years) ]
EFS by IRC per iwCLL 2018 criteria
Progression-Free Survival (PFS) [ Time Frame: Randomization to PD (per iwCLL 2018 criteria) or death from any cause (approximately 5 years 8 months) ]
PFS by IRC per iwCLL 2018 criteria
Duration of Response (DOR) [ Time Frame: Time from the date of the first documented response of CR, CRi, nPR or PR to the earlier of documentation of definitive PD (per iwCLL 2018 criteria) or death from any cause (approximately 2 years) ]
Overall Survival (OS) [ Time Frame: Randomization to death from any cause (approximately 6 years) ]
Time to Next Treatment (TTNT) [ Time Frame: Randomization to initiation of the next systemic anticancer therapy for CLL/SLL or death from any cause, whichever occurs first (approximately 6 years) ]
Time to Worsening (TTW) of CLL/SLL Related Symptoms [ Time Frame: Randomization to time to worsening symptoms (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.
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Ages Eligible for Study:
18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:
Accepts Healthy Volunteers:
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) or ≥30 x 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis,
Hemoglobin ≥8 grams/deciliter (g/dL) or ≥6 g/dL in participants with documented bone marrow involvement considered to impair hematopoiesis
Absolute neutrophil count ≥0.75 x 10⁹/L or ≥0.50 × 10⁹/L in participants with documented bone marrow involvement considered to impair hematopoiesis
Kidney function: Estimated creatinine clearance ≥30 milliliters per minute (mL/min)
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
Significant cardiovascular disease including ejection fraction < 40% and any grade ongoing atrial fibrillation or atrial flutter
Hepatitis B or hepatitis C testing indicating active/ongoing infection, based on Screening laboratory tests
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
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.
A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
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Studies a U.S. FDA-regulated Drug Product:
Studies a U.S. FDA-regulated Device Product:
Keywords provided by Eli Lilly and Company ( Loxo Oncology, Inc. ):