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

Sponsor

Loxo Oncology, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05254743

Collaborator

(none)

650

Enrollment

Location

Arms

80.1

Anticipated Duration (Months)

8.1

Patients Per Site Per Month

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Lymphocytic Leukemia Leukemia, Lymphocytic Leukemia, B-cell Small Lymphocytic Lymphoma	Drug: Pirtobrutinib Drug: Ibrutinib	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

650 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

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

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

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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

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

Locations

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

Sponsors and Collaborators

Loxo Oncology, Inc.

Investigators

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