LOXO-305 for Chronic Lymphocytic Leukemia

(BRUIN CLL-321 Trial)

Recruiting at 268 trial locations

Overseen By Seo-Hyun Kim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Loxo Oncology, Inc.

Must be taking: BTK inhibitors

Must not be taking: Warfarin, CYP3A4 inhibitors

Disqualifiers: Richter's transformation, CNS involvement, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 months

238 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a study for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have previously received treatment with at least a BTK inhibitor. The main purpose is to compare LOXO-305 to idelalisib plus rituximab or bendamustine plus rituximab. Participation could last up to four years, and possibly longer, if the disease does not progress.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you cannot participate if you are currently on strong CYP3A4 inhibitors or inducers, or if you require therapeutic anticoagulation with warfarin or another Vitamin K antagonist.

What evidence supports the effectiveness of the drug LOXO-305 for treating chronic lymphocytic leukemia?

Idelalisib, a component of the treatment, has shown excellent activity in chronic lymphocytic leukemia, especially in patients with certain genetic mutations. Additionally, Rituximab, when combined with standard chemotherapy, improves response rates and may prolong survival in patients with this condition. ^{1 2 3 4 5}

Research Team

Marisa Hill, MD

Principal Investigator

Loxo Oncology, Inc.

Eligibility Criteria

This trial is for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) who have had previous treatment including a BTK inhibitor. They should be in fairly good health, with specific blood counts and organ function levels meeting the study's criteria. People with certain heart diseases, active infections like hepatitis or HIV, recent live vaccinations, or known allergies to the drugs being tested cannot join.

Inclusion Criteria

I can perform daily activities with little to no assistance.

AST and ALT ≤ 3.0 x upper limit of normal (ULN)

Total bilirubin ≤ 1.5 x ULN

Exclusion Criteria

I have an active, uncontrolled immune system disorder affecting my blood cells.

I have a serious heart condition.

Known hypersensitivity, including anaphylaxis, to any component or excipient of LOXO-305. For patients planned to receive idelalisib, known hypersensitivity, including anaphylaxis, to any component or excipient of idelalisib. For patients planned to receive bendamustine, known hypersensitivity, including anaphylaxis, to any component or excipient of bendamustine

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either LOXO-305 or investigator's choice of idelalisib plus rituximab or bendamustine plus rituximab. Treatment continues until disease progression, discontinuation, or unacceptable toxicity.

Up to 36 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term if the disease does not progress

Long-term

Treatment Details

Interventions

• Bendamustine
• Idelalisib
• LOXO-305
• Rituximab

Trial Overview The study compares LOXO-305 against two other treatments: Idelalisib plus Rituximab or Bendamustine plus Rituximab. Patients will receive one of these treatments based on random assignment and could participate for up to four years if their disease doesn't worsen.

Participant Groups

Group I: Arm A - Pirtobrutinib Experimental Treatment 1 Intervention

Participants received 200 milligrams (mg) of pirtobrutinib administered orally once daily (QD) on Days 1 through 28 of a 28-day cycle. The treatment was continued until progressive disease, a discontinuation criterion, or unacceptable toxicity.

Group II: Arm B - Idelalisib plus Rituximab or Bendamustine plus Rituximab Active Control 3 Interventions

Participants received either 150 mg of idelalisib administered twice-daily (BID) orally on Days 1 through 28 of a 28-day cycle in combination with 375 milligram per square meter (mg/m\^2) of rituximab by intravenous (IV) infusion on day 1 of cycle 1, then 4 IV infusions of rituximab 500 mg/m\^2 every 2 weeks (Q2W) and 3 IV infusions of rituximab 500 mg/m\^2 every 4 weeks (Q4W) or 70 mg/m\^2 of bendamustine administered IV on day 1 and 2 of each 28-day cycle from cycles 1 to 6 in combination with 375 mg/m\^2 of rituximab IV on day 1 of cycle 1, then 500 mg/m\^2 of rituximab on day 1 of each 28-day cycle from cycles 2 to 6.

Who Is Running the Clinical Trial?

Loxo Oncology, Inc.

Lead Sponsor

Trials

72

Recruited

11,600+

Jacob Van Naarden

Loxo Oncology, Inc.

Chief Executive Officer since 2019

A.B. in Molecular Biology from Princeton University

Dr. Jennifer Low

Loxo Oncology, Inc.

Chief Medical Officer since 2014

MD and PhD from Georgetown University; Undergraduate degree from California Institute of Technology

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Findings from Research

Recent advancements in treatment options for chronic lymphocytic leukemia (CLL) include novel targeted therapies like obinutuzumab and ofatumomab, which are effective and well-tolerated, especially for elderly patients or those with other health issues.

Ibrutinib and idelalisib show excellent efficacy in CLL, particularly for patients with 17p deletions, while the newly FDA-approved venetoclax offers promising results for those with relapsed or refractory disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expanding the armamentarium for chronic lymphocytic leukemia: A review of novel agents in the management of chronic lymphocytic leukemia. Marini, BL., Samanas, L., Perissinotti, AJ.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Expanding the armamentarium for chronic lymphocytic leukemia: A review of novel agents in the management of chronic lymphocytic leukemia. [2021]

2. Poland pubmed.ncbi.nlm.nih.gov

Practical approach to management of chronic lymphocytic leukemia. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Monoclonal antibody therapy of chronic lymphocytic leukaemia. [2010]

4. England pubmed.ncbi.nlm.nih.gov

Chronic Lymphocytic Leukemia: Diagnosis and Treatment. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

State-of-the-art treatment of chronic lymphocytic leukemia. [2019]