Pirtobrutinib vs Ibrutinib for Chronic Lymphocytic Leukemia

(BRUIN-CLL-314 Trial)

Recruiting at 311 trial locations

Overseen By Physicians interested in becoming principal investigators please contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Loxo Oncology, Inc.

Must not be taking: Warfarin, Vitamin K antagonists

Disqualifiers: Richter's transformation, CNS involvement, cardiovascular disease, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 3 years and 5 months

662 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two treatments, pirtobrutinib (Jaypirca) and ibrutinib (Imbruvica), to determine which is more effective and safer for individuals with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). It compares these medications in patients who have received prior treatment and those who have not. A portion of the trial focuses on individuals with a specific genetic change, known as a 17p deletion. People with confirmed CLL or SLL who require treatment and can identify genetic changes might be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, providing patients an opportunity to contribute to potentially groundbreaking treatment advancements.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are on certain medications like warfarin, strong CYP3A inhibitors, or if you are using more than 20 mg of prednisone daily.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that pirtobrutinib is usually well-tolerated by people with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The most common side effects include infections, bleeding, and low levels of white blood cells, which are often manageable.

Studies have detailed the safety of ibrutinib. Serious side effects can include low white blood cell counts, low platelet counts, and pneumonia. These are known and monitored during treatment.

Both treatments have undergone thorough study. While some risks exist, they are generally considered safe for many patients. Always consult your healthcare provider about the potential risks and benefits before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for CLL?

Researchers are excited about pirtobrutinib for chronic lymphocytic leukemia (CLL) because it offers a fresh approach to treatment. Unlike standard options like ibrutinib, which targets the Bruton's tyrosine kinase (BTK) enzyme directly, pirtobrutinib is a next-generation BTK inhibitor designed to bind differently, potentially overcoming resistance that some patients develop with current treatments. This unique mechanism could mean better effectiveness and fewer side effects for patients who have had limited success with existing therapies.

What evidence suggests that this trial's treatments could be effective for chronic lymphocytic leukemia?

This trial will compare the effectiveness of pirtobrutinib and ibrutinib for treating chronic lymphocytic leukemia (CLL). Studies have shown that pirtobrutinib, which participants in this trial may receive, helps patients achieve longer progression-free survival (PFS) and has a 62% overall response rate. This indicates that many patients experience their cancer shrinking or remaining stable. Meanwhile, ibrutinib, another treatment option in this trial, has also proven effective, with many patients responding well. In real-world settings, ibrutinib has demonstrated an overall survival rate of 89% at 30 months. Both treatments are well-supported by research, but pirtobrutinib shows promise with its strong PFS and response rates. ^{2 6 7 8 9}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for people with CLL/SLL who may need treatment. They should have a certain level of platelets, hemoglobin, and neutrophils; adequate kidney function; and be in fair to good physical condition (ECOG 0-2). It's not for those with uncontrolled autoimmune issues, history of certain lymphomas or leukemia transformations, significant other diseases, active infections like hepatitis B/C or HIV, ongoing inflammatory bowel disease, prior BTK inhibitor use, on strong blood thinners or immune-suppressing drugs.

Inclusion Criteria

My platelet count is at least 50, or 30 if my bone marrow is affected.

My white blood cell count is within the required range.

I have been diagnosed with CLL/SLL and need treatment.

Exclusion Criteria

I am not using any experimental drugs or cancer treatments, except for hormone therapy.

I do not have any ongoing serious infections.

I have a condition that affects how my body absorbs medicine taken by mouth.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either pirtobrutinib (LOXO-305) or ibrutinib orally to compare efficacy and safety

3 years and 5 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Long-term follow-up

Participants are monitored for overall survival and other long-term outcomes

6 years

What Are the Treatments Tested in This Trial?

Interventions

• Ibrutinib
• Pirtobrutinib

Trial Overview The study compares Pirtobrutinib (LOXO-305) against Ibrutinib in treating CLL/SLL. Participants will either receive the new drug Pirtobrutinib or the established drug Ibrutinib to see which one works better and is safer. The trial could involve participants for up to six years.

How Is the Trial Designed?

Group I: Pirtobrutinib Part 2 Experimental Treatment 1 Intervention

Participants will receive pirtobrutinib orally.

Group II: Pirtobrutinib Part 1 Experimental Treatment 1 Intervention

Participants will receive pirtobrutinib orally.

Group III: Ibrutinib Active Control 1 Intervention

Participants will receive ibrutinib orally.

Ibrutinib is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in United States as Imbruvica for:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma
• Graft-versus-host disease

Approved in Canada as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia
• Marginal zone lymphoma

Approved in Japan as Imbruvica for:

• Chronic lymphocytic leukemia
• Mantle cell lymphoma
• Waldenström's macroglobulinemia

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

Published Research Related to This Trial

Ibrutinib is a first-in-class oral Bruton's tyrosine kinase inhibitor that effectively blocks B-cell signaling, leading to reduced proliferation and increased cell death in B cell malignancies, including chronic lymphocytic leukaemia (CLL) and mantle cell lymphoma (MCL).

It has received FDA approval for treating MCL in previously treated patients based on phase Ib/II study results and is currently undergoing further phase III trials for CLL, diffuse large B cell lymphoma (DLBCL), and other B cell cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: first global approval. Cameron, F., Sanford, M.[2022]

Ibrutinib is a targeted therapy specifically designed for treating chronic lymphocytic leukemia (CLL), which is a type of cancer that affects the blood and bone marrow.

This novel treatment works by inhibiting Bruton's tyrosine kinase (BTK), a key enzyme that helps cancer cells survive and proliferate, leading to improved patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib (imbruvica): a novel targeted therapy for chronic lymphocytic leukemia. Parmar, S., Patel, K., Pinilla-Ibarz, J.[2021]

Ibrutinib has shown high effectiveness as a first-line treatment for chronic lymphocytic leukemia in real-world settings, with 12-month overall survival rates between 95% and 96% and progression-free survival rates ranging from 89% to 93% across various studies involving 112 to 2033 patients.

The treatment demonstrated a strong response rate, with 71% to 90% of patients responding positively, and a significant majority (91% at 12 months and 87% at 24 months) did not require new treatment, indicating its sustained efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Literature Review of Real-World Effectiveness Results Data for First-Line Ibrutinib in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma. Lee, P., Kistler, KD., Douyon, L., et al.[2023]

In a phase 3 trial involving 652 patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), zanubrutinib demonstrated superior progression-free survival compared to ibrutinib, with a hazard ratio of 0.65, indicating a significant reduction in the risk of disease progression or death.

Zanubrutinib also had a better safety profile than ibrutinib, resulting in fewer adverse events that led to treatment discontinuation, particularly fewer cardiac events, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Zanubrutinib or Ibrutinib in Relapsed or Refractory Chronic Lymphocytic Leukemia. Brown, JR., Eichhorst, B., Hillmen, P., et al.[2023]

Ibrutinib is an effective treatment for chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL), showing better outcomes than traditional therapies like chlorambucil and ofatumumab in phase III trials involving elderly and previously-treated patients.

The drug has a good safety profile, although it can cause some adverse effects like bleeding and atrial fibrillation; it is recommended in treatment guidelines for patients with high-risk disease, including those with specific genetic mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ibrutinib: A Review in Chronic Lymphocytic Leukaemia. Deeks, ED.[2021]

Citations

1. ashpublications.org ashpublications.org/bloodadvances/article/9/15/3801/537228/Real-world-survival-outcomes-in-first-line

Real-world survival outcomes in first-line ibrutinib-treated ... The mean time from first observed diagnosis to 1L ibrutinib initiation was 38.0 (SD, 45.3) months among patients with high-risk CLL/SLL and 68.3 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11971162/

Final results on effectiveness and safety of Ibrutinib in patients ... 3). By 60 months, 96.8% of the retrospective patients had a response to ibrutinib treatment: 40.7% had a complete response and 56.1% a partial ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12311590/

Real-world survival outcomes in first-line ibrutinib-treated ... Real-world studies have also confirmed the benefit of 1L ibrutinib treatment; specifically, real-world OS (rwOS) rates were reported to be 89% at 30 months ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/10428194.2024.2402814

Real-world outcomes following ibrutinib dose reduction in ... Systematic literature review of real-world effectiveness results data for first-line ibrutinib in chronic lymphocytic leukemia and small lymphocytic lymphoma.

5. hematologyadvisor.com hematologyadvisor.com/news/pirtobrutinib-improves-pfs-in-treatment-naive-cll-sll-patients/

Pirtobrutinib Improves PFS in Treatment-Naïve CLL/SLL ... Findings showed patients treated with pirtobrutinib had a statistically significant and clinically meaningful improvement in PFS compared with ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40413564/

Real-World Safety Profile of Ibrutinib in Chronic ... The overall response rate was 82.2%, with 42.2% achieving complete remission. Multivariate analysis identified age and comorbidities as ...

7. nature.com nature.com/articles/s41408-022-00721-6

Clinical outcomes in patients with chronic lymphocytic ... The median OS of the entire cohort after progression on ibrutinib was 25.5 months (95% CI 17.7-31.0). Not unexpectedly, the OS was significantly ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S2950328024000645

Real-world safety profile of therapy with ibrutinib or ... Detailed safety profile of acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia in the ELEVATE-RR trial

9. imbruvicahcp.com imbruvicahcp.com/cll/efficacy/resonate-2/long-term-data

RESONATE-2 - Long-Term 8-Year Data - Imbruvica The most common grade ≥3 adverse reactions (≥5%) in adult patients with B-cell malignancies were neutropenia (21%)*, thrombocytopenia (14%)*, pneumonia (8%), ...