PCI-32765 for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Must not be taking: Corticosteroids, Warfarin, Strong inhibitors

Disqualifiers: Transformed CLL, Hepatitis B, HIV, others

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

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

Compensation: Varies

Number of Visits: 1

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called PCI-32765, a potential drug for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The goal is to determine if this drug can benefit older individuals and those with a specific genetic issue, the 17p deletion, who typically do not respond well to standard treatments. Participants will take the medicine daily for a series of cycles, and doctors will monitor health improvements with regular tests. This trial may suit those over 65 with CLL/SLL or anyone with CLL/SLL who has the 17p deletion and experiences symptoms like ongoing fevers or severe fatigue. As a Phase 2 trial, research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot participate if you need certain treatments like strong CYP3A4/5 and CYP2D6 inhibitors, or if you require anticoagulation with warfarin. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that PCI-32765 is likely to be safe for humans?

Previous studies have shown that PCI-32765, also known as ibrutinib, is safe for people with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Research indicates that even patients with other health issues or high-risk genetic traits, like the 17p deletion, tolerate this treatment well. This is especially important for older patients who may not tolerate standard chemotherapy.

The FDA has approved ibrutinib for treating CLL/SLL, confirming its safety for these conditions. Most side effects can be managed, and patients generally respond well to the drug. Studies have demonstrated its effectiveness and safety for long-term use in similar patient groups. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Chronic Lymphocytic Leukemia (CLL), such as chemotherapy and monoclonal antibodies, PCI-32765 offers a novel approach by specifically targeting Bruton's tyrosine kinase (BTK). This mechanism blocks the signals that promote cancer cell survival, potentially leading to more effective results with fewer side effects. Researchers are particularly excited because PCI-32765 can be especially beneficial for patients with specific conditions, like those over 65 or with the 17p deletion, who often have limited options with existing therapies.

What evidence suggests that PCI-32765 might be an effective treatment for CLL/SLL?

Research has shown that PCI-32765, also known as Ibrutinib, effectively treats chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In one study, 96.8% of patients responded to Ibrutinib, with 40.7% achieving a complete response and 56.1% a partial response. Importantly, patients treated with Ibrutinib have demonstrated good survival rates, even those with challenging genetic conditions like the 17p deletion. This trial will evaluate Ibrutinib in different participant groups, including older patients over 65 and those with the 17p deletion. Another review confirmed its effectiveness as a first-choice treatment for CLL in real-world situations. Overall, Ibrutinib shows promise, especially for older patients and those with genetic challenges. ^{6 7 8 9 10}

Who Is on the Research Team?

Andy Itsara, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Are You a Good Fit for This Trial?

This trial is for adults with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma. It's specifically for those over 65, or at least 18 with a genetic abnormality called 17p deletion. Participants must be able to swallow capsules and agree to use contraception if they can have children.

Inclusion Criteria

Active disease as defined by weight loss greater than or equal to 10% within the previous 6 months, extreme fatigue, fevers of greater than 100.5 degrees F for greater than or equal to 2 weeks without evidence of infection, night sweats for more than one month without evidence of infection, evidence of progressive marrow failure, massive or progressive splenomegaly, massive nodes or clusters or progressive lymphadenopathy, progressive lymphocytosis, compensated autoimmune hemolysis, Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2, ANC greater than 500/microL, platelets greater than 30,000/microL, agreement to use contraception during the study and for 90 days after the last dose of study drug if sexually active and able to bear children, willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty, ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations)

I am 65 or older and need treatment.

I am over 18 and have cancer with specific genetic changes.

Exclusion Criteria

Known hypersensitivity to any component of PCI-32765

I need to take warfarin for blood thinning.

I have never taken PCI 32765 or any BTK inhibitors.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants take PCI-32765 capsules every day for 28 days per cycle, monitored with frequent blood tests and clinic visits

24 weeks

Frequent visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Regular follow-up exams

What Are the Treatments Tested in This Trial?

Interventions

• PCI-32765

Trial Overview

The trial tests PCI-32765, a new drug for treating CLL/SLL in older patients and those with the 17p deletion who often don't do well on standard treatments. Patients take daily capsules for six cycles and may continue if beneficial without severe side effects.

How Is the Trial Designed?

Group I: Elderly greater than 65 Experimental Treatment 1 Intervention

Group II: 17p Deletioin Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

National Heart, Lung, and Blood Institute (NHLBI)

Lead Sponsor

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

The review focused on both approved and emerging therapies for chronic lymphocytic leukemia (CLL), highlighting their mechanisms of action and efficacy in treating the disease.

It also addressed the management of adverse events related to these therapies, emphasizing the importance of safety in treatment strategies for CLL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving Outcomes for Patients With Chronic Lymphocytic Leukemia. Shadman, M., Goodrich, A.[2021]

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]

Citations

1.

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 ...

2.

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 ...

Among patients with CLL/SLL treated with 1L ibrutinib, similar rwOS was observed for those with or without high-risk cytogenetic features.

3.

pubmed.ncbi.nlm.nih.gov

pubmed.ncbi.nlm.nih.gov/36534239/

Systematic Literature Review of Real-World Effectiveness ...

This systematic literature review confirms the benefit of ibrutinib as a first-line treatment in patients with chronic lymphocytic leukemia in real-world ...

4.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01589302

NCT01589302 | PCI-32765 (Ibrutinib) in Treating Patients ...

This study will involve treating patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or B-cell prolymphocytic leukemia (B-PLL) ...

5.

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.

6.

pubmed.ncbi.nlm.nih.gov

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

Real-World Safety Profile of Ibrutinib in Chronic ...

Ibrutinib remains an effective treatment for lymphocytic leukemia, even in patients with comorbidities and high-risk genetic characteristics.

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01105247

Safety of PCI-32765 in Chronic Lymphocytic Leukemia

The purpose of this study is to establish the safety and efficacy of orally administered PCI-32765 in patients with chronic lymphocytic leukemia/small ...

8.

ahdbonline.com

ahdbonline.com/articles/updated-efficacy-and-safety-from-the-phase-3-resonate-2-study-ibrutinib-as-first-line-treatment-option-in-patients-65-years-and-older-with-chronic-lymphocytic-leukemia-small-lymphocytic-leukemia

Updated Safety and Efficacy Data for Ibrutinib as First-Line ...

Ibrutinib is the first FDA-approved once-daily inhibitor of Bruton's tyrosine kinase indicated for the treatment of patients with CLL/SLL, thereby allowing this ...

9.

ashpublications.org

ashpublications.org/bloodneoplasia/article/2/1/100064/534858/Real-world-safety-profile-of-therapy-with

Real-world safety profile of therapy with ibrutinib or ...

The ELEVATE-RR trial compared treatment with ibrutinib vs acalabrutinib in previously treated CLL, showing similar progression-free survival with both agents.

10.

sciencedirect.com

sciencedirect.com/science/article/pii/S2152265018302659

Safety Analysis of Four Randomized Controlled Studies ...

Multiple studies have demonstrated the efficacy and safety of ibrutinib for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and mantle cell ...