PCI-32765 for Chronic Lymphocytic Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

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

86 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: - Chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) are types of blood or lymph node cancers that mostly affect the elderly. CLL/SLL both create abnormal white blood cells that hurt the immune system and make it more difficult to fight infections. These cancers are usually diagnosed after age 50; more than half of the people with CLL/SLL are over age 70. Elderly people often do not respond well to standard chemotherapy for CLL/SLL. They may have other health problems that make chemotherapy difficult. In addition, individuals who have a genetic abnormality called 17p deletion also do not respond well to standard treatments for CLL/SLL. Researchers want to test a new cancer treatment drug, PCI-32765, to see if it can treat CLL/SLL in these hard-to-treat groups. Objectives: - To see if PCI-32765 is a safe and effective treatment for CLL/SLL in older people and people with 17p deletion. Eligibility: * Individuals over 65 years of age who have CLL/SLL. * Individuals at least 18 years of age who have CLL/SLL and 17p deletion. Design: * Participants will be screened with a medical history, physical exam, and imaging studies. Blood and urine samples will be taken. Optional bone marrow and lymph node biopsies may also be taken. * Participants will take PCI-32765 capsules every day for 28 days (one cycle of treatment). Treatment will be monitored with frequent blood tests and clinic visits. * PCI-32765 will be given for six cycles of treatment. Those who benefit from the drug will continue to take it as long as there are no side effects and the disease does not progress. Those who do not benefit will stop treatment and have regular followup exams.

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.

What data supports the effectiveness of the drug PCI-32765 for chronic lymphocytic leukemia?

The research mentions that new biological agents like ibrutinib, which is similar to PCI-32765, have been effective in treating chronic lymphocytic leukemia. This suggests that PCI-32765 may also be effective, as it is a similar type of drug. ^{1 2 3 4 5}

What safety data exists for PCI-32765 (ibrutinib) in humans?

Ibrutinib, also known as PCI-32765, is generally considered safe but can have side effects like diarrhea, fatigue, joint pain, infections, low blood cell counts, bleeding, and heart-related issues such as irregular heartbeat and high blood pressure. ^{4 6 7 8 9}

How is the drug PCI-32765 unique in treating chronic lymphocytic leukemia?

PCI-32765, also known as ibrutinib, is unique because it targets the B-cell receptor pathway, which is particularly effective for patients with chronic lymphocytic leukemia who have 17p deletions, a group that typically responds poorly to traditional chemoimmunotherapy. ^{1 3 4 6 10}

Research Team

Andy Itsara, M.D.

Principal Investigator

National Heart, Lung, and Blood Institute (NHLBI)

Eligibility Criteria

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 have never taken PCI 32765 or any BTK inhibitors.

I need to take warfarin for blood thinning.

Timeline

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

Treatment Details

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.

Participant Groups

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+

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]

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]

References

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

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2. Austria pubmed.ncbi.nlm.nih.gov

[Chronic lymphatic leukemia]. [2007]

3. England pubmed.ncbi.nlm.nih.gov

Chronic Lymphocytic Leukemia: Diagnosis and Treatment. [2019]

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

A clinical update on chronic lymphocytic leukemia. II. Critical analysis of current chemotherapeutic modalities. [2019]

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

Baseline Characteristics Predicting Very Good Outcome of Allogeneic Hematopoietic Cell Transplantation in Young Patients With High Cytogenetic Risk Chronic Lymphocytic Leukemia - A Retrospective Analysis From the Chronic Malignancies Working Party of the EBMT. [2018]

6. 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]

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

Improving Outcomes for Patients With Chronic Lymphocytic Leukemia. [2021]

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

Thalidomide and lenalidomide as new therapeutics for the treatment of chronic lymphocytic leukemia. [2021]

9. Switzerland pubmed.ncbi.nlm.nih.gov

How I Manage Chronic Lymphocytic Leukemia. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Induction of graft-versus-leukemia effect in a patient with chronic lymphocytic leukemia. [2021]