Intermittent Duvelisib for Chronic Lymphocytic Leukemia

Recruiting at 2 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inhibitors, PI3K inhibitors

Disqualifiers: HIV, Hepatitis B/C, Chronic liver disease, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well duvelisib on an intermittent (irregular) dosing schedule works in treating patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Duvelisib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving duvelisib on an intermittent schedule may result in similar effectiveness with less amount of severe side effects.

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 use certain cancer therapies, strong CYP3A4 inhibitors or inducers, or chronic corticosteroids above a certain dose before starting the trial.

What data supports the effectiveness of the drug Duvelisib for treating chronic lymphocytic leukemia?

Duvelisib has been shown to be effective in treating chronic lymphocytic leukemia (CLL) as it was approved by the FDA for patients with relapsed or refractory CLL after at least two prior therapies. In a large Phase III study, it demonstrated better progression-free survival and overall response rates compared to another treatment, ofatumumab. ^{1 2 3 4 5}

What safety data exists for Duvelisib in humans?

Duvelisib has been studied in various clinical trials for different types of blood cancers, showing that it can cause side effects like low white blood cell counts (neutropenia), low platelet counts (thrombocytopenia), and liver enzyme increases. In some studies, severe side effects were common, but careful management and dose adjustments helped patients continue treatment. Overall, Duvelisib was generally well tolerated in these trials. ^{1 2 3 6 7}

What makes the drug duvelisib unique for treating chronic lymphocytic leukemia?

Duvelisib is unique because it is an oral medication that targets two specific enzymes (PI3K-δ and PI3K-γ) involved in cancer cell growth, making it effective for patients with chronic lymphocytic leukemia who have not responded to other treatments. Its dual action and oral administration set it apart from other therapies. ^{1 2 3 4 8}

Research Team

Alexey V Danilov

Principal Investigator

City of Hope Comprehensive Cancer Center

Eligibility Criteria

This trial is for adults with chronic lymphocytic leukemia or small lymphocytic lymphoma who've had at least one prior treatment and need more because their disease has progressed or hasn't improved. They must be able to take pills, have decent organ function, and not be pregnant or breastfeeding. People can't join if they've recently used certain drugs, have uncontrolled other diseases, are on high-dose steroids, or have a history of severe heart problems.

Inclusion Criteria

Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) less than 2.5 x institutional ULN (prior to starting study drug)

My blood platelet count is at least 30,000 and my neutrophil count is at least 500, without recent transfusions.

My kidneys are functioning well enough for treatment.

Exclusion Criteria

I haven't taken specific cancer treatments like antibodies, radio-toxins, or targeted therapy recently.

I haven't had a stroke, heart attack, severe chest pain, or serious heart rhythm problems needing treatment or a pacemaker in the last 6 months.

I have a history of HIV or active hepatitis B or C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive duvelisib orally twice daily on days 1-28. Cycles repeat every 28 days for 12 weeks in the absence of disease progression or unacceptable toxicity.

12 weeks

Maintenance

Patients receive duvelisib orally twice daily on days 1-2, 8-9, 15-16, and 22-23. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Variable, based on disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Every 3 months

Treatment Details

Interventions

• Duvelisib

Trial Overview The trial is testing the effectiveness of Duvelisib given intermittently in patients with specific types of blood cancer. Researchers want to see if taking this drug irregularly might control the cancer while causing fewer serious side effects compared to regular dosing schedules.

Participant Groups

Group I: Treatment (duvelisib) Experimental Treatment 1 Intervention

INDUCTION: Patients receive duvelisib PO BID on days 1-28. Cycles repeat every 28 days for 12 weeks in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive duvelisib PO BID on days 1-2, 8-9, 15-16, and 22-23. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Duvelisib is already approved in United States for the following indications:

Approved in United States as Copiktra for:

• Relapsed or refractory chronic lymphocytic leukemia (CLL)
• Relapsed or refractory small lymphocytic lymphoma (SLL)

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

Duvelisib is an oral small-molecule inhibitor of phosphatidylinositol-3 kinase that received its first global approval in the USA in September 2018 for treating adult patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) after at least two prior therapies.

It also received accelerated approval for treating adult patients with relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies, indicating its efficacy in multiple hematological malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duvelisib: First Global Approval. Blair, HA.[2019]

Duvelisib is a dual inhibitor of PI3Kδ and PI3Kγ, approved by the FDA in 2018 for treating adult patients with relapsed or refractory chronic lymphocytic leukaemia (CLL) and small lymphocytic lymphoma (SLL) after at least two prior therapies.

It has also received accelerated approval for relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies, highlighting its efficacy in difficult-to-treat blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duvelisib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Phosphoinositide 3-Kinases. Rodrigues, DA., Sagrillo, FS., Fraga, CAM.[2020]

Duvelisib, an oral dual inhibitor of PI3K-δ and -γ, showed promising efficacy in treating advanced hematologic malignancies, with an overall response rate of 56.4% in relapsed/refractory chronic lymphocytic leukemia (CLL) patients and 83.3% in treatment-naïve CLL patients.

The most common side effects included diarrhea (78% in treatment-naïve and 47% in relapsed/refractory patients) and transaminase elevations, indicating that while duvelisib is effective, it also has notable safety considerations that need monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duvelisib, an oral dual PI3K-δ,γ inhibitor, shows clinical and pharmacodynamic activity in chronic lymphocytic leukemia and small lymphocytic lymphoma in a phase 1 study. O'Brien, S., Patel, M., Kahl, BS., et al.[2023]

Duvelisib, a dual inhibitor of PI3Kδ and PI3Kγ, has been approved by the FDA for treating patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma after at least two prior therapies.

The drug also received accelerated approval for patients with relapsed or refractory follicular lymphoma, indicating its potential effectiveness in these difficult-to-treat cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duvelisib Approved for Leukemia, Lymphoma. [2019]

Duvelisib, a dual inhibitor of PI3K-δ and -γ, was well tolerated in a phase I study involving 7 Japanese patients with relapsed or refractory lymphoma, with no dose-limiting toxicities reported.

The treatment showed promising preliminary efficacy, with an overall response rate of 71.4%, including one complete response and several partial responses among the patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of duvelisib in Japanese patients with relapsed or refractory lymphoma. Izutsu, K., Kato, K., Kiyoi, H., et al.[2022]

Duvelisib, an oral dual inhibitor targeting PI3K-δ and PI3K-γ, was found to have a maximum tolerated dose of 75 mg twice daily in a phase 1 study involving 210 patients with advanced hematologic malignancies, showing promising efficacy across various cancer types.

The treatment resulted in significant clinical responses, with overall response rates of 58% in indolent non-Hodgkin lymphoma and 56% in relapsed/refractory chronic lymphocytic leukemia, although severe adverse events were reported in 84% of patients, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duvelisib, a novel oral dual inhibitor of PI3K-δ,γ, is clinically active in advanced hematologic malignancies. Flinn, IW., O'Brien, S., Kahl, B., et al.[2023]

Duvelisib, a dual inhibitor of PI3Kδ and PI3Kγ, was tested on 30 pediatric acute lymphoblastic leukemia (ALL) patient-derived xenografts (PDXs) and was found to be well-tolerated, but showed limited efficacy with only one objective response despite reducing leukemia cells in some cases.

The study revealed no clear relationship between the drug's effectiveness and the expression or mutation status of PI3Kδ or PI3Kγ, indicating that duvelisib's action may not be dependent on these factors in the context of ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo activity of the dual PI3Kδ and PI3Kγ inhibitor duvelisib against pediatric acute lymphoblastic leukemia xenografts. Randall, J., Evans, K., Watts, B., et al.[2023]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Duvelisib: First Global Approval. [2019]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Duvelisib: A 2018 Novel FDA-Approved Small Molecule Inhibiting Phosphoinositide 3-Kinases. [2020]

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

Duvelisib: a new phosphoinositide-3-kinase inhibitor in chronic lymphocytic leukemia. [2021]

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

Duvelisib, an oral dual PI3K-δ,γ inhibitor, shows clinical and pharmacodynamic activity in chronic lymphocytic leukemia and small lymphocytic lymphoma in a phase 1 study. [2023]

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

Duvelisib Approved for Leukemia, Lymphoma. [2019]

6. Japan pubmed.ncbi.nlm.nih.gov

Phase I study of duvelisib in Japanese patients with relapsed or refractory lymphoma. [2022]

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

Duvelisib, a novel oral dual inhibitor of PI3K-δ,γ, is clinically active in advanced hematologic malignancies. [2023]

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

In vivo activity of the dual PI3Kδ and PI3Kγ inhibitor duvelisib against pediatric acute lymphoblastic leukemia xenografts. [2023]