Intermittent Duvelisib for Chronic Lymphocytic Leukemia

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of duvelisib when taken on an irregular schedule to treat chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL), both types of blood cancer. The goal is to determine if less frequent dosing of duvelisib remains effective while reducing severe side effects. Suitable participants have previously tried other treatments without success and experience symptoms such as extreme tiredness or unintentional weight loss. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that duvelisib is likely to be safe for humans?

Research has shown that duvelisib, the treatment under study, is generally safe for patients with chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). In earlier studies, more than 10% of patients experienced side effects unrelated to blood cells. Common side effects include serious infections, diarrhea or colon inflammation, and skin reactions.

One study found that duvelisib can help patients live longer without disease progression and improve their response to treatment compared to another drug, ofatumumab. However, the FDA has warned about a 15% higher risk of death with duvelisib, along with these severe side effects. Despite these risks, doctors can usually manage the side effects if they occur.

In summary, while risks exist, duvelisib has proven effective, and its side effects can be managed with medical supervision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for chronic lymphocytic leukemia, which often include chemotherapy and monoclonal antibodies, duvelisib offers a novel approach by inhibiting PI3K enzymes. This action specifically targets pathways crucial for cancer cell growth and survival, potentially leading to more effective disease management. Researchers are excited about duvelisib because it is taken orally, providing a more convenient option compared to intravenous therapies, and it may offer a favorable side effect profile, allowing intermittent dosing that could improve patient quality of life.

What evidence suggests that duvelisib might be an effective treatment for chronic lymphocytic leukemia?

Studies have shown that duvelisib can effectively treat chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL). Research indicates that duvelisib blocks certain enzymes that cancer cells need to grow, helping to stop the cancer from growing or spreading. In previous studies, patients treated with duvelisib showed promising results, suggesting it as a potential option for those needing more treatment choices. However, evidence also shows that duvelisib can cause serious side effects, such as infections and digestive problems. The current study aims to determine if taking duvelisib intermittently, as outlined in the trial's treatment arm, might reduce these side effects while maintaining effectiveness. ^{2 3 4 6 7}

Who Is on the Research Team?

Alexey V Danilov

Principal Investigator

City of Hope Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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, 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, 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11443371/

The phase III DUO trial of PI3K inhibitor duvelisib versus ... Results from DUO suggest that duvelisib monotherapy may offer an effective treatment for CLL/SLL patients in need of additional therapeutic options.

2. healthtree.org healthtree.org/cll/community/articles/duvelisib-risk-benefit-warning-cll

FDA Warns About Risk-Benefit Balance of Duvelisib for CLL Duvelisib was found to increase the risk of death by 15% and was associated with severe side effects, including serious infections, diarrhea/colitis, skin ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02049515

A Phase 3 Extension Study of Duvelisib and Ofatumumab ... A Phase 3 (extension) clinical trial to examine the efficacy of IPI-145 (duvelisib) monotherapy or ofatumumab monotherapy in participants with chronic ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/211155Orig1Orig2s000MultidisciplineR.pdf

211155Orig1s000 211155Orig2s000 - accessdata.fda.gov chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at ... The pivotal evidence of effectiveness comes from the efficacy ...

5. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1070660/full

Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in ... This systematic review and meta-analysis aimed to evaluate the safety and efficacy of duvelisib in treating different relapsed or refractory (RR) lymphoid ...

6. copiktrahcp.com copiktrahcp.com/cll-sll/safety/

Safety Profile - COPIKTRA® (duvelisib) - HCP Site COPIKTRA has an established safety profile for patients with CLL/SLL. Nonhematologic adverse reactions (ARs) occurring in ≥10% of patients receiving COPIKTRA.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04209621

Duvelisib for Ibrutinib-Resistant Chronic Lymphocytic ... Duvelisib monotherapy improved progression-free survival and overall response rate compared to ofatumumab and had a manageable safety profile in subjects with ...