Duvelisib Maintenance for T-Cell Lymphoma

Overseen By Amanda Cashen, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Immunosuppressants, Systemic steroids, CYP3A inducers

Disqualifiers: Lung disease, Liver disease, Infections, 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

Duration: 12 months

17 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators hypothesize that duvelisib maintenance after autologous stem cell transplant in patients with T-cell lymphomas will be safe and well tolerated, and will improve progression free survival.

Will I have to stop taking my current medications?

The trial does not specify if you must stop all current medications, but you cannot take certain medications that strongly affect liver enzymes (CYP3A) within 2 weeks before starting the study. Also, ongoing treatment with high-dose steroids or certain immunosuppressants is not allowed.

What data supports the effectiveness of the drug Duvelisib for T-Cell Lymphoma?

Research shows that Duvelisib, a drug that blocks certain proteins involved in cancer cell growth, has shown promising results in treating T-Cell Lymphoma. In a study, 50% of patients with peripheral T-Cell Lymphoma and 32% with cutaneous T-Cell Lymphoma responded to the treatment, with some achieving complete responses. ^{1 2 3 4 5}

What is known about the safety of Duvelisib in humans?

Duvelisib has been studied for safety in patients with various types of lymphoma. Common side effects include low levels of white blood cells (neutropenia), low platelet counts (thrombocytopenia), and liver function changes. It was generally well tolerated in clinical trials, but monitoring for these side effects is important. ^{1 4 6 7 8}

How is the drug duvelisib unique for treating T-cell lymphoma?

Duvelisib is unique because it is an oral drug that targets two specific enzymes (PI3K-δ and PI3K-γ) involved in cancer cell growth and survival, making it different from other treatments that may not target these pathways. It has shown promise in treating various blood cancers, including T-cell lymphoma, by inhibiting cancer cell proliferation. ^{1 2 3 8 9}

Research Team

Amanda Cashen, MD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

Adults with certain types of T-cell lymphoma eligible for or have had a stem cell transplant can join. They must be generally healthy, not pregnant, and agree to use contraception. Excluded are those with severe lung disease, recent heart issues, drug allergies similar to duvelisib's components, active infections or other cancers needing treatment.

Inclusion Criteria

I am using effective birth control and have a negative pregnancy test.

I have been diagnosed with a type of T cell non-Hodgkin lymphoma.

Participants or a participant's legally authorized representative must be able to understand and willing to sign an IRB approved written informed consent document

Exclusion Criteria

I cannot receive preventive treatments for certain infections.

I have no active cancer except for certain skin, cervical, bladder, or prostate cancers that don't need treatment.

I do not have active hepatitis B or C.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Duvelisib maintenance at 25 mg PO BID after count recovery for one year post-transplant

12 months

Regular visits for PET/CT scans every 3 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Duvelisib

Trial Overview The trial is testing if taking the drug duvelisib after a stem cell transplant is safe and helps patients with T-cell lymphomas live longer without their cancer getting worse. Participants will receive regular doses of duvelisib and undergo blood tests to monitor effects.

Participant Groups

Group I: Duvelisib Maintenance Experimental Treatment 2 Interventions

* Duvelisib maintenance at 25 mg PO BID after count recovery (approximately 30 days after transplant) for one year. If the patient is in a complete remission at day +100, with no evidence of disease on PET/CT, then the dosing schedule of duvelisib may be changed to 25 mg BID for 14 days, then 14 days off in 28 day cycles (at the treating physician's discretion). If the patient has residual disease, duvelisib will continue at 25 mg BID until they have a negative PET CT. PET CTs will be completed every 3 months for patients with residual disease. Duvelisib maintenance will be continued for one year post-transplant. * Starting on 06/10/2021, all new participants will be enrolled to take 25 mg BID of duvelisib on days 1-14 of a 28 day cycle.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

SecuraBio

Industry Sponsor

Trials

29

Recruited

2,400+

Findings from Research

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 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]

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 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

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

2. England pubmed.ncbi.nlm.nih.gov

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

3. 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]

4. 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]

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

Activity of the PI3K-δ,γ inhibitor duvelisib in a phase 1 trial and preclinical models of T-cell lymphoma. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and efficacy of dual PI3K-δ, γ inhibitor, duvelisib in patients with relapsed or refractory lymphoid neoplasms: A systematic review and meta-analysis of prospective clinical trials. [2023]

7. Japan pubmed.ncbi.nlm.nih.gov

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

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

Duvelisib: First Global Approval. [2019]

9. 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]