Duvelisib Maintenance for T-Cell Lymphoma

Not currently recruiting at 1 trial location

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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the drug duvelisib can help individuals with certain T-cell lymphomas (a type of blood cancer) live longer without disease progression after a stem cell transplant. Researchers aim to determine if regular use of duvelisib is safe and effective in preventing cancer recurrence. Suitable candidates have been diagnosed with specific types of T-cell lymphoma and have either just completed or are eligible for a stem cell transplant. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group, offering participants the opportunity to contribute to significant findings.

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.

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

Research has shown that duvelisib, the treatment under study, has been used for conditions like chronic lymphocytic leukemia (CLL) and has a known safety record in those cases. However, non-blood-related side effects occurred in 10% or more of patients, which are important to consider when thinking about joining a trial.

Additionally, the FDA issued a warning about a possible increased risk of death in a different trial comparing duvelisib to another drug. This indicates serious safety concerns to keep in mind, even though duvelisib has been used in people before.

In another study, patients with relapsed or hard-to-treat peripheral T-cell lymphoma (a type of blood cancer) also took duvelisib. This study provided insights into the drug's safety and its effects in these patients.

Overall, duvelisib has been studied in people before, offering some understanding of its safety. However, potential risks should be considered when deciding to join this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for T-cell lymphoma, which often include chemotherapy and stem cell transplants, duvelisib targets specific proteins called PI3K-delta and PI3K-gamma that are involved in cancer cell growth. This targeted approach allows duvelisib to potentially halt the progression of the disease with less collateral damage to healthy cells. Researchers are excited about duvelisib because it offers a promising maintenance therapy option that could improve remission rates and quality of life by reducing the need for more aggressive treatments. Additionally, duvelisib's oral administration makes it more convenient compared to intravenous therapies.

What evidence suggests that duvelisib might be an effective treatment for T-cell lymphoma?

Research has shown that duvelisib, a pill, can help treat T-cell lymphomas. Studies found that 48% of patients responded to duvelisib, with 33% showing no signs of cancer after treatment. On average, patients' cancer did not worsen for about 3.45 months. In this trial, participants will receive duvelisib maintenance therapy. Duvelisib blocks certain proteins that help cancer cells grow and survive, suggesting it could improve outcomes for people with this type of lymphoma. ^{4 5 6 7 8}

Who Is on the Research Team?

Amanda Cashen, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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, 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 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]

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3061/533672/Duvelisib-in-Patients-with-Relapsed-Refractory

Duvelisib in Patients with Relapsed/Refractory Peripheral T ... Efficacy outcomes: ORR: 48%, complete response rate (CRR): 33%, median progression-free survival (mPFS): 3.45 mo, median duration of response ( ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124058130

Duvelisib in Patients with Relapsed/Refractory Peripheral T ... Efficacy outcomes: ORR: 48%, complete response rate (CRR): 33%, median progression-free survival (mPFS): 3.45 mo, median duration of response ( ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11862811/

Duvelisib plus Romidepsin in relapsed/refractory T cell ... Duvelisib plus romidepsin showed greater efficacy at the MTD across disease subtypes, with an overall response rate (ORR) of 54% in Arm A (37% CRR, 18% PRR) ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03372057

NCT03372057 | A Study of Duvelisib in Participants With ... This is a multi-center, parallel cohort, open-label, Phase 2 study of duvelisib, an oral dual inhibitor of phosphoinositide-3-kinase-delta, gamma (PI3K-δ,γ), in ...

5. onclive.com onclive.com/view/investigators-look-to-add-duvelisib-to-treatment-arsenal-of-rare-t-cell-lymphoma-subtype

Investigators Look to Add Duvelisib to Treatment Arsenal ... Duvelisib targets PI3K-δ and PI3K-γ isoforms, showing potential in treating rare T-cell lymphoma subtypes. The phase 2 PRIMO study demonstrated ...

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. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/211155s000lbl.pdf

COPIKTRA (duvelisib) - accessdata.fda.gov The data described below reflect exposure to COPIKTRA in two single-arm, open-label clinical trials, one open-label extension clinical trial, and one randomized ...

8. fda.gov fda.gov/media/159559/download

FDA Drug Safety Communication FDA is warning that results from a clinical trial showed a possible increased risk of death with. Copiktra (duvelisib) compared to another ...