Duvelisib for Diffuse Large B-Cell Lymphoma

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Edmund Waller, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Waitlist Available

Sponsor: Emory University

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests if a new treatment can improve immune cells in patients with hard-to-treat lymphoma before using these cells for a special cancer treatment. The goal is to make the immune cells stronger and more effective against cancer.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop all current medications. However, you cannot be on immunosuppressive therapy, including steroids, or any other investigational drugs. Also, you should not have had chemotherapy or radiotherapy within 2 weeks before starting the study. If you are taking medications that are strong inhibitors or inducers of CYP3A, you must stop them at least 2 weeks before the trial.

What data supports the idea that Duvelisib for Diffuse Large B-Cell Lymphoma is an effective treatment?

The available research does not provide specific data on the effectiveness of Duvelisib for Diffuse Large B-Cell Lymphoma. Instead, it focuses on another treatment called tisagenlecleucel, which has shown promising results. In the JULIET trial, tisagenlecleucel led to complete responses in 32% of patients after three months, and 30% after six months. This suggests that tisagenlecleucel may be an effective treatment for this condition, but there is no direct data on Duvelisib's effectiveness for Diffuse Large B-Cell Lymphoma in the provided information. ^{1 2 3 4 5}

What safety data is available for Duvelisib in treating Diffuse Large B-Cell Lymphoma?

The provided research does not contain safety data for Duvelisib (also known as Copiktra, IPI-145, or INK-1197) in the treatment of Diffuse Large B-Cell Lymphoma. Instead, it focuses on the safety and efficacy of Tisagenlecleucel (also known as Kymriah, CTL019, CART-19, or tisa-cel), a different treatment for relapsed/refractory large B-cell lymphoma. Tisagenlecleucel has been associated with manageable safety profiles, with reported toxicities including cytokine release syndrome and neurotoxicity. However, no specific safety data for Duvelisib in this context is mentioned in the research provided. ^{2 3 6 7 8}

Is the drug Duvelisib a promising treatment for Diffuse Large B-Cell Lymphoma?

Duvelisib is a promising drug because it has shown positive results in treating various types of blood cancers, including lymphoma. It works by targeting specific proteins that help cancer cells grow, and it has been effective in patients who have not responded to other treatments. The drug has been approved for use in certain types of lymphoma and is being further studied for its potential benefits. ^{9 10 11 12 13}

Research Team

Edmund Waller, MD

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

This trial is for adults with relapsed/refractory diffuse large B-cell lymphoma. Participants must be in good physical condition (ECOG < 2), have normal organ function, and not be pregnant or breastfeeding. They should agree to use effective contraception and not donate blood or organs during the study. People with CNS lymphoma involvement, autoimmune diseases, active infections, recent immunosuppressive therapy, or prior CD19 directed therapy are excluded.

Inclusion Criteria

I practice total abstinence as a form of contraception.

An absolute neutrophil count (ANC) > 1,000/mm^3

I finished all treatments for my DLBCL at least 2 weeks ago.

Exclusion Criteria

I am currently being treated for a serious infection.

I have had treatment targeting CD19 before.

I have a positive hepatitis B core antibody but my hepatitis B virus DNA is negative.

Treatment Details

Interventions

• Duvelisib (PI3K Inhibitor)
• Tisagenlecleucel (CAR T-cell Therapy)

Trial Overview The DEEP T CELLS Study is testing whether taking duvelisib before manufacturing CAR-T cells can improve the immune profiles of T cells in patients with difficult-to-treat diffuse large B-cell lymphoma. Duvelisib is an oral drug that may make T cells more efficient for later CAR-T cell treatment.

Participant Groups

Group I: Treatment (duvelisib) Experimental Treatment 2 Interventions

Patients receive duvelisib PO BID for 2 weeks prior to collection of CAR-T cells in the absence of disease progression or unacceptable toxicity. Patients then receive tisagenlecleucel via infusion.

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Dr. R. Donald Harvey

Emory University

Chief Medical Officer

MD from Emory University School of Medicine

Dr. George Painter

Emory University

Chief Executive Officer since 2013

PhD in Synthetic Organic Chemistry from Emory University

Novartis

Industry Sponsor

Trials

1,646

Recruited

2,778,000+

Vasant Narasimhan

Novartis

Chief Executive Officer since 2018

MD from Harvard Medical School, Bachelor's in Biological Sciences from University of Chicago, Master's in Public Policy from John F. Kennedy School of Government

Shreeram Aradhye

Novartis

Chief Medical Officer since 2022

MD from Yale University, MSc in Clinical Epidemiology from University of Pennsylvania

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Dr. Douglas R. Lowy

National Cancer Institute (NCI)

Chief Executive Officer since 2023

MD from New York University School of Medicine

Dr. Monica Bertagnolli

National Cancer Institute (NCI)

Chief Medical Officer since 2022

MD from Harvard Medical School

Secura Bio, Inc.

Industry Sponsor

Trials

9

Recruited

200+

Findings from Research

In the phase II JULIET trial, the CAR T-cell therapy tisagenlecleucel targeting CD19 demonstrated durable responses in patients with relapsed and refractory diffuse large B-cell lymphoma, with 32% achieving complete responses at 3 months.

The efficacy remained stable at 6 months, with 30% of patients still showing complete responses, indicating the potential long-term effectiveness of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Value in Using CAR T Cells for DLBCL. [2019]

In the JULIET trial, tisagenlecleucel showed high efficacy in 7 patients with relapsed or refractory diffuse large B-cell lymphoma who achieved complete response after bridging therapy, with all patients remaining in complete response at 3 months and 5 out of 7 remaining progression-free for over 12 months.

The safety profile of tisagenlecleucel was consistent with the overall trial population, with manageable adverse events including cytokine release syndrome in 4 patients, none of whom required additional treatment for CRS, suggesting a favorable safety profile for this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel in relapsed/refractory diffuse large B-cell lymphoma patients without measurable disease at infusion. Bishop, MR., Maziarz, RT., Waller, EK., et al.[2020]

Recent phase 3 clinical trials have shown that CD19-directed CAR T cell therapies, specifically axicabtagene ciloleucel and lisocabtagene maraleucel, significantly improve outcomes in patients with relapsed/refractory aggressive diffuse large B cell lymphoma compared to standard treatments, while tisagenlecleucel did not demonstrate a similar benefit.

The FDA has approved axicabtagene ciloleucel and lisocabtagene maraleucel for use in patients whose lymphoma is refractory to first-line chemoimmunotherapy or who relapse within 12 months, marking a significant advancement in treatment options for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of CD19 Chimeric Antigen Receptor T Cells in Second-Line Large B Cell Lymphoma: Lessons from Phase 3 Trials. An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. Perales, MA., Anderson, LD., Jain, T., et al.[2023]

CAR T cell therapy, specifically tisagenlecleucel, has significantly improved treatment outcomes for patients with relapsed or refractory diffuse large B cell lymphoma, showcasing its efficacy in this challenging condition.

The review also highlights the importance of understanding the biological mechanisms of tisagenlecleucel and its comparison to other CAR T therapies, as well as the financial considerations and ongoing clinical trials that may influence future treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating tisagenlecleucel and its potential in the treatment of relapsed or refractory diffuse large B cell lymphoma: evidence to date. Zavras, PD., Wang, Y., Gandhi, A., et al.[2020]

Tisagenlecleucel significantly improves overall survival (OS) in adults with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL), with a median OS of 12.48 months compared to just 4.34 to 4.40 months for historical treatments.

The overall response rate (ORR) for tisagenlecleucel was also significantly higher, showing a 36% improvement compared to historical treatments, indicating its efficacy as a treatment option for r/r DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indirect comparison of tisagenlecleucel and historical treatments for relapsed/refractory diffuse large B-cell lymphoma. Maziarz, RT., Zhang, J., Yang, H., et al.[2022]

In a study of 91 patients with relapsed/refractory large B-cell lymphoma (LBCL), treatment with the CAR T-cell therapy tisagenlecleucel (tisa-cel) resulted in a best overall response rate of 60% and a complete response rate of 32%, indicating its efficacy in a real-world setting.

The safety profile of tisa-cel was manageable, with only 5% of patients experiencing severe cytokine release syndrome and 1% experiencing neurotoxicity, suggesting that it can be safely administered in standard-of-care settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma. Iacoboni, G., Villacampa, G., Martinez-Cibrian, N., et al.[2021]

In a study of 119 patients with relapsed/refractory diffuse large B-cell lymphoma, tisagenlecleucel (tisa-cel) was associated with a significantly shorter hospital stay compared to axicabtagene ciloleucel (axi-cel), with mean inpatient stays of 11.3 days versus 18.3 days.

Tisa-cel also resulted in lower healthcare costs during both the infusion and follow-up periods, with non-CAR-T costs of $27,594.8 compared to $51,378.3 for axi-cel during infusion, indicating a more cost-effective option without compromising safety, as adverse event rates were similar for both therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world healthcare resource utilization and costs associated with tisagenlecleucel and axicabtagene ciloleucel among patients with diffuse large B-cell lymphoma: an analysis of hospital data in the United States. Maziarz, RT., Yang, H., Liu, Q., et al.[2022]

Chimeric antigen receptor (CAR) T cell therapies, specifically axicabtagene ciloleucel and tisagenlecleucel, have been approved for treating large B-cell lymphomas after two prior therapies, showing durable remissions in 30% to 40% of patients.

While these therapies are effective, they can cause serious side effects like cytokine release syndrome and neurotoxicity, necessitating treatment in specialized medical centers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translating anti-CD19 CAR T-cell therapy into clinical practice for relapsed/refractory diffuse large B-cell lymphoma. Chow, VA., Shadman, M., Gopal, AK.[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 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. United States pubmed.ncbi.nlm.nih.gov

Value in Using CAR T Cells for DLBCL. [2019]

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

Tisagenlecleucel in relapsed/refractory diffuse large B-cell lymphoma patients without measurable disease at infusion. [2020]

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

Role of CD19 Chimeric Antigen Receptor T Cells in Second-Line Large B Cell Lymphoma: Lessons from Phase 3 Trials. An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. [2023]

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

Evaluating tisagenlecleucel and its potential in the treatment of relapsed or refractory diffuse large B cell lymphoma: evidence to date. [2020]

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

Indirect comparison of tisagenlecleucel and historical treatments for relapsed/refractory diffuse large B-cell lymphoma. [2022]

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

Real-world evidence of tisagenlecleucel for the treatment of relapsed or refractory large B-cell lymphoma. [2021]

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

Real-world healthcare resource utilization and costs associated with tisagenlecleucel and axicabtagene ciloleucel among patients with diffuse large B-cell lymphoma: an analysis of hospital data in the United States. [2022]

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

Translating anti-CD19 CAR T-cell therapy into clinical practice for relapsed/refractory diffuse large B-cell lymphoma. [2022]

9. 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]

10. Japan pubmed.ncbi.nlm.nih.gov

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

11. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Duvelisib: First Global Approval. [2019]

13. 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]