43 Participants Needed

Duvelisib After CAR T-Cell Therapy for Lymphoma

Armin Ghobadi, MD - Washington ...
Overseen ByArmin Ghobadi, M.D.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

While chimeric antigen receptor T-cell (CAR T-cell) therapy produces impressive response rates in heavily pre-treated patients, early loss of response remains a barrier. One potential mechanism of relapse is limited CAR T-cell persistence. Pre-clinical research shows that PI3K inhibition represents an intriguing mechanism for increasing CAR T-cell persistence that is easily reversible and CAR T-cell agnostic. The investigators hypothesize that PI3K inhibition with duvelisib would be safe, may provide effective prophylaxis against cytokine release syndrome (CRS), and may enhance the persistence and efficacy of CAR T-cells in the treatment of hematologic malignancies.

Will I have to stop taking my current medications?

The trial requires that you stop taking any strong CYP3A inducers or inhibitors before starting duvelisib. If you're on such medications, you'll need to discontinue them 7 days before starting duvelisib for inhibitors, 14 days for inducers, or wait for 4-5 half-lives of the drug.

Is Duvelisib safe for use in humans?

Duvelisib, also known as Copiktra, IPI-145, or INK-1197, has been studied for safety in humans. It is generally considered safe, but like many treatments, it can have side effects. Common side effects include diarrhea, low white blood cell counts, and liver enzyme changes, which are usually manageable with medical supervision.12345

How does the drug Duvelisib differ from other treatments for lymphoma after CAR T-cell therapy?

Duvelisib is unique because it is a targeted therapy that inhibits specific enzymes (PI3K-delta and PI3K-gamma) involved in the growth and survival of cancer cells, offering a different mechanism of action compared to traditional chemotherapy or CAR T-cell therapy. This makes it a potential option for patients who have not responded to or have relapsed after CAR T-cell therapy.45678

Research Team

Armin Ghobadi, MD - Washington ...

Armin Ghobadi, M.D.

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for adults over 18 with certain types of non-Hodgkin lymphoma eligible for CAR T-cell therapy, not B-cell acute lymphoblastic leukemia. Participants must understand the study and consent to it, use effective contraception, and not be pregnant or breastfeeding. They can't have allergies to duvelisib or similar drugs, uncontrolled infections, significant heart/kidney/liver disease, other cancers (except some skin cancers), active CNS involvement by malignancy, or be on strong CYP3A inducers/inhibitors.

Inclusion Criteria

I am eligible for specific FDA-approved treatments for non-Hodgkin lymphoma.
I am 18 years old or older.
I agree to use birth control during and for 3 months after the study.
See 1 more

Exclusion Criteria

I have an autoimmune disease affecting my brain or spinal cord, not related to my blood cancer.
I have a serious heart condition.
I cannot take preventive medication for certain infections.
See 17 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive duvelisib from Day -2 through Day 28 to determine the maximum tolerated dose

4 weeks
Daily dosing

Dose Expansion

Participants in Cohort A receive duvelisib from Day -2 to Day 28, and Cohort B from Day -2 to Day 180 with cycles of dosing and rest

6 months
Cycle-based visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Treatment Details

Interventions

  • Duvelisib
Trial OverviewThe trial tests if duvelisib enhances CAR T-cell persistence and efficacy in treating hematologic malignancies post-CAR T-cell therapy. It also examines whether duvelisib can prevent cytokine release syndrome safely. Patients receive this PI3K inhibitor following their standard CAR T-cell treatment.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Dose Escalation Stage: DuvelisibExperimental Treatment1 Intervention
* Duvelisib is an oral medication taken on a once or twice daily basis on all dosing days. Doses being explored in this study are 15 mg BID (starting dose), 25 mg BID, and 15 mg QD. In the dose escalation stage, patients will receive duvelisib from Day -2 through Day 28. * CAR T-cells will be given per standard of care.
Group II: Cohort B Dose Expansion Stage: DuvelisibExperimental Treatment1 Intervention
* Patients in Cohort B will receive duvelisib from Day -2 to Day 180 as follows: * Cycle 1 dosing begins on Day -2 and continues through Day 28 followed by 2 weeks off therapy * Cycles 2-6 are 28 days long and consist of dosing on Days 1 through 14, with 2 weeks off therapy. * CAR T-cells will be given per standard of care.
Group III: Cohort A Dose Expansion Stage: DuvelisibExperimental Treatment1 Intervention
* Patients in Cohort A will receive duvelisib from Day -2 to Day 28. The dose that will be given will be determined in the dose escalation stage (the maximum tolerated dose). * CAR T-cells will be given per standard of care.

Find a Clinic Near You

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+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

The Foundation for Barnes-Jewish Hospital

Collaborator

Trials
43
Recruited
6,600+

Findings from Research

In a study involving 11 patients with relapsed/refractory B-cell non-Hodgkin lymphoma, the combination of CD19 CAR-T cells and the anti-PD-1 antibody nivolumab was found to be safe, with no dose-limiting toxicities and manageable side effects like cytokine release syndrome in a minority of patients.
The treatment showed promising efficacy, achieving an objective response rate of 81.81% and a complete response rate of 45.45%, indicating strong anti-lymphoma activity that warrants further investigation in larger clinical trials.
Anti-CD19 Chimeric Antigen Receptor T Cells in Combination With Nivolumab Are Safe and Effective Against Relapsed/Refractory B-Cell Non-hodgkin Lymphoma.Cao, Y., Lu, W., Sun, R., et al.[2020]
In a study of 15 patients with relapsed or refractory diffuse large B-cell lymphoma, administering CD19-specific CAR T cells after high-dose chemotherapy and autologous stem cell transplantation resulted in a 2-year progression-free survival rate of 30%.
The treatment was associated with a high incidence of reversible neurotoxicity and cytokine release syndrome, but patients with lower levels of naive-like CD4+ and CD8+ CAR T cells showed better disease control, indicating that the immunophenotype of CAR T cells may influence treatment outcomes.
CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma.Sauter, CS., Senechal, B., Rivière, I., et al.[2021]
The review of 9 studies involving patients with relapsed/refractory hematological malignancies suggests that combining CAR-T cell therapy with PD-1/PD-L1 inhibitors may be a promising option, particularly for B-cell acute lymphoblastic leukaemia (B-ALL), although the data is still modest.
The safety profile of the combination therapy appears to be comparable to that of CAR-T cell monotherapy, indicating that it may not introduce additional risks.
Combined or Sequential Treatment with Immune Checkpoint Inhibitors and Car-T Cell Therapies for the Management of Haematological Malignancies: A Systematic Review.Pérez-Moreno, MA., Ciudad-Gutiérrez, P., Jaramillo-Ruiz, D., et al.[2023]

References

Anti-CD19 Chimeric Antigen Receptor T Cells in Combination With Nivolumab Are Safe and Effective Against Relapsed/Refractory B-Cell Non-hodgkin Lymphoma. [2020]
CD19 CAR T cells following autologous transplantation in poor-risk relapsed and refractory B-cell non-Hodgkin lymphoma. [2021]
Combined or Sequential Treatment with Immune Checkpoint Inhibitors and Car-T Cell Therapies for the Management of Haematological Malignancies: A Systematic Review. [2023]
Chimeric Antigen Receptor T-Cell Therapies for Aggressive B-Cell Lymphomas: Current and Future State of the Art. [2021]
CD19/CD22 Chimeric Antigen Receptor T Cell Cocktail Therapy following Autologous Transplantation in Patients with Relapsed/Refractory Aggressive B Cell Lymphomas. [2022]
Peri-CAR-T practice patterns and survival predictors for all CAR-T patients and post-CAR-T failure in aggressive B-NHL. [2023]
Intensive Debulking Chemotherapy Improves the Short-Term and Long-Term Efficacy of Anti-CD19-CAR-T in Refractory/Relapsed DLBCL With High Tumor Bulk. [2022]
Anti-CD19 Chimeric Antigen Receptor T Cell Therapies: Harnessing the Power of the Immune System to Fight Diffuse Large B Cell Lymphoma. [2020]