Itacitinib + CAR T-Cell Therapy for Lymphoma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must not be taking: Chronic steroids, CYP3A4 inhibitors

Disqualifiers: Cardiac disease, HIV, Hepatitis, 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 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

27 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to assess the safety and efficacy of once daily itacitinib oral administration in participants with diffuse large B-cell lymphoma (DLBCL) who will receive CAR-T cell therapy with axicabtagene ciloleucel (axi-cel).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot take strong inhibitors of CYP3A4. You should discuss any medications you are taking with the study team to ensure they don't interfere with the trial.

What data supports the effectiveness of the treatment Itacitinib + CAR T-Cell Therapy for Lymphoma?

CAR T-cell therapy has shown promising results in treating relapsed or refractory B-cell lymphomas, with high response rates and durable outcomes. This therapy is effective even in cases where traditional chemotherapy has failed, and it is now a standard treatment for aggressive non-Hodgkin's Lymphoma after other treatments have been tried. ^{1 2 3 4 5}

How is the Itacitinib + CAR T-Cell Therapy treatment different from other treatments for lymphoma?

This treatment combines Itacitinib, a drug that may help reduce inflammation, with CAR T-cell therapy, a cutting-edge approach that uses modified immune cells to target and destroy cancer cells. The combination aims to enhance the effectiveness of CAR T-cell therapy by potentially reducing resistance and improving outcomes in lymphoma patients. ^{1 2 3 6 7}

Research Team

Michael Jain, MD, PhD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

Adults with diffuse large B-cell lymphoma planning to receive CAR-T cell therapy at Moffitt Cancer Center, who can't have stem cell transplants due to active lymphoma. They must understand and consent to the study, meet certain blood test criteria, agree to use contraception, and not be pregnant or nursing. Excluded are those with prior CAR-T therapy, severe itacitinib reactions, strong CYP3A4 inhibitors usage, uncontrolled infections or cardiac disease, unstable arrhythmias on medication within 2 weeks of screening.

Inclusion Criteria

I agree to use birth control during the study.

I am eligible for a specific immune therapy for my lymphoma.

Must have ability to comprehend and the willingness to sign written informed consent for study participation

Exclusion Criteria

I am not taking strong CYP3A4 inhibitors.

I currently have an untreated infection.

I have active or chronic hepatitis B.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-Modulation Treatment

Participants receive itacitinib 200 mg PO QD starting at time of apheresis approximately 4-6 weeks prior to CAR-T-cell therapy and continue until Day 30 post-CAR-T-cell therapy

4-6 weeks

CAR-T-cell Therapy

Participants receive a single infusion of axi-cel therapy on Day 0

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment, including incidence of severe CRS and ICANS

3 months

Long-term Follow-up

Participants are monitored for overall survival and progression-free survival

up to 27 months

Treatment Details

Interventions

• Itacitinib

Trial Overview The trial is testing the safety and effectiveness of taking a daily oral dose of itacitinib before receiving axicabtagene ciloleucel (axi-cel) CAR-T cell therapy for treating diffuse large B-cell lymphoma. It aims to see if pre-modulating with itacitinib improves outcomes.

Participant Groups

Group I: Pre-Modulation Treatment Experimental Treatment 2 Interventions

Participants will receive itacitinib 200 mg PO QD beginning at time of apheresis approximately 4-6 weeks prior to CAR-T-cell therapy and will continue until Day 30 (30 Days Post-CAR-T-cell therapy)

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Incyte Corporation

Industry Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Findings from Research

CD19CAR T cells have shown promising results in treating aggressive B-lineage cancers, but their effectiveness can be limited by the loss of the targeted CD19 antigen, leading to treatment failure.

The newly developed adapter CAR T cell technology (AdCAR) allows for multitargeting of different antigens, such as CD20 and CD22, which can enhance the anti-cancer activity and potentially overcome issues related to antigen loss in lymphoma treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas. Atar, D., Mast, AS., Scheuermann, S., et al.[2022]

CAR T-cell therapy is an important treatment option for patients with refractory or relapsed diffuse large B-cell lymphoma, providing a targeted approach to combat this aggressive cancer.

The review discusses the criteria for selecting patients for CAR T-cell therapy and emphasizes the importance of bridging therapy and timing to improve treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for the management of refractory/relapsed high-grade B-cell lymphoma: a practical overview. Mohty, M., Dulery, R., Gauthier, J., et al.[2023]

Anti-CD19-directed CAR T cell therapy has shown significant efficacy in treating relapsed or refractory B-cell malignancies, leading to the approval of tisagenlecleucel (Kymriah) for B-ALL in 2018 and for aggressive B-cell lymphoma shortly thereafter.

The review highlights ongoing research into resistance mechanisms and the exploration of new target antigens, indicating a continued effort to improve treatment outcomes for patients with CD19 positive B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. Balke-Want, H., Borchmann, P.[2021]

CAR T-cell therapy targeting CD19 has transformed the treatment landscape for relapsed or refractory B-cell lymphomas, leading to rapid FDA approval for multiple lymphoma subtypes due to high response rates and durability.

Three second-generation anti-CD19 CAR T-cell products have been approved for use in aggressive non-Hodgkin's lymphoma, and ongoing research is focused on understanding treatment failures and improving outcomes for patients who do not respond to therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphoma. Denlinger, N., Bond, D., Jaglowski, S.[2022]

The addition of the anti-CD20 monoclonal antibody rituximab to standard therapies has significantly improved overall survival rates in newly diagnosed diffuse large B-cell lymphoma (DLBCL).

Innovative T-cell redirecting therapies, such as bispecific antibodies targeting both T-cell and B-cell antigens, have shown impressive efficacy in heavily pre-treated patients with relapsed/refractory B-cell non-Hodgkin lymphoma, leading to ongoing clinical trials exploring their combinations with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cell redirecting therapies for B-cell non-Hodgkin lymphoma: recent progress and future directions. Russler-Germain, DA., Ghobadi, A.[2023]

CAR T-cell therapy is becoming a groundbreaking treatment for aggressive non-Hodgkin B-cell lymphoma, showing promise in improving patient outcomes.

The review discusses not only the efficacy of CAR T-cell therapy but also highlights the potential short- and long-term toxicities associated with the treatment, emphasizing the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. Hamilton, MP., Miklos, DB.[2023]

CD19-directed CAR T-cell therapy has shown promising results in treating relapsed/refractory B-cell non-Hodgkin lymphoma, with 30-40% of patients achieving durable responses in pivotal phase I/II trials, leading to FDA and EMA approvals for specific therapies.

Despite its effectiveness, the therapy is associated with significant toxicities, such as cytokine release syndrome and neurotoxicity, which can limit its use and present challenges in patient management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-directed CAR T-cell therapy in B-cell NHL. Kersten, MJ., Spanjaart, AM., Thieblemont, C.[2021]

References

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

Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas. [2022]

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

CAR T-cell therapy for the management of refractory/relapsed high-grade B-cell lymphoma: a practical overview. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

[CAR T-cell therapy for malignant B-cell lymphoma : A new treatment paradigm]. [2021]

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

CAR T-cell therapy for B-cell lymphoma. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

T-cell redirecting therapies for B-cell non-Hodgkin lymphoma: recent progress and future directions. [2023]

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

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. [2023]

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

CD19-directed CAR T-cell therapy in B-cell NHL. [2021]