Anakinra for CAR-T Cell Therapy Side Effects in Lymphoma

Recruiting at 1 trial location

Overseen By Bianca Santomasso, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

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 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

62 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being done to see if the investigational drug, anakinra, prevent or reverse the severe side effects caused by CAR-T cell therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is Anakinra (Kineret) safe for humans?

Anakinra, also known as Kineret, has been used safely in humans for various conditions, including rheumatoid arthritis and other inflammatory diseases. It is generally well-tolerated, but like any medication, it can have side effects, which are usually mild and manageable. ^{1 2 3 4 5}

How does the drug Anakinra differ from other treatments for CAR-T cell therapy side effects in lymphoma?

Anakinra is unique because it targets the inflammatory response by blocking interleukin-1 (a protein that can cause inflammation), which may help manage side effects like cytokine release syndrome (CRS) associated with CAR-T cell therapy. This approach is different from other treatments that primarily focus on managing symptoms after they occur rather than preventing the inflammatory process. ^{2 4 6 7 8}

Research Team

Jae Park, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

This trial is for adults over 18 with relapsed B-cell ALL, MCL, or NHL who are getting approved CD19-specific CAR T cell therapy. It's not for pregnant or breastfeeding women, those with uncontrolled infections, or anyone allergic to E. coli-derived proteins.

Inclusion Criteria

I am 18 or older with relapsed B-cell cancer and will receive approved CAR T cell therapy.

Exclusion Criteria

I am not pregnant or breastfeeding.

I do not have any uncontrolled fungal or bacterial infections.

I am not pregnant and cannot become pregnant due to surgery or being postmenopausal for 2+ years.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive anakinra to prevent or reverse severe side effects caused by CAR-T cell therapy. Cohort 1 receives anakinra 100mg s.c. every 12 hours starting on day 2 post CAR T cell infusion for 10 days. Cohort 2 receives anakinra 100mg s.c. daily starting on day 0 of T cell infusion for 7 days.

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on severe neurotoxicities and other side effects.

4 weeks

Treatment Details

Interventions

• Anakinra

Trial Overview The study tests if anakinra can prevent or treat severe side effects in patients undergoing CAR-T cell therapy for certain blood cancers like lymphomas and leukemia.

Participant Groups

Group I: Arm 1 (CART Cell Group) Experimental Treatment 1 Intervention

Cohort 1 Patients will receive anakinra 100mg s.c. every 12 hours starting on day 2 post CAR T cell infusion, or after 2 documented fevers of ≥38.5° C prior to day 2, whichever time point is earlier. Anakinra will be continued for 10 days. Cohort 2 Patients will receive anakinra 100mg s.c. daily on day 0 of T cell infusion, and continue anakinra daily for 7 days

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Findings from Research

Chimeric antigen receptor (CAR)-T cell therapy, specifically targeting CD19, has shown promising results in treating non-Hodgkin lymphomas (NHLs) resistant to standard therapies, leading to FDA and EMA approvals for tisagenlecleucel and axicabtagene ciloleucel.

While CAR-T cell therapy can cause significant adverse events like cytokine release syndrome and neurological toxicity, these effects are manageable with proper medical support, highlighting the importance of trained teams in administering this novel treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. Hopfinger, G., Jäger, U., Worel, N.[2020]

CAR T-cell therapy, particularly with anti-CD19 targeting, has shown significant effectiveness in treating aggressive B-cell non-Hodgkin's lymphoma (NHL), leading to long-term remissions in patients with diffuse large B-cell lymphoma (DLBCL) who have not responded to other treatments.

Two CAR T-cell products, axicabtagene ciloleucel and tisagenlecleucel, have been approved by the FDA for refractory DLBCL, while a third product, liso-cel, is showing promising results in ongoing trials, although potential side effects like cytokine-release syndrome and neurotoxicity are important considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. Chavez, JC., Bachmeier, C., Kharfan-Dabaja, MA.[2020]

CAR T cell therapy has shown significantly better response rates in patients with relapsed non-Hodgkin lymphoma compared to traditional salvage chemotherapy, indicating its efficacy in this challenging setting.

While CAR T therapy can lead to side effects like cytokine release syndrome and neurological events, most patients recover from these effects, suggesting a manageable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical experience of CAR T cell therapy in lymphomas. Oluwole, OO.[2022]

CAR T cell therapy, particularly with the approval of tisagenlecleucel, has shown remarkable efficacy in treating pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia, with six therapies approved as of April 2023 for B-cell malignancies and multiple myeloma.

However, the therapy is associated with significant adverse events like cytokine release syndrome, which are more severe with higher pretreatment tumor burdens; thus, initiating therapy early or using a debulking strategy may help mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From bench to bedside: the history and progress of CAR T cell therapy. Mitra, A., Barua, A., Huang, L., et al.[2023]

CAR T cell therapy is effective in treating B cell malignancies like acute lymphoblastic leukemia and non-Hodgkin lymphomas, but it can also cause serious side effects, including multi-organ failure.

Early recognition and management of side effects such as cytokine release syndrome and neurotoxicity are crucial for healthcare staff to ensure patient safety during CAR T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How I treat adverse effects of CAR-T cell therapy. Yáñez, L., Alarcón, A., Sánchez-Escamilla, M., et al.[2021]

References

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

CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]

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

Managing the toxicities of CAR T-cell therapy. [2019]

3. England pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy for B-cell lymphomas: clinical trial results of available products. [2020]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical experience of CAR T cell therapy in lymphomas. [2022]

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

From bench to bedside: the history and progress of CAR T cell therapy. [2023]

6. England pubmed.ncbi.nlm.nih.gov

How I treat adverse effects of CAR-T cell therapy. [2021]

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

CAR T-cell Therapy Yields Durable Remissions in FL. [2020]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: IBD-like colitis following CAR T cell therapy for diffuse large B cell lymphoma. [2023]