CAR-T Therapy for B-Cell Lymphoma

Recruiting at 1 trial location

Overseen By Ariela Noy

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: AIDS Malignancy Consortium

Must be taking: Antiretrovirals

Must not be taking: Corticosteroids, Immunosuppressives

Disqualifiers: Pregnancy, CNS pathology, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 day

20 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial evaluates the side effects and usefulness of axicabtagene clioleucel (a CAR-T therapy) and find out what effect, if any, it has on treating patients with HIV-associated aggressive B-cell non-Hodgkin lymphoma that has come back (relapsed) or not responded to treatment (refractory). T cells are infection fighting blood cells that can kill tumor cells. Axicabtagene ciloleucel consists of genetically modified T cells, modified to recognize CD-19, a protein on the surface of cancer cells. These CD-19-specific T cells may help the body's immune system identify and kill CD-19-positive B-cell non-Hodgkin lymphoma cells.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain treatments like corticosteroids, chemotherapy, and immunosuppressive therapies must be stopped within specific timeframes before certain procedures. It's best to discuss your current medications with the trial team to understand any necessary adjustments.

What data supports the effectiveness of the treatment Axicabtagene Ciloleucel (Axi-cel) for B-cell lymphoma?

Axicabtagene Ciloleucel (Axi-cel) has shown high response rates in patients with relapsed or refractory large B-cell lymphoma, with studies reporting significant improvements in survival compared to standard care. It is approved by the FDA for use in certain types of B-cell lymphoma after other treatments have failed. ^{1 2 3 4 5}

Is CAR-T therapy (Axicabtagene Ciloleucel) safe for humans?

CAR-T therapy, known as Axicabtagene Ciloleucel or Yescarta, has been studied for safety in treating B-cell lymphomas. Common side effects include cytokine release syndrome (a condition where the immune system is overly activated) and neurological issues, but these are generally manageable. Other side effects can include infections, fever, diarrhea, nausea, low blood pressure, and fatigue. ^{2 5 6 7 8}

How is the treatment Axicabtagene Ciloleucel unique for B-cell lymphoma?

Axicabtagene Ciloleucel is a unique treatment for B-cell lymphoma because it is a CAR T-cell therapy that uses the patient's own modified immune cells to target and destroy cancer cells, specifically those expressing the CD19 antigen. This approach is different from traditional chemotherapy as it offers a personalized and targeted treatment option for patients with relapsed or refractory B-cell lymphoma who have not responded to other therapies. ^{1 2 3 9 10}

Research Team

Ariela Noy

Principal Investigator

AIDS Malignancy Consortium

Eligibility Criteria

This trial is for adults over 18 with HIV and aggressive B-cell non-Hodgkin lymphoma that's relapsed or resistant to treatment. They must have had at least two prior therapies including an anthracycline and rituximab, be PET-positive or have bone marrow involvement, and be in fairly good health (ECOG <=1).

Inclusion Criteria

I have received anthracycline and rituximab and my disease is resistant after 2 treatments.

Agreement to use adequate contraception for women of child-bearing potential and men

Documentation of HIV-1 infection by specific means

Exclusion Criteria

Pregnant or nursing women

I do not have any uncontrolled illnesses.

I have a history of heart conditions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning

Patients receive fludarabine and cyclophosphamide intravenously to prepare for CAR-T cell therapy

3 days

3 visits (in-person)

Treatment

Patients receive axicabtagene ciloleucel intravenously

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Weekly for 1 month, monthly for 5 months, then every 3 months

Treatment Details

Interventions

• Axicabtagene Ciloleucel

Trial Overview The trial tests axicabtagene ciloleucel (CAR-T therapy), where patients' T cells are modified to target CD-19 on cancer cells. It aims to see how well these engineered T cells can treat the lymphoma.

Participant Groups

Group I: Treatment (conditioning, axicabtagene ciloleucel) Experimental Treatment 3 Interventions

Patients receive fludarabine IV over 30 minutes and cyclophosphamide IV over 1 hour on days -5, -4, and -3. Patients then receive axicabtagene ciloleucel IV over 30 minutes on day 0.

Axicabtagene Ciloleucel is already approved in United States, European Union for the following indications:

Approved in United States as Yescarta for:

• Large B-cell lymphoma that is refractory to first-line chemoimmunotherapy or that relapses within 12 months of first-line chemoimmunotherapy
• Relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy
• Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy

Approved in European Union as Yescarta for:

• Diffuse large B-cell lymphoma (DLBCL) and high-grade B-cell lymphoma (HGBL) that relapses within 12 months from completion of, or is refractory to, first-line chemoimmunotherapy
• Relapsed or refractory DLBCL and primary mediastinal large B-cell lymphoma, after two or more lines of systemic therapy
• Relapsed or refractory follicular lymphoma after three or more lines of systemic therapy

Who Is Running the Clinical Trial?

AIDS Malignancy Consortium

Lead Sponsor

Trials

64

Recruited

9,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Memorial Sloan Kettering Cancer Center

Collaborator

Trials

1,998

Recruited

602,000+

Kite, A Gilead Company

Industry Sponsor

Trials

45

Recruited

4,300+

Findings from Research

Axicabtagene ciloleucel (axi-cel) is an effective CAR T-cell therapy targeting CD19, showing high response rates and a manageable safety profile in patients with relapsed or refractory B-cell malignancies, particularly after two or more lines of prior treatment.

Axi-cel is FDA-approved for adult patients with specific types of B-cell lymphomas, including diffuse large B-cell lymphoma, and is currently being studied for its efficacy in other B-cell malignancies in ongoing clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphomas. Sharma, P., King, GT., Shinde, SS., et al.[2018]

Axicabtagene ciloleucel (axi-cel) demonstrated impressive efficacy in treating relapsed/refractory large B-cell lymphoma, with overall and complete response rates of 83% and 58%, respectively, in the pivotal ZUMA-1 trial with a median follow-up of 27.1 months.

While axi-cel shows promise, it is associated with significant toxicities, including cytokine release syndrome (CRS) in 7% to 14% of patients and immune effector cell-associated neurotoxicity syndrome (ICANS) in 31% to 55%, highlighting the need for careful patient management and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma. Halford, Z., Anderson, MK., Bennett, LL.[2021]

In a phase 2 trial involving 111 patients with refractory large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) demonstrated a high objective response rate of 82%, with 54% achieving a complete response, indicating its efficacy as a treatment option.

The treatment was associated with significant adverse events, including neutropenia in 78% of patients and neurologic events in 28%, highlighting the need for careful monitoring of safety during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. Neelapu, SS., Locke, FL., Bartlett, NL., et al.[2023]

In a phase 3 trial involving 359 patients with early relapsed or refractory large B-cell lymphoma, treatment with axicabtagene ciloleucel (axi-cel) resulted in significantly longer overall survival compared to standard care, with a median follow-up of 47.2 months showing a hazard ratio for death of 0.73 (P = 0.03).

Axi-cel also demonstrated improved progression-free survival, with a median of 14.7 months compared to 3.7 months for standard care, indicating its efficacy as a second-line treatment option for high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma. Westin, JR., Oluwole, OO., Kersten, MJ., et al.[2023]

In a retrospective study of 275 patients with relapsed/refractory large B-cell lymphoma (LBCL) receiving axicabtagene ciloleucel (axi-cel), the overall response rate was 82% and the complete response rate was 64%, demonstrating strong efficacy similar to the original ZUMA-1 trial.

Safety profiles showed that 7% of patients experienced severe cytokine release syndrome and 31% had neurotoxicity, with a nonrelapse mortality rate of 4.4%, indicating manageable risks associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. Nastoupil, LJ., Jain, MD., Feng, L., et al.[2022]

In a study of 122 patients treated with axicabtagene ciloleucel (axi-cel) for relapsed aggressive B-cell non-Hodgkin lymphoma, the overall response rate was 70% and the complete response rate was 50%, indicating strong efficacy even in a post-commercial setting with relaxed eligibility criteria.

Patients eligible for the original ZUMA-1 trial had significantly better outcomes, including higher complete response rates (63% vs. 42%) and longer duration of response, progression-free survival, and overall survival, while the rates of severe side effects like cytokine release syndrome and neurotoxicity were consistent with those observed in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. Jacobson, CA., Hunter, BD., Redd, R., et al.[2022]

Axicabtagene ciloleucel (axi-cel) is an FDA-approved CAR T-cell therapy specifically designed to target CD19, showing promise in treating relapsed or refractory aggressive non-Hodgkin's lymphomas, including diffuse large B-cell lymphoma.

While axi-cel has demonstrated significant efficacy in clinical trials (ZUMA-1 Phase I and II), it is associated with potential toxicities such as cytokine release syndrome and neurotoxicity, which pose challenges for safe administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma. Jain, MD., Bachmeier, CA., Phuoc, VH., et al.[2020]

Yescarta (axicabtagene ciloleucel) is an engineered T-cell therapy that showed a 66% overall response rate and a 47% complete response rate in treating relapsed or refractory diffuse large B-cell lymphoma, based on a phase II study with a median follow-up of 15.1 months.

The therapy was associated with manageable adverse events, including cytokine release syndrome and neurological issues, making it a promising option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. Papadouli, I., Mueller-Berghaus, J., Beuneu, C., et al.[2022]

Axicabtagene ciloleucel and tisagenlecleucel are FDA-approved CAR T cell therapies specifically designed to target CD19 in patients with relapsed or refractory aggressive B cell non-Hodgkin lymphoma, marking a significant advancement in cellular immunotherapy.

Despite their transformative potential, there are ongoing concerns about the appropriate use and potential short- and long-term toxicities of these therapies, prompting expert consensus to guide clinicians in their application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. Jain, T., Bar, M., Kansagra, AJ., et al.[2020]

In a Phase 2 study involving 17 Japanese patients with relapsed/refractory large B-cell lymphoma, axicabtagene ciloleucel (axi-cel) demonstrated a high objective response rate of 86.7%, indicating its efficacy as a treatment option.

While no dose-limiting toxicities were observed, all patients experienced grade ≥3 treatment-emergent adverse events, with the most common being neutropenia and cytokine release syndrome, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of axicabtagene ciloleucel in Japanese patients with relapsed or refractory large B-cell lymphoma. Kato, K., Makita, S., Goto, H., et al.[2022]

References

1. Spain pubmed.ncbi.nlm.nih.gov

Axicabtagene ciloleucel for the treatment of relapsed/refractory B-cell non-Hodgkin's lymphomas. [2018]

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

Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma. [2021]

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

Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. [2023]

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

Survival with Axicabtagene Ciloleucel in Large B-Cell Lymphoma. [2023]

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

Standard-of-Care Axicabtagene Ciloleucel for Relapsed or Refractory Large B-Cell Lymphoma: Results From the US Lymphoma CAR T Consortium. [2022]

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

Axicabtagene Ciloleucel in the Non-Trial Setting: Outcomes and Correlates of Response, Resistance, and Toxicity. [2022]

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

Axicabtagene ciloleucel (KTE-C19), an anti-CD19 CAR T therapy for the treatment of relapsed/refractory aggressive B-cell non-Hodgkin's lymphoma. [2020]

8. England pubmed.ncbi.nlm.nih.gov

EMA Review of Axicabtagene Ciloleucel (Yescarta) for the Treatment of Diffuse Large B-Cell Lymphoma. [2022]

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

Use of Chimeric Antigen Receptor T Cell Therapy in Clinical Practice for Relapsed/Refractory Aggressive B Cell Non-Hodgkin Lymphoma: An Expert Panel Opinion from the American Society for Transplantation and Cellular Therapy. [2020]

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

Phase 2 study of axicabtagene ciloleucel in Japanese patients with relapsed or refractory large B-cell lymphoma. [2022]