CAR-T Cells for Lymphoma and Leukemia

(PRODIGY Trial)

Overseen By Catherine Cromar

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Utah

Must not be taking: Immunosuppressants, Investigational agents

Disqualifiers: Active infection, Autoimmune disease, Pregnancy, 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: Unknown

6 Participants Needed

Trial Summary

What is the purpose of this trial?

This is an open label, non-randomized, phase 1 study of anti-CD19 CAR-T cells against relapsed CD19 positive NHL, CLL and ALL based in a lymphodepletion regimen (fludarabine and cyclophosphamide) and using a CellReGen-based process for manufacturing CAR-T cells. This study will utilize a staggered enrollment design with a safety observation period.

Will I have to stop taking my current medications?

The trial protocol mentions that participants must follow washout periods for certain medications, but it does not specify which ones. You may need to stop some medications before starting the trial, so it's best to discuss this with the study team.

What data supports the effectiveness of the treatment Anti-CD19 CAR-T cells, Axicabtagene ciloleucel, Tisagenlecleucel, Lisocabtagene maraleucel, Yescarta, Kymriah for lymphoma and leukemia?

Research shows that Anti-CD19 CAR-T cell therapy, including treatments like Axicabtagene ciloleucel and Tisagenlecleucel, has significantly improved outcomes for patients with aggressive B-cell lymphomas, increasing cure rates from 10% to 40%. These therapies are now considered standard care for certain types of relapsed or refractory lymphomas, offering a promising option for patients who have not responded to other treatments. ^{1 2 3 4 5}

Is CAR-T cell therapy safe for humans?

CAR-T cell therapies, like axicabtagene ciloleucel and tisagenlecleucel, have been approved for certain types of lymphoma and leukemia, and while they show good results, they can also cause side effects. These side effects can include reactions like fever, low blood pressure, and neurological issues, so careful monitoring is needed after treatment. ^{1 5 6 7 8}

How is the CAR-T cell treatment for lymphoma and leukemia different from other treatments?

CAR-T cell treatment is unique because it uses a patient's own modified immune cells to specifically target and attack cancer cells, offering a new option for those with aggressive B-cell lymphomas that don't respond to traditional therapies. This personalized approach can lead to long-lasting remissions in cases where other treatments have failed. ^{1 3 5 8 9}

Research Team

Sagar Patel, MD

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Eligibility Criteria

This trial is for people with certain blood cancers (like Non-Hodgkin's Lymphoma and Acute Lymphoblastic Leukemia) that have come back or didn't respond to treatment. Participants should have cancer cells with a marker called CD19. Specific eligibility details are not provided, but typically include health status and prior treatments.

Inclusion Criteria

My cancer is CD-19 positive and includes conditions like NHL, ALL, or CLL.

My condition did not improve after 2 or more treatments.

My liver function tests are within the normal range.

Exclusion Criteria

I am currently being treated for an infection.

Pregnant or breastfeeding women

I haven't had cancer treatment or experimental therapy in the last 14 days or within five half-lives of the treatment.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo a lymphodepletion regimen with fludarabine and cyclophosphamide prior to CAR-T cell infusion

1 week

CAR-T Cell Infusion

Participants receive anti-CD19 CAR-T cell infusion

1 day

Safety Observation

Participants are observed for safety and toxicity within 28 days post CAR-T administration

4 weeks

Follow-up

Participants are monitored for disease-free survival and overall survival up to 12 months post CAR-T administration

12 months

Treatment Details

Interventions

• Anti-CD19 CAR-T cells

Trial Overview The study tests CAR-T cell therapy, where patients' immune cells are engineered to fight their CD19 positive cancer after a pre-treatment with fludarabine and cyclophosphamide. It's an early-phase trial assessing safety of the manufactured CAR-T cells using CellReGen technology.

Participant Groups

Group I: Anti-CD19 CAR-T Cell Infusion Experimental Treatment 1 Intervention

Anti-CD19 CAR-T cells is already approved in United States, European Union for the following indications:

Approved in United States as Yescarta for:

• Diffuse large B-cell lymphoma
• Primary mediastinal large B-cell lymphoma
• High-grade B-cell lymphoma

Approved in United States as Kymriah for:

• Acute lymphoblastic leukemia
• Diffuse large B-cell lymphoma

Approved in European Union as Yescarta for:

• Diffuse large B-cell lymphoma
• Primary mediastinal large B-cell lymphoma
• High-grade B-cell lymphoma

Approved in European Union as Kymriah for:

• Acute lymphoblastic leukemia
• Diffuse large B-cell lymphoma

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

Findings from Research

The three CAR-T cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) show promising efficacy in treating large B cell lymphoma, with overall response rates of nearly 70% and complete response rates exceeding 50% across 33 studies involving 2,172 patients.

However, axicabtagene ciloleucel and tisagenlecleucel are associated with significant risks of severe neurotoxicity and life-threatening cytokine release syndrome, necessitating careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. Meng, J., Wu, X., Sun, Z., et al.[2022]

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]

CAR T-cell therapies have significantly changed treatment options for patients with relapsed or refractory aggressive B-cell lymphomas, with three products currently approved or nearing approval.

Selecting the right CAR T-cell product for a patient involves careful consideration of various factors, including the patient's age, health status, previous treatments, and the specific characteristics of each CAR T-cell product.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient selection for chimeric antigen receptor (CAR) T-cell therapy for aggressive B-cell non-Hodgkin lymphomas. Johnson, PC., Abramson, JS.[2021]

CAR T-cell therapy targeting CD19 has significantly improved cure rates for relapsed or refractory aggressive B-cell lymphomas, increasing from 10% to 40% with the use of approved products like axicabtagene ciloleucel and tisagenlecleucel.

There is emerging evidence supporting the use of anti-CD19 CAR T-cell therapy in previously considered incurable conditions like indolent B-cell lymphomas and chronic lymphocytic leukemia, with ongoing trials exploring new treatment strategies and combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for B-Cell non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Clinical Trials and Real-World Experiences. Vitale, C., Strati, P.[2023]

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]

CAR-T cell therapies, specifically axicabtagene ciloleucel and tisagenlecleucel, have significantly improved outcomes for patients with relapsed or refractory aggressive B-cell lymphomas, with approvals based on pivotal trials demonstrating their efficacy after multiple prior treatments.

Despite their similar CAR technologies, differences in manufacturing and clinical trial designs exist between these therapies, highlighting the need for ongoing monitoring of patient responses and potential long-term side effects in real-world settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. Westin, JR., Kersten, MJ., Salles, G., et al.[2022]

Cytokine release syndrome (CRS) is the most common adverse reaction reported after CAR-T therapy, with significantly higher reports for axicabtagene ciloleucel compared to tisagenlecleucel, indicating a need for careful monitoring of this side effect.

The study analyzed 1426 reports of adverse drug reactions from real clinical settings, supporting the overall safety profile of CAR-T therapies while confirming CRS as a major concern.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. Bonaldo, G., Montanaro, N., AlbertoVaccheri, ., et al.[2021]

Two CAR T cell therapies, Tisagenlecleucel and Axicabtagene ciloleucel, have been approved for treating specific types of blood cancers, including B-cell acute lymphoblastic leukemia and large B-cell lymphoma, in patients who have not responded to other treatments.

This review emphasizes the importance of recognizing and managing the toxicities associated with CAR T cell therapies, while also suggesting future strategies to reduce these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Toxicity: Current Management and Future Directions. Yáñez, L., Sánchez-Escamilla, M., Perales, MA.[2020]

Anti-CD19 CAR T-cell therapy has shown remarkable efficacy in treating relapsed or refractory aggressive B-cell lymphomas, leading to durable remissions in patients who previously had no effective treatment options.

Three CAR T-cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) are approved for use, each differing in their design, manufacturing processes, and safety profiles, highlighting the need for personalized approaches in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. Abramson, JS.[2021]

References

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

Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. [2022]

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

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

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

Patient selection for chimeric antigen receptor (CAR) T-cell therapy for aggressive B-cell non-Hodgkin lymphomas. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for B-Cell non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia: Clinical Trials and Real-World Experiences. [2023]

5. 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]

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

Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. [2022]

7. Germany pubmed.ncbi.nlm.nih.gov

Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. [2021]

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

CAR T Cell Toxicity: Current Management and Future Directions. [2020]

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

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. [2021]