CAR-T Cells for Lymphoma and Leukemia

(PRODIGY Trial)

Overseen By Rachel Kingsford

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

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if CAR-T cells, a type of immunotherapy, can combat certain blood cancers, such as non-Hodgkin lymphoma (NHL) and specific leukemias (ALL and CLL). The research seeks to discover if these specially engineered cells can target and destroy cancer cells that have returned or resisted other treatments. The trial involves a series of steps to ensure safety and effectiveness, with participants receiving a specific type of infusion. Suitable candidates for this trial include those with relapsed or hard-to-treat CD-19 positive lymphomas or leukemias who have already tried at least two other treatments without success. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that anti-CD19 CAR-T cells have been tested for safety in people with certain blood cancers. These studies indicate that while the treatment can cause side effects, they are often manageable. Some patients have experienced significant benefits, even when other treatments didn't work.

Specifically, one study found that this therapy, called axicabtagene ciloleucel, was used for adults with hard-to-treat large B-cell lymphoma. The treatment showed good results and received FDA approval for this condition, indicating it meets safety standards for specific cases.

However, it's important to know that this is a phase 1 trial, which mainly focuses on ensuring safety and finding the right dose. This phase involves close monitoring to manage any side effects, which can include fever, tiredness, or low blood cell counts. Participants in phase 1 trials receive close observation to ensure their safety throughout the study. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for lymphoma and leukemia, which often include chemotherapy and radiation, Anti-CD19 CAR-T cell therapy offers a novel approach by using the patient's own immune cells to fight cancer. This treatment is unique because it involves engineering T cells to specifically target and destroy cancer cells that express the CD19 protein on their surface. Researchers are excited about Anti-CD19 CAR-T cells as they have shown the potential to provide long-lasting remission, even in cases that are resistant to conventional therapies. This targeted action could lead to fewer side effects compared to traditional treatments, which often affect healthy cells too.

What evidence suggests that anti-CD19 CAR-T cells might be an effective treatment for lymphoma and leukemia?

Research shows that anti-CD19 CAR-T cell therapy, which participants in this trial will receive, holds promise for treating certain blood cancers, such as non-Hodgkin lymphoma and leukemia. Studies have found that this treatment can benefit patients whose cancer has returned or hasn't responded to other treatments. Specifically, treatments like axicabtagene ciloleucel have proven effective for patients with aggressive B-cell lymphomas. This therapy uses specially modified immune cells (T cells) to target and destroy cancer cells with the CD19 protein. Early results suggest that this method can significantly reduce cancer in some patients. ^{1 2 5 6 7}

Who Is on the Research Team?

Sagar Patel, MD

Principal Investigator

Huntsman Cancer Institute/ University of Utah

Are You a Good Fit for This Trial?

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

Pregnant or breastfeeding women

I am currently being treated for an infection.

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

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

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]

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]

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