CAR T Cells for Blood Cancers

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Roswell Park Cancer Institute

Must not be taking: T cell suppressive therapy

Disqualifiers: Pregnancy, HIV, Hepatitis B, others

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

Compensation: Varies

Number of Visits: 9

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using modified immune cells called EGFRt/19-28z/IL-12 CAR T cells, also known as Armored CAR T Cells, to combat certain blood cancers that have returned or not responded to previous treatments. The focus is on cancers that produce a protein called CD19. The trial aims to determine the safety and optimal dosage of these engineered cells. Patients with specific blood cancers, such as diffuse large B-cell lymphoma or chronic lymphocytic leukemia, who have already tried other treatments, might be suitable candidates. As a Phase 1 trial, this research seeks to understand how the treatment works in people, offering patients the opportunity to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on systemic T cell suppressive therapy for conditions like active graft versus host disease or autoimmune disease, you would be ineligible for the trial. It's best to discuss your specific medications with the trial team.

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

Studies have shown that a new treatment, called EGFRt/19-28z/IL-12 CAR T cells, might be safe and tolerable for treating blood cancer that has returned after treatment or did not initially respond. These specially engineered cells are designed to find and attack cancer cells more effectively. They also contain a gene that enhances the immune system's ability to fight cancer.

Although this is an early-stage trial, its existence suggests some initial belief in the treatment's safety. Researchers aim to enhance effectiveness by adding the IL-12 gene without causing severe side effects. However, as with any early-stage trial, much remains to be learned about its safety in humans, and monitoring for negative effects is crucial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about EGFRt/19-28z/IL-12 CAR T cells for treating blood cancers because they use a unique approach by engineering a patient's own immune cells to better recognize and attack cancer cells. Unlike traditional treatments like chemotherapy or radiation, which target both cancerous and healthy cells, CAR T cells specifically target cancer cells, potentially reducing side effects. Additionally, this treatment includes a special component, IL-12, which boosts the immune response, potentially enhancing effectiveness against cancer. For patients in Cohort B, the treatment is combined with a conditioning regimen, which may further improve outcomes by preparing the body to better accept and utilize the engineered CAR T cells.

What evidence suggests that EGFRt/19-28z/IL-12 CAR T cells might be an effective treatment for blood cancers?

Studies have shown that CAR T-cell therapy effectively treats blood cancers. CAR T-cells are special immune cells modified to better find and attack cancer cells. This trial tests a new type of CAR T-cell, EGFRt/19-28z/IL-12 CAR T Cells, which includes a gene for IL-12. IL-12 strengthens the immune system and might enhance the treatment's effectiveness against cancer. Previous research suggests that adding IL-12 could improve how well these modified T-cells fight cancer. Overall, CAR T-cell therapy has made significant progress in treating blood cancers effectively. ^{1 2 5 6 7}

Who Is on the Research Team?

Francisco J. Hernandez-ILizaliturri

Principal Investigator

Roswell Park Cancer Institute

Are You a Good Fit for This Trial?

This trial is for patients with certain blood cancers (like lymphoma or leukemia) that have a protein called CD19 and haven't improved after treatment or have come back. Participants need to be in good physical shape, with no major heart, lung, kidney, liver, or mental health issues.

Inclusion Criteria

I have at least one cancer lesion that shows up on a PET scan.

AST and ALT ≤ 3 x upper limit of normal (ULN) (unless related to disease)

My oxygen levels are 90% or higher on room air.

Exclusion Criteria

I have not had a heart attack in the last 6 months.

Unwilling or unable to follow protocol requirements

I have severe heart failure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Multiple visits for ECHO/MUGA, CT/PET, and biopsies

Leukapheresis

Patients undergo leukapheresis to collect T cells for modification

1 day

1 visit (in-person)

Lymphodepletion Chemotherapy

Patients receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine

3 days

3 visits (in-person)

CAR T-cell Infusion

Patients receive EGFRt/19-28z/IL-12 CAR T cells intravenously

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

Weekly for 4 weeks, every 4 weeks until 24 months, every 3 months for 1 year, then annually

What Are the Treatments Tested in This Trial?

Interventions

• EGFRt/19-28z/IL-12 CAR T Cells

Trial Overview The study tests genetically modified immune cells (EGFRt/19-28z/IL-12 CAR T cells) to see if they're safe and effective against these CD19+ blood cancers. It's an early-phase trial to find the right dose of these engineered T cells that are infused back into the patient.

How Is the Trial Designed?

Group I: Cohort B (EGFRt/19- 28z/IL-12 CAR T cells, conditioning) Experimental Treatment 12 Interventions

Patients undergo leukapheresis prior to treatment and receive lymphodepletion chemotherapy with cyclophosphamide IV over 2 hours and fludarabine IV over 30 minutes on days -5, -4, and -3. Patients then receive EGFRt/19- 28z/IL-12 CAR T cells IV over 5 to 30 minutes on day 0. Patients also undergo ECHO or MUGA during screening. Patients also undergo CT or PET as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial. Additionally, patients undergo a tissue biopsy during screening and on the trial.

Group II: Cohort A (EGFRt/19- 28z/IL-12 CAR T cells) Experimental Treatment 10 Interventions

Patients undergo leukapheresis prior to treatment. Patients receive EGFRt/19- 28z/IL-12 CAR T cells IV over 5 to 30 minutes on day 0. Patients also undergo ECHO or MUGA during screening. Patients also undergo CT or PET as well as bone marrow biopsy and aspiration and blood sample collection throughout the trial. Additionally, patients undergo a tissue biopsy during screening and on the trial.

Who Is Running the Clinical Trial?

Roswell Park Cancer Institute

Lead Sponsor

Trials

427

Recruited

40,500+

Published Research Related to This Trial

CAR-T cell therapy has shown significant success in treating CD19-positive B-cell cancers, but this review explores its potential in other blood cancers, particularly Hodgkin's lymphoma and acute myeloid leukemia.

The focus on hematologic malignancies beyond CD19 highlights the expanding applications of CAR-T cell technology, suggesting it may be effective for a broader range of blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T cells beyond CD19, UnCAR-Ted territory. Leick, MB., Maus, MV.[2020]

In a Phase I clinical trial, 19-28z CAR T-cell therapy achieved an impressive 88% complete remission rate in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), demonstrating its efficacy as a treatment option.

While the therapy can lead to severe cytokine release syndrome (sCRS), it can be effectively managed with tocilizumab without compromising the treatment's benefits, unlike high-dose steroids which can negate the positive effects of CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cancer CARtography: charting out a new approach to cancer immunotherapy. Patel, JM., Dale, GA., Vartabedian, VF., et al.[2021]

In a study involving five adults with relapsed B cell acute lymphoblastic leukemia (B-ALL), treatment with autologous T cells modified to express a CD19-specific CAR (19-28z) led to rapid tumor eradication and complete remissions without minimal residual disease (MRD), indicating strong efficacy of this therapy.

The treatment was generally well tolerated, although patients with higher tumor burdens experienced significant cytokine elevations, which required management with steroids, highlighting the need for monitoring and potential intervention during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Brentjens, RJ., Davila, ML., Riviere, I., et al.[2023]

Adoptive cellular therapy using CAR-modified T cells targeting CD19 has shown significant clinical efficacy in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in both children and adults, with some patients also benefiting from treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma (B-NHL).

Current research is expanding the use of CAR T-cell therapies to other cancers, including multiple myeloma and solid tumors, while also addressing challenges such as severe cytokine release syndrome and neurologic toxicities associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells. Geyer, MB., Brentjens, RJ.[2022]

The combination of carcinoembryonic antigen (CEA) specific CAR-T cells with recombinant human IL-12 (rhIL-12) significantly enhances the activation, proliferation, and cytotoxicity of CAR-T cells against solid tumors, as shown in both in vitro and in vivo studies.

In vivo experiments demonstrated that CEA-CAR-T cells combined with rhIL-12 exhibited superior anti-tumor activity against various solid tumors, including colorectal, pancreatic, and gastric cancers, compared to CEA-CAR-T cells alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Significantly increased anti-tumor activity of carcinoembryonic antigen-specific chimeric antigen receptor T cells in combination with recombinant human IL-12. Chi, X., Yang, P., Zhang, E., et al.[2021]

CAR T cell therapy, specifically targeting the CD19 antigen, has shown high response rates in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), indicating its potential as a new treatment option.

Despite its effectiveness, CAR T cell therapy is associated with severe toxicities like cytokine release syndrome and neurotoxicity, which pose challenges for its widespread use and highlight the need for ongoing improvements in the technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice. Luskin, MR., DeAngelo, DJ.[2018]

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 emerging as a promising immunotherapy for hematological cancers, particularly by targeting immune checkpoint proteins on tumor cells.

The review discusses various CAR-T cells targeting proteins like CD70, CD47, and PDL-1, which can effectively reduce tumor cells by overcoming inhibitory signaling pathways, suggesting a potential for improved cancer treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cells Targeting Immune Checkpoint Pathway Players. Golubovskaya, V.[2022]

HER2 CAR T-cell therapy shows promise for treating solid tumors, particularly in cancers like breast cancer, but it carries significant risks of severe side effects, such as cytokine release syndrome due to targeting HER2 on non-cancerous tissues.

The review highlights ongoing efforts to enhance the safety of HER2 CAR therapies through novel designs and alternative CAR host selections, aiming to minimize the risk of toxicities while maintaining therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Driving better and safer HER2-specific CARs for cancer therapy. Liu, X., Zhang, N., Shi, H.[2019]

CAR-T cell therapy has shown effectiveness in treating CD19-positive blood cancers, indicating its potential as a promising treatment option for aggressive tumors that have not responded well to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Prospective in CAR T-Based Therapy for Solid and Hematological Malignancies. Marei, HE., Cenciarelli, C.[2023]

CAR T cell therapy has shown remarkable success in treating blood cancers, but challenges remain in effectively targeting solid tumors and certain blood malignancies.

Recent advancements in genetic engineering and the use of combination agents are being explored to enhance the efficacy of CAR T cell therapy, indicating a promising direction for improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Making Potent CAR T Cells Using Genetic Engineering and Synergistic Agents. Park, CH.[2023]

Citations

1. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-01818

Genetically Engineered Cells (EGFRt/19-28z/IL-12 CAR T ... The researchers think that IL-12 may improve the effectiveness of the modified T cells, and it may also strengthen the immune system to fight cancer. Giving ...

2. healthtree.org healthtree.org/dlbcl/community/articles/armored-cart-cells-clinical-trial

New Clinical Trial with Armored CAR T-cells The investigators want to find out if, when adding the gene for IL-12, the modified T-cells may fight cancer cells more effectively and improve ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8144892/

CAR-T cells: Early successes in blood cancer and challenges ... In contrast to hematological malignancies, solid tumors not only lack conventional co-stimulatory molecules, which may be expressed on malignant and normal B ...

4. nature.com nature.com/articles/s41392-025-02269-w

CAR-T cell therapy for cancer: current challenges and ... This review begins with a comprehensive overview of CAR-T cell therapy for cancer, covering the structure of CAR-T cells and the history of their clinical ...

5. cell.com cell.com/heliyon/fulltext/S2405-8440(23)08984-3

CAR-T cell therapy for hematological malignancies In conclusion, CAR-T therapies have unique specificity and has made great progress to deal with hematological malignancies as a highly effective ...

6. withpower.com withpower.com/trial/phase-1-lymphoma-3-2024-3718c

CAR T Cells for Blood Cancers · Info for Participants Giving EGFRt/19-28z/IL-12 CAR T cells may be safe and tolerable in treating patients with relapsed or refractory CD19+ hematologic malignancies. Show more.

7. physicianresources.roswellpark.org physicianresources.roswellpark.org/news/exclusive-to-roswell-park-armored-car-clinical-trial-targets-cd19-hematologic-malignancies

Exclusive to Roswell Park, 'Armored CAR' Clinical Trial ... A phase 1 clinical trial underway exclusively at Roswell Park Comprehensive Cancer Center will evaluate a novel chimeric antigen receptor (CAR) T-cell therapy.