UCD19 CAR T Cells for B-Cell Lymphoma

Overseen By Chanel Mansfield, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Colorado, Denver

Must not be taking: Monoclonal antibodies, Immunomodulatory drugs, Corticosteroids

Disqualifiers: Severe psychiatric illness, HIV, Hepatitis B, others

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

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial requires that you stop certain medications before participating. You must not have received monoclonal antibody therapy, immunomodulatory drugs, or corticosteroids above a certain dose within 14 days before the cell collection process. Please discuss your current medications with the study team to see if they are allowed.

What data supports the effectiveness of the treatment UCD19 CAR T Cells for B-Cell Lymphoma?

Research shows that CD19 CAR T-cell therapy is effective in treating B-cell lymphoma, with many patients experiencing significant responses, including complete and partial remissions. This treatment has been particularly successful in patients with relapsed or refractory B-cell lymphomas, where traditional therapies have failed. ^{1 2 3 4 5}

What safety data exists for UCD19 CAR T Cells in humans?

UCD19 CAR T Cells have been tested in patients with B-cell lymphoma, showing some risks like cytokine release syndrome (CRS) and neurotoxicity, which occurred in about 11% of patients. These side effects are known but can often be managed with specific treatments. ^{6 7 8 9 10}

How is the UCD19 CAR T Cells treatment different from other treatments for B-cell lymphoma?

UCD19 CAR T Cells treatment is unique because it uses modified T-cells that specifically target the CD19 protein on B-cells, offering a personalized approach for patients with aggressive B-cell lymphomas that do not respond to standard chemotherapy. This treatment has shown the potential to induce long-lasting remissions in cases previously considered incurable. ^{3 5 11 12 13}

What is the purpose of this trial?

This study will test whether immune cells modified to recognize B-cell non-Hodgkin lymphoma (NHL) can be successfully manufactured at the University of Colorado Anschutz and whether these cells can be administered with an acceptable safety profile. Adults who have been diagnosed with B-cell non-Hodgkin lymphoma (NHL) that has relapsed or no longer responds to chemotherapy (relapsed or refractory) may be eligible to participate in this study. The investigators will use participants own immune cells, called T cells, to kill the lymphoma. These T cells are involved in fighting infections and in some cases, can also kill cancer cells. The investigators will extract T cells from the participant's blood, modify the cells in a laboratory, and then return teh cells to the participant's body via intravenous (IV) injection. In the laboratory, the investigators will add a new gene into the T cells that allows the T cells to recognize and kill the lymphoma cells, and allows these modified cells to multiply and increase in numbers. To put the new gene into your T cells, the investigators will use a weakened virus. The virus is modified so that it cannot multiply or spread once the cells are infused.

Research Team

Michael Verneris, MD

Principal Investigator

University of Colorado Denver, Anschutz Medical Campus

Manali Kamdar, MD

Principal Investigator

University of Colorado Denver, Anschutz Medical Campus

Eligibility Criteria

Adults aged 18-80 with B-cell non-Hodgkin lymphoma that's come back or didn't respond to treatment may join. They must have no other cure options, be in fairly good health, and not planning pregnancy for a year post-treatment. Excluded are those with recent monoclonal antibody therapy, severe psychiatric issues, certain lung/infection conditions, prior gene/CAR T cell therapy, HIV/Hepatitis B/C infection.

Inclusion Criteria

There are no other treatments that can cure your condition, as decided by your main doctor.

You do not currently have Graft-versus-Host Disease (GvHD).

Provision of signed and dated Informed Consent form

Exclusion Criteria

You have received a type of medication called monoclonal antibody therapy within the past 14 days.

The doctor thinks that cellular therapy is not a good option for you, for any reason.

Prior therapies:

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepleting Chemotherapy

Participants receive lymphodepleting chemotherapy prior to CAR T cell infusion

Up to 1 month

CAR T Cell Infusion

Infusion of UCD19 CAR T Cells after successful manufacture and lymphodepleting chemotherapy

Day 0 (infusion)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Long Term Follow Up

Long-term safety monitoring of UCD19 CAR T Cells for latent adverse reactions

Up to 15 years

Treatment Details

Interventions

• UCD19 CAR T Cells

Trial Overview The trial is testing UCD19 CAR T Cells on adults with relapsed/refractory B-NHL. Participants' own T cells will be modified in the lab to fight cancer by adding a new gene through a weakened virus and then returned to their body via IV injection.

Participant Groups

Group I: UCD19 CAR T Cells Experimental Treatment 1 Intervention

Participants will receive lymphodepleting chemotherapy followed by infusion of UCD19 CAR T Cells (Lentiviral Vector \[LV\] Transduced Autologous Peripheral Blood Lymphocytes

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Findings from Research

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]

Anti-CD19 CAR-T cell therapy successfully achieved a complete response in a patient with relapsed/refractory follicular lymphoma, demonstrating its efficacy in treating this type of lymphoma.

The therapy not only addressed the lymphoma but also allowed for subsequent curative treatment of gastric adenocarcinoma, indicating its potential for use in patients with multiple malignancies while maintaining a good quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of a case with synchronous follicular lymphoma and gastric adenocarcinoma with CD19 CAR T cells and literature review. Liu, J., Cao, F., Li, Z., et al.[2022]

In a study involving 9 patients with refractory/relapsed B cell lymphoma, a novel anti-CD19 CAR T cell therapy showed a high overall response rate of 77.8%, with 55.6% achieving complete remission.

The treatment demonstrated a favorable safety profile, with only 11.1% of patients experiencing severe cytokine release syndrome and neurotoxicity, while some patients maintained complete remission for over 20 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. Liu, X., Zhang, Y., Li, K., et al.[2021]

In a study of 50 patients receiving CD19 CAR-T cell therapy, 36% experienced infectious complications, with a median time to infection of 225 days, indicating that infections can occur well after treatment.

Severe infections were common, with 54.8% leading to significant health issues, including hospitalization and even death in 6% of patients, highlighting the need for ongoing monitoring and improved antimicrobial prophylaxis strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. Walker, B., Zimmer, AJ., Stohs, EJ., et al.[2023]

Adoptive cellular immunotherapy using anti-CD19 CAR-T cells has significantly improved treatment outcomes for patients with relapsed or refractory B cell lymphomas, leading to durable remissions, with two products already FDA-approved and a third in large clinical trials.

Despite their effectiveness, CAR-T cell therapies can cause serious side effects like infections and cytokine release syndrome, highlighting the need for better understanding of these toxicities and strategies to mitigate them.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. Kallam, A., Vose, JM.[2020]

CD19 is a highly effective target for CAR T-cell therapies, showing significant responses in patients with relapsed B-cell malignancies, particularly chronic lymphocytic leukemia and acute lymphoblastic leukemia.

While treatment with CD19-CAR T cells can lead to severe systemic inflammatory reactions, these are generally reversible with proper medical care, highlighting the importance of monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-CAR trials. Ramos, CA., Savoldo, B., Dotti, G.[2022]

CD19-directed CAR T-cell therapy has significantly transformed the treatment approach for aggressive B-cell non-Hodgkin lymphoma, offering new hope for patients.

There are currently three commercially available CAR T-cell therapies targeting CD19, indicating a growing acceptance and application of this innovative immunotherapy in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. Gideon, J.[2023]

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

References

1. China pubmed.ncbi.nlm.nih.gov

[Efficacy and safety of CD19 chimeric antigen receptor T cells for the treatment of 22 patients with B-cell lymphoma]. [2020]

2. China pubmed.ncbi.nlm.nih.gov

A narrative review of critical factors for better efficacy of CD19 chimeric antigen receptor T cell therapy in the treatment of B cell malignancies. [2022]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Successful treatment of a case with synchronous follicular lymphoma and gastric adenocarcinoma with CD19 CAR T cells and literature review. [2022]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Clinical immunotherapy of B-cell malignancy using CD19-targeted CAR T-cells. [2019]

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

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. [2021]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Cellular Therapy Updates in B-Cell Lymphoma: The State of the CAR-T. [2021]

8. Denmark pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. [2023]

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

Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. [2020]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Benefits of Chimeric Antigen Receptor T-Cell Therapy for B-Cell Lymphoma. [2022]

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

CD19-CAR trials. [2022]

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

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. [2023]

13. Netherlands pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]