36 Participants Needed

CAR-T Cells for Non-Hodgkin's Lymphoma

JM
LB
Overseen ByLaurel Brechtel
Age: 18+
Sex: Any
Trial Phase: Phase 1
Sponsor: C. Babis Andreadis
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This study will assess safety and feasibility of infusing genetically modified autologous T cells transduced to express a chimeric antigen receptor targeting the B cell surface antigen Cluster of Differentiation 19 (CD19)

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use corticosteroids within 7 days before the infusion, except for preventing nausea during chemotherapy.

What data supports the effectiveness of the treatment for Non-Hodgkin's Lymphoma?

Research shows that CD19-directed CAR T-cell therapy is effective for patients with relapsed or hard-to-treat B-cell non-Hodgkin lymphoma, with encouraging response rates observed in various studies.12345

Is CAR-T cell therapy safe for humans?

CAR-T cell therapy, including anti-CD19 CAR-T cells, has been shown to be effective but can have side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). These side effects are generally manageable with proper medical care, but ongoing research is needed to better understand and reduce these risks.678910

How does the treatment with anti-CD19 CAR-T cells differ from other treatments for non-Hodgkin's lymphoma?

Anti-CD19 CAR-T cell therapy is unique because it uses the patient's own immune cells, which are modified to specifically target and destroy cancer cells in non-Hodgkin's lymphoma. This approach is different from traditional treatments like chemotherapy, as it harnesses the body's immune system to fight the cancer.411121314

Research Team

CB

C. Babis Andreadis, MD

Principal Investigator

University of California, San Francisco

Eligibility Criteria

Adults with certain types of B-cell Non-Hodgkin Lymphoma that have relapsed or didn't respond to previous treatments can join. They should not be eligible for stem cell transplant, must have tried at least two systemic therapies, and still show CD19 positive cells. Key organ functions need to be within normal ranges, they shouldn't have other active cancers or severe illnesses, and women who can get pregnant must agree to use contraception for a year after treatment.

Inclusion Criteria

My lymphoma shows up on PET scans.
My B-cell NHL subtype fits the specific treatment history criteria.
I am not pregnant and agree to use birth control for a year after treatment.
See 4 more

Exclusion Criteria

Specific criteria for eligibility for infusion of investigational product
I am HIV positive.
Pregnancy or breastfeeding
See 8 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and CAR-T Cell Manufacturing

Participants undergo apheresis for collection of autologous peripheral blood mononuclear cells, followed by CAR-T cell manufacturing

Approximately 13-14 days
1 visit (in-person) for apheresis

Lymphodepleting Chemotherapy

Participants receive 3 days of immunosuppressive chemotherapy with cyclophosphamide and fludarabine

3 days

CAR-T Cell Infusion

Participants receive a single infusion of anti-CD19 CAR-T cells

1 day
1 visit (in-person)

Follow-up

Participants are monitored for safety, disease status, and survival

12 months

Long-term Follow-up

Participants are followed for long-term safety and survival

Up to 15 years

Treatment Details

Interventions

  • anti-CD19 CAR-T cells
  • Cyclophosphamide
  • Fludarabine
Trial OverviewThe trial is testing genetically modified T cells that target CD19 on the surface of B cells. Patients will receive Cyclophosphamide and Fludarabine as part of the preparation before getting these anti-CD19 CAR-T cells infused into their bloodstream.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment RegimenExperimental Treatment3 Interventions
Apheresis (1 day): Autologous lymphocytes/ mononuclear cell collection will be collected through standard apheresis procedures as per University of California, San Francisco (UCSF) institutional practices CAR-T cell manufacturing (estimated \~13-14 days) Lymphodepleting chemotherapy: 3 days of immunosuppressive chemotherapy. Cyclophosphamide given at a dose of 300 mg/m2/IV and fludarabine given at 30 mg/m2 /IV on days -5, -4, and -3. CAR-T cell infusion (1 day): The infusion of CAR-T cells targeting CD19 will occur over 5-30 minutes.

Find a Clinic Near You

Who Is Running the Clinical Trial?

C. Babis Andreadis

Lead Sponsor

Trials
5
Recruited
130+

University of California, Davis

Collaborator

Trials
958
Recruited
4,816,000+

Findings from Research

CD19-directed CAR T-cell therapy has shown promising results in treating relapsed/refractory B-cell non-Hodgkin lymphoma, with 30-40% of patients achieving durable responses in pivotal phase I/II trials, leading to FDA and EMA approvals for specific therapies.
Despite its effectiveness, the therapy is associated with significant toxicities, such as cytokine release syndrome and neurotoxicity, which can limit its use and present challenges in patient management during treatment.
CD19-directed CAR T-cell therapy in B-cell NHL.Kersten, MJ., Spanjaart, AM., Thieblemont, C.[2021]
CAR.λ T cells effectively target and kill Igλ+ lymphoma cells and chronic lymphocytic leukemia (CLL) cells, showing similar antitumor activity to the established CAR.CD19 T cells in both laboratory and animal models.
Importantly, CAR.λ and CAR.κ T cells selectively deplete only the corresponding light chain-expressing normal B cells, preserving the other type, which suggests a safer approach with minimal impact on the immune system's ability to produce antibodies.
CAR T cells Targeting Human Immunoglobulin Light Chains Eradicate Mature B-cell Malignancies While Sparing a Subset of Normal B Cells.Ranganathan, R., Shou, P., Ahn, S., et al.[2022]
CD19CAR T cells have shown promising results in treating aggressive B-lineage cancers, but their effectiveness can be limited by the loss of the targeted CD19 antigen, leading to treatment failure.
The newly developed adapter CAR T cell technology (AdCAR) allows for multitargeting of different antigens, such as CD20 and CD22, which can enhance the anti-cancer activity and potentially overcome issues related to antigen loss in lymphoma treatments.
Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas.Atar, D., Mast, AS., Scheuermann, S., et al.[2022]

References

CD19-directed CAR T-cell therapy in B-cell NHL. [2021]
CAR T cells Targeting Human Immunoglobulin Light Chains Eradicate Mature B-cell Malignancies While Sparing a Subset of Normal B Cells. [2022]
Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas. [2022]
Immunotherapy with cells. [2023]
Anti-CD19 Chimeric Antigen Receptor T Cell Therapies: Harnessing the Power of the Immune System to Fight Diffuse Large B Cell Lymphoma. [2020]
Anti-CD19 chimeric antigen receptor-modified T cells for B-cell malignancies: a systematic review of efficacy and safety in clinical trials. [2022]
Efficacy and safety of CD19 chimeric antigen receptor T cells in the treatment of 11 patients with relapsed/refractory B-cell lymphoma: a single-center study. [2022]
CAR-T Cell Therapy in Diffuse Large B Cell Lymphoma: Hype and Hope. [2020]
Complications after CD19+ CAR T-Cell Therapy. [2020]
10.United Statespubmed.ncbi.nlm.nih.gov
Recent Advances in CAR-T Cell Therapy for Non-Hodgkin Lymphoma. [2020]
Anti-CD19 chimeric antigen receptor T-cell therapy in B-cell lymphomas: current status and future directions. [2022]
12.United Statespubmed.ncbi.nlm.nih.gov
CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. [2023]
13.United Statespubmed.ncbi.nlm.nih.gov
Clinical Efficacy and Tumor Microenvironment Influence in a Dose-Escalation Study of Anti-CD19 Chimeric Antigen Receptor T Cells in Refractory B-Cell Non-Hodgkin's Lymphoma. [2020]
Anti-CD19 chimeric antigen receptor T cells secreting anti-PD-L1 single-chain variable fragment attenuate PD-L1 mediated T cell inhibition. [2022]