54 Participants Needed

CAR T-cell Therapy for Lymphoma and Leukemia

Recruiting at 1 trial location
TO
Overseen ByThe Ohio State University Comprehensive Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

This trial tests the safety and best dose of a new treatment using modified immune cells (CAR T-cells) for patients with certain recurring or hard-to-treat lymphoid cancers. The treatment involves giving patients a brief period of chemotherapy followed by an infusion of these specially designed cells to target and kill cancer cells. Anti-CD19 CAR T-cells currently represent transformational therapy for relapsed/refractory aggressive B-cell lymphomas where durable remissions can be induced in patients with previously incurable chemotherapy-refractory disease.

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, patients must be off immunosuppressive agents if they have had an allogeneic stem cell transplant or donor lymphocyte infusion within 2 months of the planned CAR-T cell infusion.

What data supports the effectiveness of the treatment Anti-CD19/CD20/CD22 CAR-T cells for lymphoma and leukemia?

Research shows that trispecific CAR-T cells targeting CD19, CD20, and CD22 can effectively eliminate tumors in preclinical models, even when some cancer cells lose one or more of these targets. This approach may prevent relapse by overcoming the issue of antigen loss, which is a common cause of treatment failure in traditional CAR-T therapies.12345

Is CAR T-cell therapy safe for humans?

CAR T-cell therapy, including those targeting CD19, CD20, and CD22, has shown a generally favorable safety profile in clinical trials for leukemia and lymphoma. Severe side effects like cytokine release syndrome (CRS) and neurotoxicity are rare, with most patients experiencing mild to moderate symptoms. Long-term safety data is still being gathered, but current studies suggest it is a promising and generally safe treatment option.16789

What makes the Anti-CD19/CD20/CD22 CAR-T cell treatment unique for lymphoma and leukemia?

This treatment is unique because it targets three different proteins (CD19, CD20, and CD22) on cancer cells, which helps prevent the cancer from escaping treatment by losing one of these targets. This multi-target approach is designed to reduce the risk of relapse and improve the effectiveness of the therapy compared to treatments that target only one or two proteins.123710

Research Team

Sumithira Vasu - Professor of Internal ...

Sumithira Vasu, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

Adults with certain relapsed or refractory lymphoid cancers, including non-Hodgkin lymphoma and various types of leukemia. Participants must have tried at least two prior therapies, have a minimum level of white blood cells, good heart and lung function, and agree to use highly effective contraception. Excluded are those with recent transplants, active infections or other malignancies that could affect the trial's safety.

Inclusion Criteria

My high-grade B-cell lymphoma came back within a year after my stem cell transplant.
I am 18 or older with a specific type of blood cancer, have received certain treatments, can move around, and understand the consent form.
I have CLL and have been treated with at least 2 therapies including a BTK inhibitor and venetoclax.
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Exclusion Criteria

I don't have myelodysplasia, hepatitis B, significant brain issues, recent autoimmune treatment, or recent live vaccines.
Uncontrolled intercurrent illness, HIV-seropositive patients without effective anti-retroviral therapy, pregnant or breastfeeding women
I do not have active brain or spinal cord cancer.
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Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks
1 visit (in-person)

Lymphodepletion

Patients receive cyclophosphamide and fludarabine to prepare the body before CAR T-cell therapy

4 days
Daily visits for infusion

CAR T-Cell Therapy

Patients receive anti-CD19/CD20/CD22 CAR-T cells intravenously

1-2 days
1-2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years
Regular visits on days 1-7, 14, 21, 30, 60, 90, at months 6, 24, 36, 48, and 60, then annually

Treatment Details

Interventions

  • Anti-CD19/CD20/CD22 CAR T-Cells
  • Cyclophosphamide
  • Fludarabine Phosphate
Trial OverviewThe trial is testing genetically engineered CAR T-cells targeting CD19/CD20/CD22 on cancer cells following chemotherapy (cyclophosphamide and fludarabine). It aims to determine the safest dose for infusion of these modified T-cells in patients whose cancers haven't responded well to previous treatments.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells)Experimental Treatment9 Interventions
LYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV on days -6 and -5 and fludarabine IV on days -6 to -3 in the absence of disease progression or unacceptable toxicity. CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0 and 7. Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
Group II: Cohort B (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells)Experimental Treatment9 Interventions
LYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV over 60 minutes on day -6 and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity. CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0 and 7. Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.
Group III: Cohort A (lymphodepletion; anti-CD19/CD20/CD22 CAR-T cells)Experimental Treatment9 Interventions
LYMPHODEPLETIVE REGIMEN: Patients receive cyclophosphamide IV over 60 minutes on day -6 and fludarabine IV over 30 minutes on days -5 to -3 in the absence of disease progression or unacceptable toxicity. CAR T-CELL THERAPY: Patients receive anti-CD19/CD20/CD22 CAR-T cells IV over 5-30 minutes on day 0. Patients undergo ECHO or MUGA and may undergo tissue biopsy during screening, undergo apheresis on study, and undergo bone marrow biopsy and aspiration and blood sample collection throughout the study.

Find a Clinic Near You

Who Is Running the Clinical Trial?

Sumithira Vasu

Lead Sponsor

Trials
6
Recruited
140+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

The study developed trispecific duoCAR-T cells that target three different B cell leukemia antigens (CD19, CD20, and CD22) to overcome the problem of antigen loss in patients with leukemia and lymphoma, showing promise in preventing relapse.
In mouse models, these duoCAR-T cells effectively rejected tumors composed of various B cell lymphoma variants, while traditional monoCAR-T cells targeting only one antigen failed to prevent tumor progression, highlighting the efficacy of multispecific targeting.
Trispecific CD19-CD20-CD22-targeting duoCAR-T cells eliminate antigen-heterogeneous B cell tumors in preclinical models.Schneider, D., Xiong, Y., Wu, D., et al.[2021]
Bispecific CAR-T cells targeting both CD19 and CD20 have shown the ability to eliminate lymphoma cells that are negative for either antigen, providing a promising strategy to overcome treatment failures associated with CD19 CAR-T therapy.
Among the tested CAR structures, the loop2019 CAR demonstrated superior efficacy in eradicating lymphoma cell lines and primary cells from patients at very low doses, significantly prolonging survival in a mouse model, indicating its potential for clinical application.
Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently.Chen, Z., Liu, Y., Chen, N., et al.[2023]
BiCAR-T cells, which target both CD19 and CD22, demonstrated significant anti-tumor effects in both laboratory and animal models, suggesting enhanced efficacy compared to single-target CAR-T therapies.
This dual targeting approach may help prevent relapse in B-cell acute lymphoblastic leukemia (B-ALL) by reducing the risk of immune escape due to loss of the targeted antigens.
Engineering Novel CD19/CD22 Dual-Target CAR-T Cells for Improved Anti-Tumor Activity.Zeng, W., Zhang, Q., Zhu, Y., et al.[2022]

References

Trispecific CD19-CD20-CD22-targeting duoCAR-T cells eliminate antigen-heterogeneous B cell tumors in preclinical models. [2021]
Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently. [2023]
Engineering Novel CD19/CD22 Dual-Target CAR-T Cells for Improved Anti-Tumor Activity. [2022]
Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas. [2022]
CD20-CD19 Bispecific CAR T Cells for the Treatment of B-Cell Malignancies. [2018]
A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells. [2023]
Effectiveness and safety of CD22 and CD19 dual-targeting chimeric antigen receptor T-cell therapy in patients with relapsed or refractory B-cell malignancies: A meta-analysis. [2023]
CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. [2022]
CD19/CD22 Dual-Targeted CAR T-cell Therapy for Relapsed/Refractory Aggressive B-cell Lymphoma: A Safety and Efficacy Study. [2022]
10.United Statespubmed.ncbi.nlm.nih.gov
Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. [2021]