CAR T-cell Therapy for Lymphoma and Leukemia

Recruiting at 1 trial location

Overseen By The Ohio State University Comprehensive Cancer Center

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Sumithira Vasu

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Active CNS involvement, Active malignancy, Uncontrolled illness, Pregnancy, others

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

Compensation: Varies

Number of Visits: 3

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test a new treatment using modified white blood cells, known as CAR T-cells, to combat certain difficult-to-treat blood cancers. The treatment targets cancers that have returned or do not respond to existing treatments, such as certain lymphomas and leukemias. Participants will first receive chemotherapy, including drugs like Cyclophosphamide and Fludarabine Phosphate, to prepare their bodies, followed by an infusion of these specially engineered CAR T-cells. This trial may suit individuals who have undergone at least two prior treatments for these cancers without success. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that special cells called anti-CD19/CD20/CD22 CAR T-cells are under investigation for their cancer-fighting abilities. Previous studies found that these cells can successfully target and destroy cancer cells in lab tests and animal studies, offering hope for treatment outcomes. However, researchers are still testing the safety of this treatment in humans.

In current studies, researchers closely monitor how patients respond to these CAR T-cells, checking for any side effects or negative reactions. Since this is an early stage of testing, the treatment's safety remains uncertain. Early trials typically focus on understanding the treatment's safety and potential side effects.

Participants in the trial might experience side effects from both the chemotherapy drugs (cyclophosphamide and fludarabine) used to prepare the body and the CAR T-cell therapy itself. Common side effects from CAR T-cell therapies include fever, tiredness, and low blood cell counts, among others. Participants should discuss potential risks with the study team.

This trial aims to learn more about the treatment's safety and effectiveness in humans, a crucial step before considering it for wider use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lymphoma and leukemia?

Researchers are excited about these CAR T-cell therapies because they offer a new way to combat lymphoma and leukemia. Unlike standard treatments like chemotherapy and radiation, which target rapidly dividing cells, these therapies use engineered T-cells that are customized to recognize and attack specific proteins (CD19, CD20, and CD22) on cancer cells. This targeted approach aims to be more precise, potentially leading to fewer side effects and greater effectiveness. Additionally, CAR T-cell therapy is known for its potential to provide long-lasting remission, setting it apart from conventional treatments.

What evidence suggests that this trial's treatments could be effective for lymphoid malignancies?

Research has shown that special immune cells, called anti-CD19/CD20/CD22 CAR T-cells, could effectively treat certain blood cancers. In lab studies, these engineered cells have successfully killed cancer cells, even when the cancer cells displayed different surface proteins. These CAR T-cells also eliminated leukemia and lymphoma tumors in animal tests. Early findings suggest that these cells can attack cancer cells that have changed to evade treatment, a common survival tactic of cancer. This trial will evaluate the effectiveness of anti-CD19/CD20/CD22 CAR T-cells in different cohorts, each receiving a lymphodepletive regimen followed by CAR T-cell therapy. This approach suggests that these CAR T-cells might treat cancers unresponsive to other treatments. ^{1 2 5 6 7}

Who Is on the Research Team?

Sumithira Vasu, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Anti-CD19/CD20/CD22 CAR T-Cells
• Cyclophosphamide
• Fludarabine Phosphate

Trial Overview The 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.

How Is the Trial Designed?

Group I: Cohort C (lymphodepletion, anti-CD19/CD20/CD22 CAR-T cells) Experimental Treatment 9 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 Treatment 9 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 Treatment 9 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.

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+

Published Research Related to This Trial

The CD22/CD19 dual-targeting CAR-T-cell therapy showed a remarkable overall response rate of 97% and a complete remission rate of 93% in patients with relapsed/refractory acute lymphoblastic leukemia (ALL), based on a meta-analysis of 14 studies involving 405 patients.

For non-Hodgkin lymphoma (NHL), the therapy resulted in an overall response rate of 85% and a complete remission rate of 57%, with manageable side effects such as cytokine release syndrome occurring in 86% of patients, indicating both efficacy and tolerability of this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Nguyen, TT., Thanh Nhu, N., Chen, CL., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas. Atar, D., Mast, AS., Scheuermann, S., et al.[2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering Novel CD19/CD22 Dual-Target CAR-T Cells for Improved Anti-Tumor Activity. Zeng, W., Zhang, Q., Zhu, Y., et al.[2022]

In a study of 16 patients with relapsed/refractory aggressive B-cell lymphoma, bispecific CAR T cells targeting both CD19 and CD22 showed a high efficacy, with 87.5% achieving an objective response and 62.5% achieving complete response.

The treatment demonstrated a favorable safety profile, with only one patient experiencing severe cytokine-release syndrome, and no cases of neurotoxicity, suggesting that this dual-targeted approach may be a safe and effective option for lymphoma therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19/CD22 Dual-Targeted CAR T-cell Therapy for Relapsed/Refractory Aggressive B-cell Lymphoma: A Safety and Efficacy Study. Wei, G., Zhang, Y., Zhao, H., et al.[2022]

In a phase 1 trial involving 15 pediatric and young adult patients with relapsed or refractory B-ALL, the dual-targeting CAR T-cell therapy AUTO3 demonstrated a favorable safety profile with no severe toxicities reported and an impressive remission rate of 86% one month post-treatment.

Despite the high initial remission rate, the one-year overall survival rate was 60% and event-free survival rate was 32%, indicating that improvements in the persistence of AUTO3 CAR T-cells are necessary to enhance long-term outcomes and prevent relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Cordoba, S., Onuoha, S., Thomas, S., et al.[2022]

CD22-targeting CAR T-cell therapies show high complete response rates, with 68% in acute lymphoblastic leukemia (ALL) and 64% in non-Hodgkin's lymphoma (NHL), indicating their efficacy in treating these malignancies.

The incidence of severe side effects, such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), is low, suggesting that these therapies are relatively safe, especially with dual-targeting CAR T-cells not increasing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review and meta-analysis of CD22 CAR T-cells alone or in combination with CD19 CAR T-cells. Fergusson, NJ., Adeel, K., Kekre, N., et al.[2023]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Loop CD20/CD19 CAR-T cells eradicate B-cell malignancies efficiently. Chen, Z., Liu, Y., Chen, N., et al.[2023]

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]

The anti-CD20-CD19 bispecific CAR T cells show promising efficacy in treating leukemia by effectively targeting and killing leukemic cells that express either CD19 or CD20, potentially reducing the risk of relapse due to antigen-loss.

In preclinical models, these bispecific CAR T cells successfully cleared leukemia cells from the blood and bone marrow, demonstrating superior anti-leukemic activity compared to traditional anti-CD20 CAR T cells, which left some leukemic cells untreated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD20-CD19 Bispecific CAR T Cells for the Treatment of B-Cell Malignancies. Martyniszyn, A., Krahl, AC., André, MC., et al.[2018]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33762438/

Trispecific CD19-CD20-CD22-targeting duoCAR-T cells ... We identified four optimal binder and signaling combinations that potently rejected xenografted leukemia and lymphoma tumors in vivo. Moreover, ...

2. science.org science.org/doi/10.1126/scitranslmed.abc6401

Trispecific CD19-CD20-CD22–targeting duoCAR-T cells ... The authors showed that trispecific duoCAR-T cells effectively killed antigen-heterogeneous mixtures of tumor cells in vitro.

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3448/529607/Phase-1-Study-of-Trispecific-Anti-CD20-Anti-CD19

Phase 1 Study of Trispecific Anti-CD20, Anti-CD19, Anti-CD22 ... In this first-in-human study using a novel CAR construct with ICOS signaling and trispecific targeting of CD19, CD20 and CD22, there was no CAR ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0006497124099531

Developing and Characterizing the Anti-Tumor Efficacy of a ... Our results demonstrate the feasibility of engineering tri-specific CAR T cells and their strong capabilities in eradicating both wild-type and antigen-loss ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07168486

Study Details | NCT07168486 | CD19.20.22 CAR T-cells ... The goal of this study is to treat patients diagnosed with relapsed or refractory positive B cell lymphoma - positive for 2 or more target ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06879340

Evaluating the Safety and Efficacy of DuoCAR20.19.22- ... This multicenter phase 1 trial with "3 + 3" dose escalation design seeks to examine the feasibility and safety of the administration of autologous T cells ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2473952924007006

Dual-targeting CAR T cells for B-cell acute lymphoblastic ... One of the main strategies to avoid CD19-negative relapse has been the development of dual CAR T cells targeting CD19 and an additional target, ...