What side effects are associated with this type of intervention?

Common treatments for Chronic Lymphocytic Leukemia (CLL) include CAR T cell therapy, Bruton tyrosine kinase (BTK) inhibitors, BCL2 inhibitors, monoclonal antibodies, purine analogs, and alkylating agents. CAR T cell therapy, such as the Anti-CD19 Chimeric Antigen Receptor (CAR) TBI-2001, is associated with severe side effects including cytokine release syndrome, which can lead to multiorgan dysfunction and acute kidney injury, as well as neurological toxicities. BTK inhibitors like ibrutinib can cause bleeding, infections, and cardiac issues. BCL2 inhibitors such as venetoclax may lead to tumor lysis syndrome. Monoclonal antibodies, including rituximab, can result in infusion reactions and increased risk of infections. Purine analogs and alkylating agents are known for causing myelosuppression and increased infection risk.

What prior FDA approvals exist?

The FDA has approved several treatments for Chronic Lymphocytic Leukemia (CLL) that target CD19 or use CAR-T technology. Notably, anti-CD19 CAR-T therapies such as Kymriah (tisagenlecleucel) and Yescarta (axicabtagene ciloleucel) have been approved for certain types of B-cell malignancies, including CLL. These therapies involve genetically engineering a patient's T cells to target and destroy CD19+ cancer cells. Additionally, monoclonal antibodies like rituximab, ofatumumab, and obinutuzumab, which target CD20, have also been approved for CLL treatment. These therapies have shown efficacy in managing relapsed or refractory CLL, providing new options for patients who do not respond to conventional treatments.

What other types of research exist?

Promising novel alternatives to Anti-CD19 CAR TBI-2001 for CLL patients include: 1) Bispecific antibodies targeting CD3 and PSMA, which have shown PSA declines in early studies. 2) BTK inhibitors like ibrutinib, acalabrutinib, and zanubrutinib, which are effective in various CLL subtypes. 3) Venetoclax plus obinutuzumab, which has shown high rates of undetectable minimal residual disease (MRD). These therapies offer different mechanisms of action and have demonstrated efficacy in clinical trials.

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CAR T-cell Therapy

CAR-T Therapy for B-Cell Lymphoma

Phase 1

Recruiting

Led By Marcus Butler, M.D.

Research Sponsored by University Health Network, Toronto

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up one year

Awards & highlights

No Placebo-Only Group

Summary

This trial tests TBI-2001, a therapy that modifies a patient's immune cells to better attack cancer. It targets patients whose cancers have not responded to other treatments. The treatment works by enhancing the immune cells' ability to kill cancer cells.

Who is the study for?

This trial is for adults over 18 with CD19+ B-cell Lymphoma, CLL, or SLL who've had at least two prior treatments. They should be in good health with a life expectancy of more than 4 months and have not received cancer treatment within the last two weeks. Pregnant women, those with certain medical conditions or history of organ transplant requiring immunosuppression are excluded.

What is being tested?

The study tests TBI-2001 (a CAR-T therapy targeting CD19) along with Cyclophosphamide and Fludarabine in patients whose disease returned after treatment or didn't respond to previous therapies. It's an early-phase trial to check safety and effectiveness, gradually increasing doses to find the right amount.

What are the potential side effects?

Potential side effects include immune system reactions that can affect normal cells leading to symptoms like fever, fatigue, breathing difficulties; there may also be risks from chemotherapy drugs used such as nausea, hair loss, and increased infection risk.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ one year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~one year

This trial's timeline: 3 weeks for screening, Varies for treatment, and one year for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Recommended phase 2 dose (RP2D) of TBI-2001

Safety of TBI-2001

Secondary study objectives

Efficacy of TBI-2001; Durable Response Rate (DRR)

Efficacy of TBI-2001; Overall Response Rate (ORR)

Efficacy of TBI-2001; Overall survival (OS)

+1 more

Other study objectives

Minimal residual disease (MRD) negative rate (in CLL patients)

Persistence of TBI-2001

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Experimental: Dose Level 1 to 3Experimental Treatment3 Interventions

0.3 to 3 x 10\^6 autologous CD19-CAR-T cells/kg per patient will be administered intravenously after a conditioning chemotherapy with cyclophosphamide and fludarabine.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cyclophosphamide

2010

Completed Phase 4

~2310

Fludarabine

2012

Completed Phase 4

~1830

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Chronic Lymphocytic Leukemia (CLL) include Bruton tyrosine kinase (BTK) inhibitors, BCL2 inhibitors, monoclonal antibodies, and CAR T-cell therapies. BTK inhibitors, such as ibrutinib, block the BTK enzyme, which is crucial for the survival and proliferation of CLL cells. BCL2 inhibitors, like venetoclax, induce apoptosis in CLL cells by inhibiting the BCL2 protein that prevents cell death. Monoclonal antibodies, such as rituximab, target specific antigens on CLL cells, marking them for destruction by the immune system. CAR T-cell therapies, including those targeting CD19 like TBI-2001, involve genetically engineering a patient's T cells to express a receptor that recognizes and kills CD19+ CLL cells. These treatments are significant for CLL patients as they offer targeted approaches to eliminate cancer cells, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

Driving Out Chronic Lymphocytic Leukemia With CAR T Cells.Chimeric Antigen Receptor-T-Cell Therapy for B-Cell Hematological Malignancies: An Update of the Pivotal Clinical Trial Data.Immunotherapies in CLL.