What side effects are associated with this type of intervention?

Common treatments for B-Cell Leukemia, particularly CAR-T cell therapies like TRICAR-ALL, often involve significant side effects. These can include cytokine release syndrome (CRS), which manifests as fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and trouble breathing. Neurological toxicities are also common, presenting as confusion, delirium, seizures, or encephalopathy. Other side effects may include cytopenias (low blood cell counts), infections, and fatigue. The addition of the 4-1BB co-stimulatory molecule can enhance the persistence and efficacy of CAR-T cells but does not significantly alter the side effect profile.

What prior FDA approvals exist?

The FDA has approved several CAR-T cell therapies for the treatment of B-Cell Leukemia, particularly those targeting CD19. Notable examples include tisagenlecleucel (Kymriah) and axicabtagene ciloleucel (Yescarta), both of which are CD19-directed CAR-T cell therapies. These treatments have shown significant efficacy in relapsed or refractory B-cell malignancies. While there are no FDA-approved CAR-T therapies specifically targeting CD20 and CD22 in combination with CD19 and the 4-1BB co-stimulatory molecule, ongoing research and clinical trials, such as the TRICAR-ALL study, are exploring these multi-targeted approaches to enhance treatment outcomes.

What other types of research exist?

Promising alternatives to TRICAR-ALL T cells for B-Cell Leukemia patients include: 1) Anti-BCMA CAR T-Cell Therapy (e.g., idecabtagene vicleucel, ciltacabtagene autoleucel) which targets B-cell maturation antigen (BCMA) and has shown efficacy in multiple myeloma. 2) Bispecific T cell engagers (BiTEs) such as teclistamab (targeting BCMA and CD3) and AMG 701. 3) Antibody-drug conjugates like belantamab mafodotin, which targets BCMA. These therapies offer novel mechanisms and have demonstrated promising results in clinical studies.

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CAR T-cell Therapy

CAR-T Cell Therapy for B-Cell Leukemia (TRICAR-ALL Trial)

Phase 1

Recruiting

Led By Bahey Salem, MD

Research Sponsored by Baylor College of Medicine

Eligibility Criteria Checklist

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

Must have

Projected age ≥ 12 months and ≤ 21 years at the time of TRICAR-ALL T cell infusion (first three patients enrolled on dose level 1 will be 12 years and older)

Diagnosis of refractory or recurrent B cell Acute Lymphoblastic Leukemia (B-ALL) with expression of CD19, CD20 and/or CD22

Must not have

Active malignancy other than disease under study

History of symptomatic CNS pathology or ongoing symptomatic CNS pathology requiring medical intervention

Timeline

Screening 3 weeks

Treatment Varies

Follow Up within 28 days of the tricar-all t cell infusion.

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment for patients with a type of blood cancer called Acute Lymphoblastic Leukemia (ALL) that hasn't responded to other treatments. The treatment uses the patient's own T cells, which are modified in the lab to better fight cancer. These enhanced T cells are then reintroduced into the patient's body to target and kill cancer cells more effectively. This therapy has shown promise in treating relapsed or refractory acute lymphoblastic leukemia (ALL).

Who is the study for?

This trial is for young people aged 12 months to 21 years with B cell Acute Lymphoblastic Leukemia that's resistant or has returned. They must weigh at least 10 kg, have certain levels of liver and kidney function, a good heart function score, and be expected to live more than 8 weeks. Those who can get pregnant must agree to use effective birth control during the study.

What is being tested?

The trial tests 'TRICAR-ALL' T-cells combined with lymphodepletion chemotherapy in patients with leukemia. These special T-cells are engineered in the lab to target cancer cells more effectively by using a modified antibody that sticks to three specific proteins on leukemia cells.

What are the potential side effects?

Possible side effects include reactions related to immune system activation such as fever, fatigue, difficulty breathing, changes in blood pressure, and organ inflammation. There may also be risks associated with the chemotherapy used before receiving the CAR-T cells.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 12 and 21 years old and eligible for the TRICAR-ALL T cell infusion.

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My leukemia is not responding to treatment and has markers CD19, CD20, or CD22.

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I weigh at least 10 kg.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have any cancer other than the one being studied.

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I have a brain condition that needs treatment.

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I do not have any severe infections, active viral infections, or immune deficiencies.

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I have had a bone marrow transplant and am not currently experiencing active GVHD or taking immunosuppressants.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ within 28 days of the tricar-all t cell infusion.

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~within 28 days of the tricar-all t cell infusion.

This trial's timeline: 3 weeks for screening, Varies for treatment, and within 28 days of the tricar-all t cell infusion. for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Dose-limiting toxicity (DLT) rate by CTCAE v5.0

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: Autologous TRICAR-ALL T-Cells and lymphodepletion chemotherapyExperimental Treatment1 Intervention

Three dose levels will be evaluated. The TRICAR-ALL T-cells will be administered after lymphodepletion chemotherapy with Cyclophosphamide and fludarabine.

0 / 7Eligibility criteria met

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

CAR-T cell therapies for B-Cell Leukemia involve modifying a patient's T cells to express chimeric antigen receptors (CARs) that specifically target antigens such as CD19, CD20, and CD22 on the surface of leukemia cells. These CARs enable the T cells to recognize and kill the cancerous B cells. The addition of a co-stimulatory molecule like 4-1BB enhances the proliferation and persistence of these CAR-T cells, improving their efficacy. This targeted approach is significant for B-Cell Leukemia patients as it offers a personalized and potent treatment option, often leading to durable remissions in cases where traditional therapies have failed.

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.