What side effects are associated with this type of intervention?

The most common treatments for Non-Hodgkin's Lymphoma (NHL), particularly those involving CAR-T cell therapies like CAR20.19.22 T-cells, can have several side effects. These include cytokine release syndrome (CRS), which can cause fever, nausea, headache, rapid heartbeat, low blood pressure, and difficulty breathing. Neurological toxicities are also common, manifesting as confusion, seizures, or encephalopathy. Other side effects may include infections due to immunosuppression, cytopenias (low blood cell counts), and organ toxicities such as liver or kidney dysfunction. It is crucial for patients to discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

The FDA has approved several CAR T-cell therapies for the treatment of Non-Hodgkin's Lymphoma (NHL), particularly those targeting CD19. Notable examples include axicabtagene ciloleucel (Yescarta) and tisagenlecleucel (Kymriah), both of which are engineered to target the CD19 antigen on B-cells. Additionally, brexucabtagene autoleucel (Tecartus) has been approved for mantle cell lymphoma, another subtype of NHL. These therapies have shown significant efficacy in relapsed or refractory cases. While specific FDA approvals for CAR T-cells targeting CD20 and CD22 in NHL are not mentioned, these antigens are common targets in ongoing research and clinical trials, including the CAR20.19.22 T-cells being studied.

What other types of research exist?

Promising alternatives to CAR20.19.22 T-cells for NHL patients include: 1) Nonmyeloablative or reduced-intensity hematopoietic cell transplantation (HCT), which has shown high response rates and long-term survival benefits. 2) Immunotherapies such as immune checkpoint inhibitors (e.g., anti-PD-1 or anti-PD-L1 therapies) which have demonstrated efficacy in various cancers and are being explored in NHL. 3) Other CAR-T cell therapies like Axicabtagene Ciloleucel and Tisagenlecleucel, which have shown success in relapsed or refractory large B-cell lymphoma.

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CAR T-cell Therapy

CAR T-Cell Therapy for Non-Hodgkin's Lymphoma/Chronic Lymphocytic Leukemia

Phase 1

Waitlist Available

Led By Nirav Shah, MD

Research Sponsored by Medical College of Wisconsin

Eligibility Criteria Checklist

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

Must have

Diagnosis of CLL or B-cell NHL including follicular lymphoma, marginal zone lymphoma (splenic, nodal, extranodal), mantle cell lymphoma, Burkitt lymphoma, and DLBCL with associated subtypes (high-grade or aggressive B-cell lymphoma, T-cell/histocyte rich B-cell lymphoma, primary mediastinal B-cell lymphoma, Epstein-Barr virus (EBV) + diffuse large B-cell lymphoma, transformed lymphoma such as transformed follicular or marginal zone, and Richter's transformation)

Patients must be aged ≥18 years to 80 years with relapsed or refractory B-cell non-Hodgkin Lymphoma or chronic lymphocytic leukemia

Must not have

Confirmed active human immunodeficiency virus (HIV), Hepatitis B or C infection

Patients post solid organ transplant who develop high grade lymphomas or leukemias

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 28 days after infusion

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing the safety of CAR20.19.22 T-cells in adults with B-cell non-Hodgkin lymphoma or chronic lymphocytic leukemia that haven't responded to other treatments. These special immune cells are modified to better recognize and attack cancer cells. The goal is to see if this new approach can help treat these difficult cases. CAR T-cell therapy has shown significant promise in treating B-cell malignancies, including non-Hodgkin lymphoma and chronic lymphocytic leukemia, by targeting specific antigens like CD19.

Who is the study for?

Adults aged 18-80 with relapsed or refractory B-cell malignancies like CLL or NHL, who have adequate organ function and no active CNS involvement. They must not be pregnant, agree to use double barrier contraception, and cannot participate in other clinical trials. Excluded are those with recent transplants, certain treatments within specific timeframes before the trial starts, uncontrolled autoimmune diseases requiring steroids, active infections (HIV/Hepatitis), or prior CAR T-cell therapy.

What is being tested?

The safety of different doses of CAR20.19.22 T-cells is being tested on patients with various types of B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia. This phase I study will determine the maximum tolerated dose for further research.

What are the potential side effects?

Potential side effects may include immune system reactions leading to inflammation in different organs, infusion-related reactions similar to allergic responses when cells are administered, fatigue from treatment burden on the body's resources, possible blood disorders due to bone marrow impact by the therapy.

Eligibility Criteria

Inclusion Criteria

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

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I have been diagnosed with a specific type of blood cancer.

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I am between 18 and 80 years old with a specific type of lymphoma or leukemia that has not responded to treatment.

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I am able to care for myself but may not be able to do active work.

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My kidney function is good, with proper creatinine levels and clearance.

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My liver tests are within normal limits.

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My heart and lungs are working well enough for the trial.

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My CLL has not responded to specific treatments and is still measurable.

Exclusion Criteria

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

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I have an active HIV, Hepatitis B, or C infection.

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I developed a severe form of lymphoma or leukemia after an organ transplant.

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I do not agree to participate in long-term follow-up.

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My cancer has spread to my brain or spinal cord.

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I have not had a stem cell transplant in the last 100 days, do not have GVHD, and am not on immunosuppression.

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I do not have any active cancer except for skin cancer.

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I have a serious autoimmune disease or need high doses of steroids to control it.

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I haven't had chemotherapy or antibody treatments in the last 14 days.

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I had CAR T-cell therapy over 90 days ago with a biopsy showing CD19 or CD20 expression of ≥20%.

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I haven't had chemotherapy or antibody treatments in the last 14 days.

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I am not currently using experimental drugs or enrolled in another treatment study.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 28 days after infusion

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~28 days after infusion

This trial's timeline: 3 weeks for screening, Varies for treatment, and 28 days after 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

Number of Non-hematologic Adverse Events after Infusion

Number of grade 3-4 cytokine release syndrome (CRS).

Number of grade 3-4 immune effector cell-associated neurotoxicity syndrome (ICANS)

Awards & Highlights

No Placebo-Only Group

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

Trial Design

10Treatment groups

Experimental Treatment

Group I: Indolent B-cell NHL Dose Level 1: 5x10^6 cells/kg: CAR20.19.22Experimental Treatment1 Intervention

The investigators will start at a dose of 2.5x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Group II: Indolent B-cell NHL Dose Level 0: 2.5x10^6 cells/kg: CAR20.19.22Experimental Treatment1 Intervention

The investigators will start at a dose of 2.5x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Group III: Indolent B-cell NHL Dose Level -2: 0.75x10^6 cells/kg: CAR20.19.22Experimental Treatment1 Intervention

The investigators will start at a dose of 2.5x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Group IV: Indolent B-cell NHL Dose Level -1: 1x10^6 cells/kg: CAR20.19.22Experimental Treatment1 Intervention

The investigators will start at a dose of 2.5x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Group V: Indolent B-cell NHL Dose Expansion: CAR20.19.22Experimental Treatment1 Intervention

The maximum tolerated dose intervention will be updated when it is determined. It will be one of four doses: 0.75x10\^6 cells/kg, 1x10\^6 cells/kg, 2.5x10\^6 cells/kg or 5x10\^6 cells/kg.

Group VI: Aggressive B-cell NHL Dose Level 2: 5x10^6 cells/kg: CAR20.19.22Experimental Treatment1 Intervention

The investigators will start at a dose of 1.0x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Group VII: Aggressive B-cell NHL Dose Level 1: 2.5x10^6 cells/kg: CAR20.19.22Experimental Treatment1 Intervention

The investigators will start at a dose of 1x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Group VIII: Aggressive B-cell NHL Dose Level 0: 1x10^6 cells/kg: CAR20.19.22Experimental Treatment1 Intervention

The investigators will start at a dose of 1x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Group IX: Aggressive B-cell NHL Dose Level -1: .75x10^6 cells/kg: CAR20.19.22Experimental Treatment1 Intervention

The investigators will start at a dose of 1x10\^6 cells/kg and either escalate or de-escalate based on the presence of toxicities.

Group X: Aggressive B-cell NHL Dose Expansion: CAR20.19.22Experimental Treatment1 Intervention

The maximum tolerated dose intervention will be updated when it is determined. It will be one of four doses: 0.75x10\^6 cells/kg, 1x10\^6 cells/kg, 2.5x10\^6 cells/kg or 5x10\^6 cells/kg.

0 / 18Eligibility 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

The most common treatments for Non-Hodgkin's Lymphoma (NHL) include CAR-T cell therapy, monoclonal antibodies, and chemotherapy. CAR-T cell therapy involves genetically engineering a patient's T-cells to express chimeric antigen receptors (CARs) that specifically target antigens such as CD20, CD19, and CD22 on cancer cells, leading to direct tumor cell killing. Monoclonal antibodies, like rituximab, target specific antigens on the surface of lymphoma cells, marking them for destruction by the immune system. Chemotherapy uses cytotoxic drugs to kill rapidly dividing cells, including cancer cells. These mechanisms are crucial for NHL patients as they offer targeted and effective ways to eliminate cancer cells, potentially leading to better outcomes and fewer side effects compared to traditional therapies.