What side effects are associated with this type of intervention?

Common side effects of CAR T-cell therapies, such as those targeting CD30 with CCR4 for enhanced tumor localization, include cytokine release syndrome (CRS) with symptoms like fever, nausea, headache, rash, rapid heartbeat, low blood pressure, and difficulty breathing. Neurotoxicity, presenting as confusion, seizures, and severe headaches, is also significant. Other side effects include cytopenias (low blood cell counts), infections, and fatigue. These side effects vary in severity and necessitate careful monitoring and management.

What prior FDA approvals exist?

The FDA has approved several CAR T-cell therapies for immunoproliferative disorders. Notably, brexucabtagene autoleucel (formerly KTE-X19) is a CAR T-cell therapy targeting CD19, approved for relapsed or refractory mantle cell lymphoma. This therapy has shown durable remissions but comes with significant toxicity risks. While specific FDA approvals for CAR T-cell therapies targeting CD30 with CCR4 for enhanced tumor localization, like ATLCAR.CD30.CCR4, are not mentioned, the approval of similar CAR T-cell therapies indicates a promising direction for such treatments.

What other types of research exist?

Promising novel alternatives to ATLCAR.CD30.CCR4 for immunoproliferative disorders include: 1) GD2-CAR T cell therapy, which targets H3K27M-mutated diffuse midline gliomas and has shown potential in treating other cancers. 2) ONC201, a selective DRD2 antagonist, which has demonstrated efficacy in treating H3 K27M-mutant diffuse midline gliomas. 3) Anti-BCMA CAR T-cell therapy (bb2121) for relapsed or refractory multiple myeloma, which has shown significant clinical responses. 4) Teclistamab, a bispecific antibody targeting BCMA, which redirects T cells to attack multiple myeloma cells. These therapies represent cutting-edge approaches in the field of immunotherapy for cancer treatment.

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CAR T-cell Therapy

CAR-T Cell Therapy for Lymphoma

Phase 1

Recruiting

Led By Natalie Grover, MD

Research Sponsored by UNC Lineberger Comprehensive Cancer Center

Eligibility Criteria Checklist

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

Must have

Karnofsky score of > 60%

Be older than 18 years old

Must not have

Has a known additional malignancy that is active and/or progressive requiring treatment

Active infection with HIV, HTLV, HCV

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 15 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new treatment using lab-modified immune cells to target and kill cancer cells in patients with certain types of lymphoma that haven't responded to other treatments. The modified cells are designed to better locate and destroy cancer cells. This new approach extends the capacity of the patient's own immune cells to detect and eliminate cancer cells.

Who is the study for?

This trial is for adults over 18 with certain types of lymphoma, like Mycosis fungoides or Sezary syndrome, that have not improved after at least two treatments. Participants must have CD30+ disease and adequate organ function. They cannot be on strong CYP1A2 inhibitors, have uncontrolled infections, or be pregnant. Those with HIV, HTLV, HCV or active hepatitis B are excluded.

What is being tested?

The study tests new cancer treatments using T cells genetically modified to target CD30+ lymphoma cells. One group receives ATLCAR.CD30.CCR4 cells designed to navigate towards tumors; another gets these plus additional ATLCAR.CD30 cells. The goal is to find the safest dose for these therapies.

What are the potential side effects?

Potential side effects may include immune reactions due to the engineered T-cells targeting healthy tissue by mistake (autoimmunity), infusion-related reactions from the cell therapy administration process, and typical chemotherapy-associated risks such as fatigue and increased infection susceptibility.

Eligibility Criteria

Inclusion Criteria

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

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

Exclusion Criteria

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

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I have another cancer that is growing and needs treatment.

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I do not have an active HIV, HTLV, or HCV infection.

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I do not have any ongoing serious infections.

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My tumor is located where it could block my airways if it grows.

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I am currently taking 10mg or more of prednisone daily or its equivalent.

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I am currently infected with hepatitis B.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 15 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~15 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 15 years 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 participants with adverse events (AE) as a measure of safety and tolerability ATLCAR.CD30.CCR4 and ATLCAR.CD30 cells

Secondary study objectives

Differential infiltration of ATLCAR.CD30.CCR4 vs. ATLCAR.CD30 cells in tumor biopsies in subjects who received both ATLCAR.CD30.CCR4 and ATLCAR.CD30 cellular products

Median overall survival (OS) in subjects with CD30+ relapsed/refractory HL and CTCL after administration of ATLCAR.CD30.CCR4 with and without ATLCAR.CD30

Median progression free survival (PFS) after infusion of ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 in subjects with CD30+ relapsed/refractory HL and CTCL.

+2 more

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: ATLCAR.CD30.CCR4 & ATLCAR.CD30Experimental Treatment4 Interventions

A 3+3 design in adult subjects. Subjects in the first dose level will receive ATLCAR.CD30.CCR4 cells alone, once safety has been established, the initial dose of ATLCAR.CD30.CCR4 will be combined with a fixed dose of ATLCAR.CD30 cells in the next dose level. Every time the dose of ATLCAR.CD30.CCR4 is escalated, subjects in that dose level will receive ATLCAR.CD30.CCR4 alone prior to subsequent dose level enrolling subjects to receive a combination of fixed dose ATLCAR.CD30 and the selected dose level of ATLCAR.CD30.CCR4. The six dose levels will consist of: dose level 1 = 2 × 10\^7 ATLCAR.CD30.CCR4 cells/m2; dose level 2 = 1 × 10\^8 ATLCAR.CD30 cells/m2 and 2 × 10\^7 ATLCAR.CD30.CCR4 cells/m2; dose level 3 = 5 × 10\^7/m2 ATLCAR.CD30.CCR4 cells/m2; dose level 4 = 1 × 10\^8 ATLCAR.CD30 cells/m2 and 5 × 10\^7 ATLCAR.CD30.CCR4 cells/m2; dose level 5 = 1 × 10\^8/m2 ATLCAR.CD30.CCR4 cells/m2; dose level 6 = 1 × 108 ATLCAR.CD30 cells/m2 and 1 × 108 ATLCAR.CD30.CCR4 cells/m2.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bendamustine

2015

Completed Phase 3

~3230

Fludarabine

2012

Completed Phase 4

~1860

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

The most common treatments for immunoproliferative disorders include monoclonal antibodies, chimeric antigen receptor (CAR) T cells, and targeted therapies. Monoclonal antibodies, such as anti-CD20 and anti-CD30, work by binding to specific antigens on the surface of cancer cells, marking them for destruction by the immune system. CAR T cells are engineered to express receptors that target specific cancer antigens, such as CD30, enhancing the immune system's ability to locate and kill cancer cells. The ATLCAR.CD30.CCR4 trial combines CAR T cells targeting CD30 with CCR4 to improve tumor localization, ensuring that the modified T cells are directed more effectively to the cancerous cells. These mechanisms are crucial for patients as they offer targeted, potent, and potentially long-lasting treatments, reducing the likelihood of relapse and improving overall outcomes.

Use of a chimeric monoclonal anti-CD4 antibody in patients with refractory rheumatoid arthritis.Monoclonal antibodies against cutaneous T-cell lymphomas.Castleman's disease: from basic mechanisms to molecular therapeutics.