Study of CAR-T Cells Expressing CD30 and CCR4 for r/r CD30+ HL and CTCL

NCT03602157 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: LCCC 1606-ATLR01CA247497
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

The body has different ways of fighting infection and disease. No single way is perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from disease caused by bacteria or toxic substances. Antibodies work by binding bacteria or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with bacteria or viruses. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to treat cancer. This study will combine both T cells and antibodies in order to create a more effective treatment called Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted against the CD30 antigen (ATLCAR.CD30). Another treatment being tested includes the Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted against the CD30 antigen with CCR4 (ATLCAR.CD30.CCR4) to help the cells move to regions in the patient's body where the cancer is present. Participants in this study will receive either ATLCAR.CD30.CCR4 cells alone or will receive ATLCAR.CD30.CCR4 cells combined with ATLCAR.CD30 cells. Previous studies have shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. The new gene that is put in the T cells in this study makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma but have not been strong enough to cure most patients. For this study, the anti-CD30 antibody has been changed so instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. These CD30 chimeric (combination) receptor-activated T cells (ATLCAR.CD30) can kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown. Researchers are working to identify ways to improve the ability of ATLCAR.CD30 to destroy tumor cells. T cells naturally produce a protein called CCR4 which functions as a navigation system directing T cells toward tumor cells specifically. In this study, researchers will also genetically modify ATLCAR.CD30 cells to produce more CCR4 proteins and they will be called ATLCAR.CD30.CCR4. The study team believes that the ATLCAR.CD30.CCR4 cells will be guided directly toward the tumor cells based on their navigation system. In addition, the study team believes the majority of ATLCAR.CD30 cells will also be guided directly toward tumor cells when given together with ATLCAR.CD30.CCR4, increasing their anti-cancer fighting ability. This is the first time ATLCAR\>CD30.CCR4 cells or combination of ATLCAR.CD30.CCR4 and ATLCAR.CD30 cells are used to treat lymphoma. The purpose of this study to determine the following:

• What is the safe dose of ATLCAR.CD30.CCR4 cells to give to patients
• What is the safe dose of the combination of ATLCAR.CD30 and ATLCAR.CD30.CCR4 cells to give to patients

Conditions

Lymphoma; Immune System Diseases; Immunoproliferative Disorders; Lymphatic Diseases; Lymphoproliferative Disorders; Neoplasms; Cutaneous Lymphoma; Cutaneous Anaplastic Large Cell Lymphoma; Mycosis Fungoides; Sezary Syndrome; Lymphomatoid Papulosis; Cutaneous T Cell Lymphoma; Gray Zone Lymphoma

Keywords

CAR T cells; CD30; CCR4; Lymphoma; T lymphocytes

Outcome Measures

Primary Outcomes (1)

• Number of participants with adverse events (AE) as a measure of safety and tolerability ATLCAR.CD30.CCR4 and ATLCAR.CD30 cells

  Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, version 5.0), CRS toxicity will be graded according to the toxicity scale outlined in CRS Grading Criteria/Link to CRS Management Guidelines and ICANS will be graded according to the toxicity scale outlined in Management of Neurotoxicity/Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) from CAR-T Therapy. The MTD will be based on the rate of dose-limiting toxicity.

  6 weeks

Secondary Outcomes (6)

• 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.

  15 years

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

  15 years

• Objective response rate by 7 weeks and best overall response rate in subjects with CD30+ relapsed/refractory HL and CTCL after infusion of ATLCAR.CD30.CCR4 with and without ATLCAR.CD30

  7 weeks

• The best overall response rate

  7 weeks

• 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

  15 years

Study Arms (1)

ATLCAR.CD30.CCR4 & ATLCAR.CD30

EXPERIMENTAL

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.

Biological: ATLCAR.CD30.CCR4 cells; Biological: ALTCAR.CD30 cells; Drug: Bendamustine; Drug: Fludarabine

Interventions

ATLCAR.CD30.CCR4 cells BIOLOGICAL

Three dose levels are being evaluated: 2x10\^7, 5x10\^7, 1x10\^8

ATLCAR.CD30.CCR4 & ATLCAR.CD30

ALTCAR.CD30 cells BIOLOGICAL

Fixed dose level of 1x10\^8

ATLCAR.CD30.CCR4 & ATLCAR.CD30

Bendamustine DRUG

70 mg/m\^2/day Bendamustine for 3 days for lymphodepletion prior to cell infusion

ATLCAR.CD30.CCR4 & ATLCAR.CD30

Fludarabine DRUG

30 mg/m\^2/day Fludarabine for 3 days for lymphodepletion prior to cell infusion

ATLCAR.CD30.CCR4 & ATLCAR.CD30

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Unless otherwise noted, subjects must meet all of the following criteria to participate in this study:
• Written informed consent and HIPAA authorization for release of personal health information. Subjects or their Legally Authorized Representative must sign a consent to undergo cell procurement. Written informed consent to enroll in the CAR T-cell therapy trial must be obtained prior to lymphodepletion.
• Adults ≥18 years of age.
• Subjects must have one of the following diagnoses by WHO criteria:
• Classic Hodgkin Lymphoma
• Mycosis fungoides
• Sezary syndrome
• Primary cutaneous CD30 positive T cell lymphoproliferative disorder including lymphomatoid papulosis or primary cutaneous anaplastic large cell lymphoma
• B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin Lymphoma (Grey Zone Lymphoma)
• Diagnosis of recurrent lymphoma in subjects who have failed ≥2 prior treatment regimens.
• These prior treatment regimens must include brentuximab vedotin.
• If the subject has Hodgkin Lymphoma, the subject must have either failed autologous transplant or must not be eligible for autologous transplant.
• If the subject has grey zone lymphoma, the subject must have failed an anthracycline containing regimen unless the subject was not previously a candidate for anthracycline
• Subjects relapsed after autologous or allogeneic stem cell transplant are eligible for this study.
• CD30+ disease (result can be pending at the time of cell procurement, but must be confirmed prior to treatment with ATLCAR.CD30.CCR4 and ATLCAR.CD30 cells); NOTE: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard.

You may not qualify if:

• Pregnant or lactating.
• Tumor in a location where enlargement could cause airway obstruction.
• Current use of systemic corticosteroids at doses ≥10mg prednisone daily or its equivalent; those receiving \<10mg daily may be enrolled at discretion of the Investigator.
• Active infection with HIV, HTLV, HCV (can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells) defined as not being well controlled on therapy. Subjects are required to have negative HIV antibody, negative HTLV1 and 2 antibody, and negative HCV antibody or viral load.
• Active infection with HBV. Subjects are required to have a negative Hepatitis B surface Antigen. In addition, subjects must either have core antibody negative HBV (results can be pending at the time of cell procurement) OR if a subject is Hepatitis B core antibody positive they must have their Hepatitis B viral load checked. These subjects will be excluded if their viral load is positive at baseline. Subjects who are core antibody positive and viral load negative at baseline will be considered eligible.
• Has a known additional malignancy that is active and/or progressive requiring treatment; exceptions include basal cell or squamous cell skin cancer, in situ cervical or bladder cancer, or other cancer for which the subject has been disease-free for at least three years.
• A history of intolerance to fludarabine. Subjects with an intolerance to bendamustine may be allowed to enroll at the discretion of the clinical investigator if he/she thinks that the subject is a candidate for lymphodepletion with cyclophosphamide and fludarabine.
• Subject is not a good candidate for treatment with ATLCAR.CD30.CCR4 with and without ATLCAR.CD30 per Investigator's discretion.
• Eligibility criteria to be met prior to procurement
• Evidence of adequate organ function as defined by:
• The following is required prior to procurement:
• Hgb ≥ 8.0g/dL (transfusion independent for 2 weeks prior to enrollment)
• Bilirubin ≤1.5 times the upper limit of normal (ULN). Subjects with Gilbert's syndrome may be treated despite a total bilirubin level \>1.5 mg/dL if their conjugated bilirubin is \<1.5× ULN
• AST ≤ 3 times ULN
• Serum creatinine ≤1.5 times ULN or Creatinine Clearance (CrCl) \>60mL/min per Cockcroft and Gault

Sponsors & Collaborators

• UNC Lineberger Comprehensive Cancer Center: lead
• Stand Up To Cancer: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Related Links

• Related Info

MeSH Terms

Conditions

Lymphoma; Immune System Diseases; Immunoproliferative Disorders; Lymphatic Diseases; Lymphoproliferative Disorders; Neoplasms; Lymphoma, T-Cell, Cutaneous; Mycosis Fungoides; Sezary Syndrome; Lymphomatoid Papulosis

Interventions

Bendamustine Hydrochloride; fludarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Hemic and Lymphatic Diseases; Lymphoma, T-Cell; Lymphoma, Non-Hodgkin

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Natalie Grover, MD

  UNC Lineberger Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2018
• First Posted: July 26, 2018
• Study Start: December 12, 2018
• Primary Completion: December 16, 2025
• Study Completion (Estimated): November 4, 2039
• Last Updated: January 6, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)