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CD30 CAR for Relapsed/Refractory CD30+ T Cell Lymphoma

ConditionPeripheral T Cell Lymphoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18-99
SponsorUNC Lineberger Comprehensive Cancer Center

About this trial

This is a research study to determine the safety and tolerability of ATLCAR.CD30 for treating relapsed/refractory Peripheral T Cell Lymphoma. Blood samples will be collected from study participants and the immune T cells will be separated. T cells will be genetically modified in a laboratory at UNC-Chapel Hill to enable them to produce CD30 antibody. The modified T cells, called ATLCAR.CD30, will be able to target and attach to lymphoma cancer cells that carry the CD30 antigen. Once they are attached, the hope is that the T cells will attack and destroy the lymphoma cancer cells. To prepare the body for the ATLCAR.CD30 cells, participants will complete lymphodepletion with two chemotherapy agents. Lymphodepletion will happen over three days prior to ATLCAR.CD30 infusion. If participants respond to this treatment, and there are sufficient unused ATLCAR.CD 30 cells, they may be eligible to receive a second infusion. The second infusion will be given after a second lymphodepletion chemotherapy. Most of the clinic visits in this research will last between 1-8 hours.

There are risks associated in participating in this research study. Risks of treatment include infection, fever, nausea, vomiting, neurotoxicity, and cytokine release syndrome which can include low blood pressure or difficulty breathing. Other risks are associated with study procedures, such as biopsies, imaging, infusion, and breach of confidentiality.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Written informed consent and HIPAA authorization for release of personal health information explained to, understood by and signed by the subject or legally authorized representative.

Age ≥ 18 years at the time of consent.

Karnofsky score of >60%

Histological or cytological evidence/confirmation of CD30+ peripheral T-cell lymphoma per the 2017 World Health Organization Classification of Haematopoietic and Lymphoid Tissues.

Disqualifiers

Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study ).

Current use of systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent; those receiving <10 mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed.

Active infection with HIV, HTLV, HCV (tests can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells). Note: To meet eligibility subjects are required to be negative for HIV antibody, negative for HTLV1 and 2 antibody or PCR negative for HTLV1 and 2, negative for HCV antibody or HCV viral load.

Subjects who are positive for hepatitis B surface antigen (can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells) are excluded. Subjects who are hepatitis B surface antigen negative but hepatitis B core antibody positive 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.

Trial design

Design model

Single group

Treatments tested in this trial

  • ATLCAR.CD30 T cells

    Biological/Vaccine

    Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted against the CD30 antigen at dose of 2 × 10\^8 CAR-T/m\^2 with a maximum dose of 5 × 10\^8 CAR-T cells

  • Bendamustine

    Drug

    70 mg/m\^2 administered IV for 3 days for lymphodepletion 2-14 days prior to first cell infusion

  • Fludarabine

    Drug

    30 mg/m\^2 administered IV for 3 days for lymphodepletion 2-14 days prior to first and second cell infusion

  • Cyclophosphamide

    Drug

    300 mg/m\^2 administered IV for 3 days for lymphodepletion 2-14 days prior to second cell infusion and 2-14 days prior to the first cell infusion for subjects who have previously had hypersensitivity to bendamustine

Treatment groups

20 Participants
are divided into 1 treatment group
Group A: ATLCAR.CD30 cellsExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

Progression free survival (PFS) after administration of the ATLCAR.CD30 in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma

PFS is defined from day of initial lymphodepletion administration of the first ATLCAR.CD30 product infusion to the date of disease progression per the Revised Lugano Criteria or death as a result of any cause. Subjects who do not meet criteria for progression by the analysis data cut-off date will be censored at their last evaluable disease assessment date.

Time frame
8 weeks

Secondary outcomes

1

Best overall response rate (BOR) mediated by the ATLCAR.CD30 product administered in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma

The best overall response rate (BOR) will be defined as the best response recorded from the first administration of the ATLCAR.CD30 product to the date of disease progression per the Revised Lugano Criteria or death as a result of any cause.

Time frame
2 years
2

Objective response rate (ORR) mediated by the first infusion of the ATLCAR.CD30 product administered in patients with relapsed/refractory CD30+ peripheral T cell lymphoma.

The objective response rate (ORR) will be defined as the rate of complete responses (CR) + partial responses (PR) by 8 weeks from the date of first lymphodepletion prior to the first administration of the ATLCAR.CD30 product per the Revised Lugano Criteria.

Time frame
8 weeks
3

Responses improved by the second infusion of the ATLCAR.CD30 product administered in subjects with either partial response or stable disease following the first infusion of ATLCAR.CD30

The percentage of subjects who have an improvement in their response after the second administration of ATLCAR.CD30 product will be defined at 8 weeks after the second administration of the ATLCAR.CD30 product per the Revised Lugano Criteria. Subjects entering the second infusion in a complete response will be reported as continued CR (CCR) but will not be included in percentage of improved responses after the second infusion.

Time frame
8 weeks
4

Incidence of Dose Limiting Toxicity (DLT) (safety and tolerability) when administering two sequential infusions of the ATLCAR.CD30 product in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma

DLT defined as ≥ Grade 3 cytokine release syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), or any other ≥ Grade 3 non-hematologic toxicity, including allergic reactions to T cell infusions. 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 CRS Grading Criteria and Management Guidelines Version 3.0 (March 14, 2019). ICANS toxicity will be graded according to the ICANS Grading Criteria for Management of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) for CAR T-Cell Therapy.

Time frame
8 weeks

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

UNC Lineberger Comprehensive Cancer Center

Lead sponsor

Source ClinicalTrials.gov
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