Last updated on August 2020

Administering Peripheral Blood Lymphocytes Transduced With a CD70-Binding Chimeric Antigen Receptor to People With CD70 Expressing Cancers


Brief description of study

Background

In a new cancer therapy, researchers take a person s blood, select a certain white blood cell to grow in the lab, and then change the genes of these cells using a virus. The cells are then given back to the person. This is called gene transfer. For this study, researchers will modify the person s white blood cells with anti-CD70.

Objectives

To see if a gene transfer with anti-CD70 cells can safely shrink tumors and to be certain the treatment is safe.

Eligibility

Adults age 18 and older diagnosed with cancer that has the CD70-expressing cancer.

Design

Participants will be screened with medical history, physical exam, scans, and other tests. They may by admitted to the hospital. Leukapheresis will be performed. For this, blood is removed through a needle in the arm. A machine separates the white blood cells. The rest of the blood is returned through a needle in the other arm.

Eligible participants will have an intravenous catheter placed in their upper chest. Over several days, they will get chemotherapy drugs and the anti-CD70 cells. They will recover in the hospital.

Participants will take an antibiotic for 6 months after treatment. They will repeat leukapheresis.

Participants will visit the clinic every 1-3 months for the first year after treatment, every 6 months for the second year, and then as determined by their physician. Follow-up visits will take 1-2 days. At each visit, participants will have lab tests, imaging studies, and a physical exam.

Throughout the study, blood will be taken and participants will have many tests to determine the size and extent of their tumor and the treatment s impact.

Detailed Study Description

Background
  • We generated a chimeric antigen receptor (CAR) that engages CD70 using its natural ligand CD27, as the binding moiety. Transducing peripheral blood lymphocytes (PBL) with this CAR conveys major histocompatibility complex (MHC)-independent recognition of CD70-expressing target cells, which include renal cell carcinoma and other cancers.
  • In co-cultures with CD70+ target cells, anti-hCD70 CAR transduced T cells secrete significant amounts of IFN-gamma with high specificity.
    Objectives

Primary objectives:

  • Phase I: Determine the safety of administering PBL transduced with anti-hCD70 CAR in concert with preparative lymphodepletion and high dose interleukin-2 (IL-2; aldesleukin).
  • Phase II: Determine if anti-hCD70 CAR-transduced PBL can mediate the regression of CD70 expressing tumors.
    Eligibility
  • Patients must be/have:

--Metastatic or unresectable CD70-expressing cancer which has progressed after standard therapy

  • Patients may not have:
  • Allergies or hypersensitivities to high-dose aldesleukin, cyclophosphamide, or fludarabine.
    Design
  • This is a phase I/II, single center study of PBL transduced with anti-hCD70 CAR in patients with measurable, unresectable cancer expressing CD70.
  • PBMC obtained by leukapheresis will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell growth.
  • Transduction is initiated by exposure of these cells to retroviral vector supernatant containing replication-incompetent virus encoding the anti-hCD70 CAR.
  • All patients will receive a non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine.
  • On day 0, patients will receive PBL transduced with the anti-hCD70 CAR and will then begin high-dose aldesleukin.
  • A complete evaluation of lesions will be conducted approximately 6 weeks (plus or minus two weeks) after treatment.
  • The study will be conducted using a Phase I/II optimal design, with two separate cohorts for the Phase II component:Cohort 2a, patients with CD70-expressing clear cell renal cell carcinoma (RCC), and Cohort 2b, patients with a CD70-expressing non-RCC malignancy (solid tumors only).
  • A total of up to 124 patients may be required; approximately 38 patients in the Phase I portion of the study and 43 (41, plus an allowance of up to 2 non-evaluable) patients in each cohort of the Phase II portion of the study.

Clinical Study Identifier: NCT02830724

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Recruitment Status: Open


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