Administering Peripheral Blood Lymphocytes Transduced With a CD70-Binding Chimeric Antigen Receptor to People With CD70 Expressing Cancers
- Conditions
- Renal Cell CancerBreast CancerMelanomaPancreatic CancerOvarian Cancer
- Interventions
- Registration Number
- NCT02830724
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
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.
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- Detailed 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:
* Age \>= 18 years and \<= 72 years
* 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 124
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 1/Phase I Fludarabine Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + escalating doses of anti-hCD70 CAR transduced PBL + high-dose aldesleukin 2/Phase II Anti-hCD70 CAR transduced PBL Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + MTD of anti-hCD70 CAR transduced PBL + high-dose aldesleukin 1/Phase I Anti-hCD70 CAR transduced PBL Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + escalating doses of anti-hCD70 CAR transduced PBL + high-dose aldesleukin 1/Phase I Aldesleukin Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + escalating doses of anti-hCD70 CAR transduced PBL + high-dose aldesleukin 1/Phase I Cyclophosphamide Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + escalating doses of anti-hCD70 CAR transduced PBL + high-dose aldesleukin 2/Phase II Cyclophosphamide Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + MTD of anti-hCD70 CAR transduced PBL + high-dose aldesleukin 2/Phase II Fludarabine Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + MTD of anti-hCD70 CAR transduced PBL + high-dose aldesleukin 2/Phase II Aldesleukin Non-myeloablative, lymphodepleting preparative regimen of cyclophosphamide and fludarabine + MTD of anti-hCD70 CAR transduced PBL + high-dose aldesleukin
- Primary Outcome Measures
Name Time Method Frequency and severity of treatment-related adverse events From time of cell infusion to two weeks after cell infusion Grade and type of toxicity per dose level; fraction of patients who experience a DLT at a given dose level, and number and grade of each type of DLT
Response rate 6 weeks and 12 weeks following administration of the cell product, then every 3 months x3, then every 6 months x 2 years, then per PI discretion Percentage of patients who have a clinical response (PR+CR) to treatment (objective tumor regression)
- Secondary Outcome Measures
Name Time Method Frequency and severity of treatment-related adverse events 6 weeks ( plus or minus 2 weeks) following administration of the cell product Aggregate of all adverse events, as well as their frequency and severity
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States