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

• Status: Suspended
• Trial end date: 2028-01-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Vidarabine

Criteria

• INCLUSION CRITERIA:

• For Phase I: Evaluable, unresectable cancer expressing CD70 as assessed by immunohistochemistry of resected tissue (greater than or equal to 2+ CD70 positive on greater than or equal to 50% of cancer cells, or greater than or equal to 1+ CD70 positive on greater than or equal to 75% of cancer cells).

• For Phase II: Measurable (per RECIST v1.1 criteria), unresectable cancer expressing CD70 as assessed by immunohistochemistry of resected tissue (greater than or equal to 2+ CD70 positive on greater than or equal to 50% of cancer cells, or greater than or equal to 1+ CD70 positive on greater than or equal to 75% of cancer cells).

• Confirmation of the diagnosis of cancer by the NCI Laboratory of Pathology.

• Patients must have previously received at least one standard therapy for their cancer (if available) and have been either non-responders (progressive disease) or have recurred.

• Patients with 3 or fewer brain metastases that are less than or equal to 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.

• Age greater than or equal to 18 years and less than or equal to 70 years.

• Clinical performance status of ECOG 0 or 1

• Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after treatment.

• Serology

• Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive may have decreased immune-competence and thus be less responsive to the experimental

treatment and more susceptible to its toxicities.)

• Seronegative for hepatitis B antigen, and seronegative for hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.

-Hematology

• ANC greater than 1000/mm(3) without the support of filgrastim

• WBC greater than or equal to 3000/mm(3)

• Platelet count greater than or equal to 100,000/mm(3)

• Hemoglobin > 8.0 g/dL. Subjects may be transfused to reach this cut-off.

-Chemistry

• Serum ALT/AST less than or equal to 5.0 times ULN

• Serum creatinine less than or equal to 1.6 mg/dL

• Total bilirubin less than or equal to 1.5 mg/dL, except in patients with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dL.

• More than four weeks must have elapsed since completion of any prior systemic therapy at the time of enrollment.

Note: Patients may have undergone minor surgical procedures or limited field radiotherapy within the four weeks prior to enrollment, as long as related major organ toxicities have recovered to grade 1 or less.

• Ability of subject to understand and the willingness to sign a written informed consent document.

• Willing to sign a durable power of attorney.

• Subjects must be co-enrolled on the NCI-SB cell harvest protocol 03-C-0277 (Cell Harvest and Preparation for Surgery Branch Adoptive Cell Therapy Protocols).

EXCLUSION CRITERIA:

• Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.

• Concurrent systemic steroid therapy.

• Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.

• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).

• History of major organ autoimmune disease.

• Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune-competence may be less responsive to the experimental treatment and more susceptible to its toxicities).

• History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.

• History of coronary revascularization or ischemic symptoms.

• Documented LVEF less than or equal to 45% tested in patients:

• Age greater than or equal to 65 years

• With clinically significant atrial and/or ventricular arrhythmias, including but not limited to: atrial fibrillation, ventricular tachycardia, second- or third-degree heart block, or have a history of ischemic heart disease and/or chest pain.

• Who have had prior treatment with significant exposure to anthracyclines or cyclophosphamide.

• Documented FEV1 less than or equal to 60% predicted tested in patients with:

• A prolonged history of cigarette smoking (greater than or equal to 20 pack-year smoking history, with cessation within the past 2 years).

• Symptoms of respiratory dysfunction

• Patients who are receiving any other investigational agents.