CAR T Cell Receptor Immunotherapy Targeting VEGFR2 for Patients With Metastatic Cancer

• Status: Terminated
• Trial end date: 2015-12-15
• Target enrollment: 0
• Participant gender: All

Summary

Background:

The National Cancer Institute (NCI) Surgery Branch has developed an experimental therapy for treating patients metastatic cancer that involves taking white blood cells from the patient, growing them in the laboratory in large numbers, genetically modifying these specific cells with a type of virus (retrovirus) to attack only the tumor cells, and then giving the cells back to the patient. This type of therapy is called gene transfer. In this protocol, we are modifying the patient s white blood cells with a retrovirus that has the gene for anti-vascular endothelial growth factor receptor (VEGFR2) incorporated in the retrovirus.

Objectives:

• To determine a safe number of these cells to infuse and to see the safety and effectiveness of cell therapy using anti-VEGFR2 gene modified tumor white blood cells to treat recurrent or relapsed cancer.

Eligibility:

• Individuals greater than or equal to 18 years of age and less than or equal to 70 years of age who have been diagnosed with metastatic cancer that has not responded to or has relapsed after standard treatment.

Design:

• Work up stage: Patients will be seen as an outpatient at the National Institutes of Health (NIH) clinical Center and undergo a history and physical examination, scans, x-rays, lab tests, and other tests as needed

• Leukapheresis: If the patients meet all of the requirements for the study they will undergo leukapheresis to obtain white blood cells to make the anti-VEGFR2 cells. {Leukapheresis is a common procedure which removes only the white blood cells from the patient.}

• Treatment: Once their cells have grown the patients will be admitted to the hospital for the conditioning chemotherapy, the anti-VEGFR2 cells and aldesleukin. They will stay in the hospital for about4 weeks for the treatment.

• Follow up: Patients will return to the clinic for a physical exam, review of side effects, lab tests, and scans about every 1-3 months for the first year, and then every 6 months to 1 year as long as their tumors are shrinking. Follow up visits will take up to 2 days.

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

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Aldesleukin; Cyclophosphamide; Fludarabine; Fludarabine phosphate; Interleukin-2

Criteria

• INCLUSION CRITERIA:

1. Metastatic cancer with evaluable disease.

2. Patients must have previously received at least one systemic standard care (or effective salvage chemotherapy regimens) for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred.

3. Greater than or equal to 18 years of age and less than or equal to 70 years of age.

4. Willing to sign a durable power of attorney

5. Able to understand and sign the Informed Consent Document

6. Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.

7. Life expectancy of greater than three months.

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

9. Serology:

1. Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immune-competence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)

2. 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 reverse transcription-polymerase chain reaction (RT-PCR) and be hepatitis C virus (HCV) ribonucleic acid (RNA) negative.

10. Hematology:

1. Absolute neutrophil count greater than 1000/mm(3) without the support of filgrastim.

2. White blood cell (WBC) (> 3000/mm(3)).

3. Platelet count greater than 100,000/mm(3).

4. Hemoglobin greater than 8.0 g/dl.

11. Chemistry:

1. Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of normal.

2. Serum creatinine less than or equal to 1.6 mg/dl.

3. Total bilirubin less than or equal to 1.5 mg/dl, except in patients with Gilberts Syndrome who must have a total bilirubin less than 3.0 mg/dl.

12. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).

13. More than 4 weeks must have elapsed since an surgical procedure at the time the patient receives the preparative regimen due to the inhibition of wound healing observed with vascular endothelial growth factor receptor (VEGFR) targeting angiogenesis inhibitors.

EXCLUSION CRITERIA:

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

2. Patients with known brain metastases.

3. Patients receiving full dose anticoagulative therapy.

4. Active systemic infections, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive or restrictive pulmonary disease.

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

6. 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).

7. Patients with diabetic retinopathy.

8. Concurrent Systemic steroid therapy.

9. History of severe immediate hypersensitivity reaction to any of the agents used in this study.

10. History of coronary revascularization or ischemic symptoms.

11. In patients

Documented forced expiratory volume 1 (FEV1) less than or equal to 45% predicted tested in patients with:

1. History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block.

2. Age greater than or equal to 60 years old.