• Return to search results
• Start new search

Investigator(s):
Steven A. Rosenberg, M.D., Ph.D. Principal Investigator Phone: 1-866-820-4505 (Toll Free) ncisbirc@mail.nih.gov
Referral Contact(s):
Linda Williams, R.N. Research Nurse Phone: 1-866-820-4505 (Toll Free) Fax: 301-451-1927 ncisbirc@mail.nih.gov	June A. Kryk, R.N. Research Nurse Phone: 1-866-820-4505 (Toll Free) Fax: 301-451-1927 ncisbirc@mail.nih.gov

---

Primary Eligibility:

• Histologically confirmed metastatic cancer
• Tumor expresses HER-2 at ≥ 2+ as assessed by IHC
• Progressive or recurrent disease after prior systemic standard therapy (or effective salvage chemotherapy regimens) for metastatic disease
• Patients with breast cancer must have progressed on OR not be a candidate for anthracycline-containing and taxane-containing regimens
• Patients with estrogen receptor-positive or progesterone receptor-positive breast cancer must have progressed on OR not be a candidate for anti-estrogens or aromatase inhibitors
• Patients with breast cancer must have received trastuzumab (Herceptin^®)
• Recovered from previous therapy
• ECOG 0–1
• Absolute neutrophil count > 1,000/mm³ (without filgrastim [G-CSF] support)
• WBC > 3,000/mm³
• Platelet count > 100,000/mm³
• Hemoglobin > 8 g/dL
• ALT and AST ≤ 2.5 x upper limit of normal
• Total bilirubin ≤ 1.5 mg/dL (< 3 mg/dL in patients with Gilbert’s syndrome)
• Serum creatinine ≤ 1.6 mg/dL
• LVEF ≥ 50%
• FEV₁ > 60% predicted in patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction
• Not pregnant or nursing; fertile patients must use effective contraception during and for 4 months after receiving the preparative regimen
• HIV, hepatitis C, and hepatitis B negative
• Patients who have previously received anti-CTLA4 antibody therapy must have a normal colonoscopy
• No medical condition that would preclude study participation
• No history of severe immediate hypersensitivity reaction to any of the agents used in this study

---

Treatment Plan:

This is a Phase I dose-escalation study of anti-HER-2 chimeric antigen receptor (CAR)-engineered autologous peripheral blood lymphocytes followed by a Phase II study. Patients enrolled in the Phase II portion are stratified according to cancer type (breast cancer vs. all other cancer types).

Leukapheresis and cell preparation:

• Patients undergo leukapheresis to obtain peripheral blood mononuclear cells
• The cells are then transduced by exposure to anti-HER-2 CAR retroviral vector and expanded in culture

Nonmyeloablative, lymphocyte-depleting preparative regimen:

• Patients receive cyclophosphamide IV over 1 hour on Days -7 and -6 and fludarabine phosphate IV over 30 minutes on Days -5 to -1

Anti-HER-2 CAR-engineered autologous peripheral blood lymphocyte infusion:

• Patients receive anti-HER-2 CAR-engineered autologous peripheral blood lymphocytes IV over 20–30 minutes on Day 0
• Patients also receive filgrastim (G-CSF) subcutaneously beginning on Day 1 or 2 and continuing until blood counts recover

High-dose aldesleukin:

• Patients receive high-dose aldesleukin IV over 15 minutes every 8 hours on Days 0–4 (maximum of 15 doses)

• Patients are evaluated 4–6 weeks after completion of aldesleukin
• Patients achieving partial response or stable disease (for at least 2 months) that subsequently progresses may receive another course of treatment
• Blood samples are collected periodically
• After completion of study treatment, patients are followed periodically for up to 15 years

---

Additional Information:

• This trial will be conducted at the NIH Clinical Center in Bethesda, MD. It is open to patients who meet the eligibility requirements, regardless of where they live in the United States.
• There is no charge for medical care received at NIH Clinical Center.
• PDQ (Physicians Data Query) - provides additional details about this study for health care providers.

Reviewed: 
Updated: 1/8/09