Phase 2
N=24
Phase II Study of Metastatic Melanoma With Lymphodepleting Conditioning and Infusion of Anti-MART-1 F5 TCR-Gene-Engineered Lymphocytes
Melanoma · Skin Cancer
Bottom Line
View on ClinicalTrials.gov: NCT00509288 ↗Enrolled (actual)
24
Serious AEs
16.7%
Results posted
Dec 2012
Primary outcome: Primary: Clinical Tumor Regression. — 0; 0; 6; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- autologous anti-MART-1 F5 T-cell receptor (Biological); Cyclophosphamide (Drug); Fludarabine (Drug); Aldesleukin (Biological); autologous anti-MART-1 F5 T-cell receptor gene-engineered tumor infiltrating lymphocytes (Biological)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- National Cancer Institute (NCI)
- Primary completion
- Jul 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Clinical Tumor Regression. |
0; 0; 6; 0; 15; 2 | — |
| SECONDARY Toxicity |
21; 3 | — |
Summary
Background:
* Human peripheral blood lymphocytes have been engineered to express a T-cell receptor (TCR) that recognizes a blood type,HLA-A 0201 (human leukocyte antigen) derived from the gp100 protein. A retroviral vector was constructed that can deliver the T-cell receptor (TCR) to cells.
* Patients' cells will be converted into cells able to recognize and fight melanoma tumors.
Objectives:
* To determine whether TCR-engineered lymphocytes can be put in cells removed from patients' tumors or blood and then reinfused, with the purpose of shrinking tumors.
* To evaluate safety and effectiveness of the treatment.
Eligibility:
* Patients 18 years of age or older with metastatic cancer melanoma (cancer that has spread beyond the original site).
* Patient's leukocyte antigen type is HLA-A 0201.
Design:
-Patients undergo the following procedures:
* Leukapheresis (on two occasions). This is a method of collecting large numbers of white blood cells. The cells obtained in the first leukapheresis procedure are grown in the laboratory, and the anti-MART-1 protein is inserted into the cells using an inactivated (harmless) virus in a process called retroviral transduction. Cells collected in the second leukapheresis procedure are used to evaluate the effectiveness of the study treatment.
* Chemotherapy. Patients are given chemotherapy through a vein (intravenously, IV) over 1 hour for 2 days to suppress the immune system so that the patient's immune cells do not interfere with the treatment.
* Treatment with anti-melanoma antigen recognized by T-cells (MART)-1. Patients receive an intravenous (IV) infusion of the treated cells containing anti-MART-1 protein, followed by infusions of a drug called IL-2 (aldesleukin), which helps boost the effectiveness of the treated white cells.
* Patients are given support medications to prevent complications such as infections.
* Patients may undergo a tumor biopsy (removal of a small piece of tumor tissue).
* Patients are evaluated with laboratory tests and imaging tests, such as CT (computed tomography) scans, 4 to 6 weeks after treatment and then once a month for 3 to 4 months to determine the response to treatment.
* Patients have blood tests at 3, 6, and 12 months and then annually for 5 years.
Eligibility Criteria
- INCLUSION CRITERIA:
- Metastatic melanoma with measurable disease
- Previously received high dose IL-2 (aldesleukin) and have been either non-responders (progressive disease) or have recurred.
- Positive for MART-1 by immunohistochemistry (IHC)
- Greater than or equal to 18 years of age.
- Willing to sign a durable power of attorney
- Able to understand and sign the Informed Consent Document
- Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1.
- Life expectancy of greater than three months.
- Patients of both genders must be willing to practice birth control for four months after receiving the preparative regimen.
- Patients must be human leukocyte antigen (HLA-A)*0201 positive
- Serology:
- 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.)
- Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative.
- Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the preparative chemotherapy on the fetus.
l. Hematology:
- Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim.
- White blood cell (WBC) (greater than 3000/mm^3).
- Platelet count greater than 100,000/ mm^3.
- Hemoglobin greater than 8.0 g/dl.
m. Chemistry:
- Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of normal.
- 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.
n. 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).
o. Six weeks must have elapsed since prior anti-CTLA4 antibody therapy to allow antibody levels to decline.
p. Patients who have previously received anti-CTLA4 antibody must have a normal colonoscopy with normal colonic biopsies.
EXCLUSION CRITERIA
- Patients with reactive TIL (IFN-gamma release greater than 200 pg/mL) available based on overnight co-culture assay with autologous tumor or MHC-matched tumor cells.
- Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
- 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.
- Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
- 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).
- Systemic steroid therapy.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- History of coronary revascularization or ischemic symptoms.
- Any patient known to have an left ventricular ejection fraction (LVEF) less than or equal to 45 percent.
- Documented LVEF of less than or equal to 45 percent tested in patients with:
- Clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block.
- Age greater than or equal to 60 years old.
- Documented forced expiratory volume 1 (FEV1) le
Data sourced from ClinicalTrials.gov (NCT00509288). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.