Genetically Engineered Lymphocytes in Treating Patients with Metastatic Cancer or Cancer That Cannot Be Removed by Surgery Receiving Chemotherapy and Aldesleukin
Basic Trial Information
|Phase II, Phase I||Treatment||18 to 66||12-C-0111|
NCI-2013-01516, 1112-1139, 120111, P11928, RD-12-I-02, NCT01583686
This phase I/II trial studies the side effects and best dose of genetically engineered lymphocytes and to see how well it works in treating patients with cancer that has spread to other parts of the body or cancer that cannot be removed by surgery receiving chemotherapy and aldesleukin. Placing a gene that has been created in the laboratory into white blood cells may make the body build an immune response to kill cancer cells.
Further Study Information
I. To evaluate the safety of the administration of anti-mesothelin chimeric antigen receptor (CAR) engineered peripheral blood lymphocytes in patients receiving the non- myeloablative conditioning regimen, and aldesleukin.
II. Determine if the administration of anti-mesothelin CAR engineered peripheral blood lymphocytes and aldesleukin to patients following a nonmyeloablative but lymphoid depleting preparative regimen will result in clinical tumor regression in patients with metastatic or unresectable cancer that expresses mesothelin.
I. Determine the in vivo survival of CAR gene-engineered cells.
OUTLINE: This is a phase I, dose-escalation study of mesothelin-specific chimeric antigen receptor-engineered peripheral blood lymphocytes followed by a phase II study.
PREPARATIVE REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 1 hour on days -7 and -6 and fludarabine phosphate IV over 30 minutes on days -5 to -1.
CELL INFUSION AND ALDESLEUKIN ADMINISTRATION: Patients receive mesothelin-specific chimeric antigen receptor-engineered peripheral blood lymphocytes IV over 20-30 minutes on day 0 and aldesleukin IV over 15 minutes every 8 hours for up to 15 doses.
After completion of study treatment, patients are followed up at 4-6 weeks, annually for 5 years, and then periodically for 10 years.
Seronegative for human immunodeficiency virus (HIV) antibody
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 hepatitis C virus (HCV) ribonucleic acid (RNA) negative
Women of child-bearing potential must have a negative pregnancy test
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)
Note: Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to grade 1 or less
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
Serum creatinine less than or equal to 1.6 mg/dl
Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less or equal to 2.5 times the upper limit of normal
Hemoglobin greater than 8.0 g/dl
Platelet count greater than 100,000/mm^3
White blood cells (WBC) (> 3000/mm^3)
Absolute neutrophil count greater than 1000/mm^3 without the support of filgrastim
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
Life expectancy of greater than three months
Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0 or 1
Willing to sign a durable power of attorney
Patients must have previously received at least one systemic standard care (or effective salvage chemotherapy regimens) for metastatic or unresectable disease, if known to be effective for that disease, and have been either non-responders (progressive disease) or have recurred
Metastatic or unresectable measurable cancers that express mesothelin; as in other protocols conducted by Dr. Hassan in the National Cancer Institute (NCI), epithelial mesotheliomas and pancreatic cancers do not need to be assessed for mesothelin expression since all of these tumors have been shown to express mesothelin; other metastatic or unresectable cancers must be shown to expresses mesothelin as assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) or immunohistochemistry on tumor tissue; bi-phasic mesotheliomas must express mesothelin on greater than 50% of the cells in the epithelial component; diagnosis will be confirmed by the Laboratory of Pathology, NCI
Able to understand and sign the informed consent document
History of coronary revascularization or ischemic symptoms
History of severe immediate hypersensitivity reaction to any of the agents used in this study
Concurrent systemic steroid therapy
Patients with diabetic retinopathy
Concurrent opportunistic infections
Any form of primary immunodeficiency (such as severe combined immunodeficiency disease)
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
Patients receiving full dose anticoagulative therapy
Patients with known brain metastases
Women of child-bearing potential who are pregnant or breastfeeding
Patients with sarcomatoid mesothelioma as mesothelin is not expressed in this type of mesothelioma
Documented left ventricular ejection fraction (LVEF) of less than or equal to 45% 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 >= 60 years old
Trial Contact Information
Trial Lead Organizations / Sponsors / Collaborators
NCI - Center for Cancer Research
- National Cancer Institute
Mark O Hatfield-Warren Grant Magnuson Clinical Center
Steven A. Rosenberg
Steven A. Rosenberg
Link to the current ClinicalTrials.gov record.
NLM Identifer NCT01583686
Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.