Phase 1 Clinical Trial of Autologous Mesothelin Re-Directed T Cells Administered Intravenously in Patients With Progressive Malignant Pleural Mesothelioma
- Subjects must have histologically confirmed MPM (epithelial or biphasic).
- Subjects must have completed standard first line therapy with a platinum-based double
regimen and had PD or they must have chosen not to pursue primary standard of care
- ECOG performance status 0 to 1.
- Age greater than 18 years
- Life expectancy > 4 months
- At least 2 weeks since prior and no other concurrent chemotherapy, radiotherapy, or
immunotherapy (e.g., interferons, tumor necrosis factor, interleukins, or monoclonal
antibodies). In addition, the patient must have fully recovered from any adverse
events related to these agents.
- More than 4 weeks since prior and no other concurrent investigational agents.
- Subjects must have measurable disease as defined by accepted MPM measurement
techniques (modified RECIST criteria).
- Blood coagulation parameters: PT such that international normalized ratio (INR) is <
1.5 (or an in-range INR, usually between 2 and 3, if a subject is on a stable dose of
therapeutic warfarin for management of venous thrombosis including pulmonary
thromboembolus) and a PTT < 1.2 times the upper limit of normal.
- Subjects must have adequate venous peripheral access for apheresis. Patients must
also have adequate venous access for subsequent modified CIR T-cell administration
which can be done through a central venous access (e.g. port of systemic
- Short-term therapy for acute conditions not specifically related to MPM is allowed if
such therapy does not include any immune modulating agents.
- Male and Female subjects agree to use approved contraceptive methods (e.g. birth
control pills, barrier device, intrauterine device , abstinence) during the study and
for 3 months following the last dose of the study cell infusion.
- Subject must understand and sign the study-specific informed consent .
- Satisfactory organ and bone marrow function as defined by :
Absolute neutrophil count > 1,000/µl Platelets > 100,000/µl Hematocrit > 30 %
AST(SGOT)/ALT(SGPT) < 3x the institutional normal upper limit Bilirubin < 2.0 mg/dL unless
secondary to malignant bile duct obstruction Creatinine < 1.5x the institutional normal
- Previously treated with any investigation therapy within 1 month prior to screening.
- Sacromatoid MPM histology which does not express mesothelin
- Prior invasive malignancies unless surgically and medically cured without evidence of
recurrent disease for 5 years with the exception of non-melanoma skin cancer,
prostate cancer with PSA level < 1.0.
- Prior hematologic malignancy with bone marrow transplantation or immune modifying
therapy within the past 4 weeks with the exception of thyroid replacement.
- Use of immunosuppressive drugs with 4 weeks prior to study entry, or anticipated use
of immunosuppressive agents.
- Any clinically -significant pericardial effusion, CHF (NY Heart Association Grade
II-IV ), or cardiovascular condition.
- Any clinically -significant pleural effusion or ascites that cannot be drained with
standard approaches or with pre-enrollment in dwelling drainage device placement.
- Forced vital capacity < 50% predicted, DLCO < 40% predicted.
- Underlying lung disease requiring supplemental oxygen therapy.
- Have a recognized immunodeficiency disease including cellular immunodeficiency,
hypogammaglobulinemia, or dysgammaglobulinemia; patients who have acquired
hereditary, congenital immunodeficiency.
- Viral infections: HIV, HCV, HBV.
- Pregnant women are excluded from this study because autologous transduced T cells,
breastfeeding should be discontinued if the mother is treated.
- Feasibility assessment during screening demonstrates < 30% transfection of target
lymphocytes, or < 5-fold expansion in modified CIR T-cells in response to CD3/CD28