- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04577326
Mesothelin-targeted CAR T-cell Therapy in Patients With Mesothelioma
A Single-Arm, Open-Label, Phase I Trial to Assess the Safety of Genetically Engineered Autologous T Cells Targeting the Cell Surface Antigen Mesothelin With Cell-Intrinsic Checkpoint Inhibition in Patients With Mesothelioma
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Roisin O'Cearbhaill, MD
- Phone Number: 646-888-4227
- Email: cart@mskcc.org
Study Contact Backup
- Name: Adam Schoenfeld, MD
- Phone Number: 646-608-4042
Study Locations
-
-
New York
-
New York, New York, United States, 10065
- Recruiting
- Memorial Sloan Kettering Cancer Center (All Protocol Activities)
-
Principal Investigator:
- Roisin O'Cearbhaill, MD
-
Contact:
- Adam Schoenfeld, MD
- Phone Number: 646-608-4042
-
Contact:
- Roisin O'Cearbhaill, MD
- Phone Number: 646-888-4227
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Aged ≥18 years
- Karnofsky performance status ≥70%
Pathologically confirmed MPM
- Epithelioid or biphasic histologic diagnosis provided that ≥10% of the tumor expresses MSLN by IHC analysis
- Patients with peritoneal mesothelioma with pleural involvement are eligible only if there is radiographic and pathologic confirmation of mesothelioma in the pleural cavity and ≥10% of the tumor expresses MSLN by IHC analysis.
- Previously treated with at least 1 treatment regimen
- Measurable or evaluable disease (disease is considered evaluable but not measurable if it does not meet the eligibility criteria for mRECIST but is a manifestation of malignancy that can be followed qualitatively as an indicator of disease progression or treatment response)
Chemotherapy, targeted therapy, or radiotherapy must be completed at least 7 days before leukapheresis.
a. CPI must be completed at least 21 days before leukapheresis.
Chemotherapy, targeted therapy, or therapeutic radiotherapy must be completed at least 14 days before administration of T cells.
- Palliative radiotherapy can be completed 2 days before lymphodepletion. Immunotherapy with CPI must be completed at least 42 days before administration of T cells.
9. Any major thoracic (thoracotomy with lung or esophageal resection) or abdominal (laparotomy with organ resection) operation must have occurred at least 28 days before study enrollment. Patients who have undergone diagnostic VATS or laparoscopy can be included in the study.
10. All acute toxic effects of any previous therapeutic or palliative radiotherapy, chemotherapy, or surgical procedures must have resolved to grade 1 (CTCAE v5.0).
11. Lab requirements (hematology):
a. Absolute neutrophil count ≥1.5 K/mcL b. Platelet count ≥100 K/mcL
12. Lab requirements (serum chemistry):
a. Bilirubin ≤1.5x upper limit of normal (ULN) b. Serum alanine aminotransferase and serum aspartate aminotransferase (ALT/AST) level ≤5x ULN c. Serum creatinine level ≤1.5x ULN or creatinine >1.5x ULN but calculated clearances of >60 by Cockcroft-Gault Equation
13. Negative screen for infectious disease markers including Hepatitis B core antibody, Hepatitis B surface antigen, Hepatitis C antibody, HIV 1-2 antibody, HTLV 1-2 and Syphilis (rapid plasma regain profile) Note - Patients with history of prior hepatitis B virus (HBV) infection are eligible if the HBV viral load is undetectable. Patients with a history of hepatitis C virus (HCV) infection who were treated for hepatitis C and cured are eligible if hepatitis C viral load is undetectable.
14. Life expectancy at the time of screening ≥4 months
Exclusion Criteria:
Patients receiving therapy for concurrent active malignancy
a. Patients receiving treatment for in situ skin malignancies are not excluded.
- Patients who received prior CAR T-cell therapy
Untreated or active central nervous system (CNS) metastases (progressing or requiring anticonvulsants or corticosteroids for symptomatic control). Patients with a history of treated CNS metastases are eligible if all the following criteria are met:
- Presence of measurable or evaluable disease outside of the CNS
- Radiographic demonstration of improvement upon completion of CNS-directed therapy and no evidence of interim progression between completion of CNSdirected therapy and the screening radiographic study
- Completion of radiotherapy ≥8 weeks before the screening radiographic study
- Discontinuation of corticosteroids and anticonvulsants ≥4 weeks before the screening radiographic study
- History of seizure disorder
Active autoimmune disease that has required systemic treatment in the past year (with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)
a. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
- Patients who are receiving daily systemic corticosteroids that are above physiological doses for any reason or who are under immunosuppressive or immunomodulatory treatment
Patients with the below cardiac conditions:
- New York Heart Association stage III or IV congestive heart failure
- Myocardial infarction ≤6 months before enrollment
- History of myocarditis
- Serious uncontrolled cardiac arrhythmia, unstable angina, or uncontrolled infection
- Patients with left ventricular ejection fraction ≤40%
- Patients with active interstitial lung disease/pneumonitis or a history of interstitial lung disease/pneumonitis requiring treatment with systemic steroids
- Baseline pulse oximetry <90% on room air at the screening timepoint
Pregnant or lactating women
a. Subjects and their partners with reproductive potential must agree to use an effective form of contraception during treatment and for 1 year following treatment.
- Known active infection requiring antibiotic treatment 7 days before the start of treatment (Day 0). Note: treatment can be delayed at the discretion of the treating physician to allow the patient to recover from the infection.
- Administration of live, attenuated vaccine within 8 weeks before the start of treatment (Day 0) and for 100 days following treatment.
- Any other medical condition that, in the opinion of the PI, may interfere with a subject's participation in or compliance with the study
- Any patient deemed to be noncompliant by the study team for administration of a high risk treatment agent and for close follow-up after treatment as required by the protocol
- Patients with known hematologic malignancy requiring treatment in the preceding 5 years or a known history of lymphoid malignancy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Engineered Autologous T Cells
Following eligibility screening and enrollment, patients will undergo leukapheresis for the collection of peripheral blood mononuclear cells (PBMCs), to enable generation of M28z1XXPD1DNR.
Following successful M28z1XXPD1DNR CAR T-cell manufacturing, patients will be reevaluated for eligibility.
A preconditioning regimen of one dose of intravenous (IV) cyclophosphamide 1.5 g/m2 will be administered 2-7 days before the infusion.
A single dose of M28z1XXPD1DNR CAR T cells will be instilled into the pleural cavity via a pleural catheter or through an interventional radiology-guided needle.
All patients will be monitored in the hospital for a minimum of 48 h following the administration of CAR T cells.
|
A preconditioning regimen of one dose of intravenous (IV) cyclophosphamide 1.5 g/m^2 will be administered 2-7 days before the infusion.
A single dose of M28z1XXPD1DNR CAR T cells will be instilled into the pleural cavity via a pleural catheter or through an interventional radiology-guided needle.
Cohorts of 3 patients will be treated at each dose level, up to a maximum of 3 x 10^7 T cells/kg or until the MTD has been reached.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MTD of M28z1XXPD1DNR
Time Frame: 2 years
|
CTCAE v5.0 will be used to assess the severity of all treatment emerging toxicities/adverse events regardless
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
overall response rate (ORR)
Time Frame: 2 years
|
modified RECIST (mRECIST; v1.0)
|
2 years
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Roisin O'Cearbhaill, MD, Memorial Sloan Kettering Cancer Center
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Respiratory Tract Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Neoplasms, Glandular and Epithelial
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Lung Neoplasms
- Adenoma
- Neoplasms, Mesothelial
- Pleural Neoplasms
- Mesothelioma
- Mesothelioma, Malignant
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Cyclophosphamide
Other Study ID Numbers
- 20-328
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malignant Pleural Mesothelioma (MPM)
-
Ontario Clinical Oncology Group (OCOG)Novartis PharmaceuticalsTerminatedAdvanced Malignant Pleural Mesothelioma | MPMCanada
-
National Cancer Institute (NCI)WithdrawnMalignant Pleural Mesotheliomas (Mpm) | Malignant Pleural Effusions (Mpe) | Epithelial Tumors, Malignant | Pleural Effusions, Malignant | Mesothelin (Msln)United States
-
University of ChicagoWithdrawnMalignant Pleural Mesothelioma (MPM)United States
-
Assistance Publique Hopitaux De MarseilleCompletedNon Small Cell Lung Cancer (NSCLC) | Malignant Pleural Mesothelioma (MPM)France
-
Memorial Sloan Kettering Cancer CenterPfizerCompletedMalignant Mesothelioma (MPM)United States
-
NRG OncologyNational Cancer Institute (NCI)TerminatedPleural Biphasic Mesothelioma | Pleural Epithelioid Mesothelioma | Stage I Pleural Malignant Mesothelioma AJCC v8 | Stage IA Pleural Malignant Mesothelioma AJCC v8 | Stage IB Pleural Malignant Mesothelioma AJCC v8 | Stage II Pleural Malignant Mesothelioma AJCC v8 | Stage IIIA Pleural Malignant...United States, Canada
-
University of ChicagoNational Cancer Institute (NCI)Active, not recruitingBiphasic Mesothelioma | Epithelioid Mesothelioma | Peritoneal Malignant Mesothelioma | Pleural Biphasic Mesothelioma | Pleural Epithelioid Mesothelioma | Pleural Malignant Mesothelioma | Pleural Sarcomatoid Mesothelioma | Recurrent Peritoneal Malignant Mesothelioma | Recurrent Pleural Malignant Mesothelioma and other conditionsUnited States
-
National Cancer Institute (NCI)Active, not recruitingBiphasic Mesothelioma | Epithelioid Mesothelioma | Stage III Pleural Malignant Mesothelioma AJCC v7 | Stage I Pleural Malignant Mesothelioma AJCC v7 | Stage IA Pleural Malignant Mesothelioma AJCC v7 | Stage IB Pleural Malignant Mesothelioma AJCC v7 | Stage II Pleural Malignant Mesothelioma AJCC...United States
-
RS Oncology LLCRecruitingMesothelioma | Malignant Pleural Mesothelioma | Pleural Effusion, Malignant | Mesotheliomas Pleural | Malignant Pleural Effusion | Mesothelioma; LungUnited Kingdom
-
Health Pharma Professional ResearchWithdrawnMalignant Pleural Mesothelioma, Advanced | Malignant Pleural Mesothelioma, UnresectableMexico
Clinical Trials on cyclophosphamide
-
Children's Hospital Los AngelesLucile Packard Children's HospitalTerminatedMetabolic Diseases | Stem Cell Transplantation | Chronic Granulomatous Disease | Bone Marrow Transplantation | Thalassemia | Wiskott-Aldrich Syndrome | Genetic Diseases | Peripheral Blood Stem Cell Transplantation | Pediatrics | Diamond-Blackfan Anemia | Allogeneic Transplantation | Combined Immune Deficiency | X-linked Lymphoproliferative Disease
-
Medical College of WisconsinNational Cancer Institute (NCI); National Heart, Lung, and Blood Institute... and other collaboratorsCompletedAnemia, AplasticUnited States
-
Columbia UniversityUnknownSevere Combined Immunodeficiency | Fanconi Anemia | Bone Marrow Failure | OsteopetrosisUnited States
-
National Cancer Institute, NaplesImmatics Biotechnologies GmbH; CureVac; European Commission -FP7-Health-2013-Innovation-1CompletedHepatocellular CarcinomaBelgium, Germany, Italy, Spain, United Kingdom
-
Eisai Inc.CompletedBreast Cancer | Ovarian Cancer | Prostate Cancer | Colon Cancer | Renal CancerUnited States
-
Mahidol UniversityTerminatedRenal Insufficiency | InfectionThailand
-
Centre Oscar LambretCompleted
-
Baylor Research InstituteCompletedMalignant Melanoma Stage IVUnited States
-
University of Turin, ItalyUnknown
-
Merck KGaA, Darmstadt, GermanyCompleted