Treating Cancer With Anti-mesothelin Modified Lymphocytes

This study is currently recruiting participants.
Verified November 2013 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ) Identifier:
First received: April 20, 2012
Last updated: March 14, 2014
Last verified: November 2013


- A possible new procedure for treating people with advanced cancer uses blood cells known as peripheral blood cells. Once these cells are modified and grown in a laboratory, they can be used to target and destroy cancer cells. Some cells can be modified to target a protein called mesothelin that is found on some types of cancer cells. By blocking mesothelin, it is expected that these cells will help shrink existing tumors. However, it is possible that the cells will not have this effect. Researchers want to try this therapy on people who have advanced cancer that has not responded to standard treatments.


- To test the safety and effectiveness of anti-mesothelin modified cells for advanced cancer.


- Individuals at greater than or equal to 18 years of age and less than or equal to 66 years of age with advanced cancer that involves mesothelin and has not responded to standard treatments.


  • Participants will be screened with a physical exam and medical history. They will also have imaging studies before starting treatment. Blood and urine samples will be collected.
  • Participants will have leukapheresis to collect peripheral blood cells. These cells will be modified for the treatment.
  • Participants will have chemotherapy to prepare the immune system to receive the modified cells. The chemotherapy will take place for 1 week before the cell infusion.
  • Participants will receive their modified cells as an infusion. They will also receive interleukin-2 to help boost their immune system response. The interleukin-2 will be given every 8 hours for up to 15 doses.
  • Participants will recover from the infusion treatment in the hospital for at least 2 weeks.
  • The results of the treatment will be monitored with frequent follow-up blood tests and imaging studies.

Condition Intervention Phase
Metastatic Cancer
Pancreatic Cancer
Ovarian Cancer
Lung Cancer
Drug: Fludarabine
Drug: Cycolphosphamide
Biological: Aldesleukin
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Metastatic Cancer Using Lymphodepleting Conditioning Followed by Infusion of Anti-mesothelin Gene Engineered Lymphocytes

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Evaluate safety of anti-mesothelin CAR engineered PBL in patients receiving the protocol regimen.
  • Determine if anti-mesothelin CAR engineered PBL and aldesleukin to patients following the protocol regimen will result in clinical tumor regression.

Secondary Outcome Measures:
  • Determine the in vivo survival of CAR gene engineered cells.

Estimated Enrollment: 136
Study Start Date: March 2012
Estimated Study Completion Date: April 2018
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Non-myeloablative chemotherapy regimen (fludarabine and cyclophosphamide), anti-mesothelin CAR PBL, and aldesleukin
Drug: Fludarabine
50 mg/m2, IV(in the vein) on day 5 of each 25 day cycle
Drug: Cycolphosphamide
60 mg/kg/day X 2 days IV
Biological: Aldesleukin
72,000 IU/kg every 8 hours for a maximum of 15 doses

  Show Detailed Description


Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

    1. Metastatic or unresectable measurable cancers that express mesothelin. 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.
    2. 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.
    3. Greater than or equal to 18 years of age and less than or equal to 70 years of age.
    4. Willing to sign a durable power of attorney
    5. Able to understand and sign the Informed Consent Document
    6. Clinical performance status of ECOG 0 or 1.
    7. Life expectancy of greater than three months.
    8. 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 the cells are no longer detected in the blood.
    9. Serology:

      1. Seronegative for HIV antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are HIV seropositive can have decreased immunecompetence and thus be less responsive to the experimental treatment and more susceptible to its toxicities.)
      2. 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 HCV RNA negative.
    10. Women of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects of the treatment on the fetus.
    11. Hematology:

      1. Absolute neutrophil count greater than 1000/mm(3) without the support of filgrastim.
      2. WBC (> 3000/mm(3)).
      3. Platelet count greater than 100,000/mm(3).
      4. Hemoglobin greater than 8.0 g/dl.
    12. Chemistry:

      1. Serum ALT/AST less or equal to 2.5 times the upper limit of normal.
      2. Serum creatinine less than or equal to 1.6 mg/dl.
      3. 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.
    13. 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).


  1. Patients with sarcomatoid mesothelioma as mesothelin is not expressed in this type of mesothelioma.
  2. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
  3. Patients with known brain metastases.
  4. Patients receiving full dose anticoagulative therapy.
  5. 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.
  6. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  7. Concurrent 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).
  8. Patients with diabetic retinopathy.
  9. Concurrent Systemic steroid therapy.
  10. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  11. History of coronary revascularization or ischemic symptoms.
  12. In patients over 60 years of age, LVEF of less than 45%
  Contacts and Locations
Please refer to this study by its identifier: NCT01583686

Contact: June Kryk, R.N. (301) 451-1929
Contact: Steven A Rosenberg, M.D. (301) 496-4164

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center    866-820-4505   
Sponsors and Collaborators
Principal Investigator: Steven A Rosenberg, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ) Identifier: NCT01583686     History of Changes
Other Study ID Numbers: 120111, 12-C-0111
Study First Received: April 20, 2012
Last Updated: March 14, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Metastatic Cancer
Gene Therapy
Pancreatic Cancer

Additional relevant MeSH terms:
Lung Neoplasms
Neoplasm Metastasis
Neoplasms, Second Primary
Ovarian Neoplasms
Pancreatic Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms, Mesothelial
Neoplastic Processes
Pathologic Processes
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Digestive System Neoplasms
Digestive System Diseases
Pancreatic Diseases
Fludarabine processed this record on April 17, 2014