Treating Metastatic Cancer With Anti-VEGFR2 Gene Engineered CD8+ Lymphocytes

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01218867
First received: October 8, 2010
Last updated: July 24, 2014
Last verified: April 2014
  Purpose

Background:

- One experimental treatment for certain types of cancer is cell therapy, which involves collecting lymphocytes (white blood cells) from an individual, growing the cells in the laboratory in large numbers, and then modifying the cells with a gene (anti-VEGFR2 gene) that prevents the growth of blood vessels that supply blood to tumors. Because this treatment is experimental, researchers are interested in determining the side effects and overall effectiveness of cell therapy using white blood cells modified with the anti-VEGFR2 gene as a treatment for aggressive cancer that has not responded to standard therapy.

Objectives:

- To determine the safety and effectiveness of cell therapy using anti-VEGFR2 gene modified tumor white blood cells to treat recurrent or relapsed cancer.

Eligibility:

- Individuals greater than or equal to 18 years of age and less than or equal to 66 years of age who have been diagnosed with metastatic cancer that has not responded to or has relapsed after standard treatment.

Design:

  • Participants will be screened with a medical history, physical examination, blood and urine tests, and imaging studies.
  • Cells for treatment will be collected during leukapheresis, which will separate the white blood cells and return the rest of the blood to the participant.
  • Prior to the start of cell therapy, participants will have imaging procedures, heart and lung function tests, eye examinations, and blood and urine tests.
  • For 7 days before the cell infusion, participants will be admitted for inpatient chemotherapy with cyclophosphamide and fludarabine to suppress the immune system in preparation for the cell therapy.
  • Participants will receive the modified white blood cells as an infusion 1 to 4 days after the last dose of chemotherapy. The day after the infusion, participants will receive a dose of filgrastim to stimulate blood cell growth, and will begin to receive IL-2 (a drug that will help keep the modified white blood cells active) up to every 8 hours for 5 days.
  • Participants will remain as inpatients for at least 5 to 10 days after the last IL-2 to recover from the treatment, and will be followed regularly after the treatment to study side effects and general effectiveness.
  • Participants who initially respond to treatment but have a relapse may have one additional treatment using the same procedure.

Condition Intervention Phase
Metastatic Cancer
Metastatic Melanoma
Renal Cancer
Colorectal Cancer
Ovarian Cancer
Lung Cancer
Genetic: Anti-VEGFR2 CAR CD8 plus PBL
Drug: Cyclophosphamide
Drug: Aldesleukin
Drug: Fludarabine
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-VEGFR2 Gene Engineered CD8+ Lymphocytes

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Determine whether objective responses can be mediated in patients treated with the anti-VEGFR2 CAR engineered CD8+ PBL and low dose aldesleukin [ Time Frame: 6 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 118
Study Start Date: October 2010
Estimated Study Completion Date: October 2018
Estimated Primary Completion Date: October 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single Arm
Patients will receive cells plus low dosealdesleukin - adoptic cell therapy
Genetic: Anti-VEGFR2 CAR CD8 plus PBL
Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophospamide and fludarabine followed by the administration of anti-VEGFR CAR CD8+ PBL and low dose aldesleukin. On day 0, cells will be infused in the Patient Care Unit over 20-30 minutes (Phase 1: 10e6- 3x10e10 cells and Phase 2: maximum tolerated dose of cells from Phase 1)
Drug: Cyclophosphamide
Cyclophosphamide 60 mg/kg/day X 2 days IV in 250 ml D5W with mesna 15 mg/kg/day X 2 days over 1 hr
Drug: Aldesleukin
Aldesleukin (based on total body weight) will be administered at a dose of 72,000 IU/kg as an intravenous bolus over a 15 minute period approximately every eight hours (+/- 1 hour) beginning within 24 hours of the cell infusion and continuing for up to 5 days (maximum 15 doses)
Drug: Fludarabine
Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Metastatic cancer with evaluable disease.
    2. Patients must have previously received at least one systemic standard care (or effective salvage chemotherapy regimens) for metastatic 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 treatment.
    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 immune-competence 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. 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.
    11. 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.
    12. 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).
    13. More than 4 weeks must have elapsed since an surgical procedure at the time the patient receives the preparative regimen due to the inhibition of wound healing observed with VEGFR targeting angiogenesis inhibitors.

EXCLUSION CRITERIA:

  1. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
  2. Patients with known brain metastases.
  3. Patients receiving full dose anticoagulative therapy.
  4. 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.
  5. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  6. 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).
  7. Patients with diabetic retinopathy.
  8. Concurrent Systemic steroid therapy.
  9. History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  10. History of coronary revascularization or ischemic symptoms.
  11. In patients

Documented FEV1 less than or equal to 45% predicted tested in patients with:

  1. History of ischemic heart disease, chest pain, or clinically significant atrial and/or ventricular arrhythmias including but not limited to: atrial fibrillation, ventricular tachycardia, second or third degree heart block.
  2. Age greater than or equal to 60 years old.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01218867

Contacts
Contact: June Kryk, R.N. (301) 451-1929 ncisbirc@mail.nih.gov
Contact: Steven A Rosenberg, M.D. (301) 496-4164 sar@mail.nih.gov

Locations
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    ncisbirc@mail.nih.gov   
Sponsors and Collaborators
Investigators
Principal Investigator: Steven A Rosenberg, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01218867     History of Changes
Other Study ID Numbers: 110013, 11-C-0013
Study First Received: October 8, 2010
Last Updated: July 24, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Clinical Response
Metastatic Cancer
Immunotherapy
Adoptive Cell Therapy
Metastatic Melanoma

Additional relevant MeSH terms:
Carcinoma, Renal Cell
Kidney Neoplasms
Colorectal Neoplasms
Lung Neoplasms
Melanoma
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Ovarian Neoplasms
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on August 20, 2014