Trial record 1 of 1 for:    08-C-0121
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Chemotherapy Followed by ESO-1 Lymphocytes and Aldesleukin to Treat Metastatic Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT00670748
First received: May 1, 2008
Last updated: September 9, 2014
Last verified: August 2014
  Purpose

Background:

-This study uses an experimental cancer treatment that uses the patient s own lymphocytes (type of white blood cell), which are specially selected and genetically modified to target and destroy their tumor.

Objectives:

-To test the safety of the treatment and determine if it can cause the patient s tumor to shrink.

Eligibility:

  • Patients greater than 18 years and less than or equal to 66 years of age whose cancer has spread beyond the original site and does not respond to standard treatment.
  • Patients have tissue type HLA-A*0201.
  • Patients cancer cells have the ESO-1 gene.

Design:

  • Workup: Patients have scans, x-rays, laboratory tests, and other tests as needed.
  • Patients have leukapheresis to collect cells for laboratory treatment and later reinfusion. For this procedure, whole blood is collected thorough a tube in a vein, the desired cells are extracted from the blood, and the rest of the blood is returned to the patient.
  • Chemotherapy: Patients have low-dose chemotherapy for 1 week to prepare the immune system to receive the treated lymphocytes.
  • Cell infusion and aldesleukin (IL-2) treatment: Patients receive the lymphocytes by a 30-minute infusion through a vein. Starting within 24 hours of the infusion, they receive high-dose aldesleukin infusions every 8 hours for up to 5 days (maximum15 doses).
  • Recovery: Patients rest for 1 to 2 weeks to recover from the effects of chemotherapy and aldesleukin.
  • Tumor biopsy: Patients may be asked to undergo a biopsy (surgical removal of a small piece of tumor) after treatment to look at the effects of treatment on the immune cells in the tumor.
  • Follow-up: After treatment is completed, patients return to the clinic once a month for several months for physical examinations, a review of side effects, laboratory tests and scans. They may undergo leukapheresis at some visits to look at the effect of treatment on the immune system and check the viability of the infused cells. Patients then return to the NIH clinic once a year for 5 years and then complete a follow-up questionnaire for another 10 years.
  • Retreatment: Patients whose tumor shrinks or disappears following treatment and then recurs may receive one additional treatment, using the same regimen of chemotherapy, lymphocyte infusion and IL-2 treatment.

Condition Intervention Phase
Metastatic Melanoma
Metastatic Renal Cell Cancer
Metastatic Cancer
Biological: Anti-NY ESO-1 TCR PBL
Drug: aldesleukin
Drug: cyclophosphaide
Drug: fludarabine phosphate
Biological: ALVAC NY ESO-1 vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study of Metastatic Cancer That Expresses NY-ESO-1 Using Lymphodepleting Conditioning Followed by Infusion of Anti-NY ESO-1 TCR-Gene Engineered Lymphocytes

Resource links provided by NLM:


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

Primary Outcome Measures:
  • In cohorts 1 and 2, determine if the administration of anti-ESO TCR engineered PBL and aldesleukin following preparative chemotherapy regimen results in objective tumor regression [ Time Frame: Approximately 3 years ] [ Designated as safety issue: Yes ]
  • In cohorts 3 and 4, determine if the administration of anti-ESO TCR-engineered PBL,aldesleukin and ALVAC ESO-1 vaccine following preparative chemotherapy regimen results in objective tumor regression [ Time Frame: Approximately 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 45
Study Start Date: April 2008
Estimated Study Completion Date: September 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Patients with melanoma or renal cell cancer (RCC) will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by anti-NY ESO-1 TCR PBL and high dose aldesleukin
Biological: Anti-NY ESO-1 TCR PBL
Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of anti-NY ESO-1 TCR PBL and high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Patient Care Unit over 20-30 minutes.
Drug: aldesleukin
Aldeskeukin 720,000 IU/kg IV (based on total body weight)over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days(maximum of 15 doses)
Drug: cyclophosphaide
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: fludarabine phosphate
Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Experimental: Cohort 2
Patients with cancers other than melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by anti-NY ESO-1 TCR PBL and high dose aldesleukin
Biological: Anti-NY ESO-1 TCR PBL
Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of anti-NY ESO-1 TCR PBL and high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Patient Care Unit over 20-30 minutes.
Drug: aldesleukin
Aldeskeukin 720,000 IU/kg IV (based on total body weight)over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days(maximum of 15 doses)
Drug: cyclophosphaide
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: fludarabine phosphate
Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Experimental: Cohort 3
Patients with melanoma or RCC will receive non-myeloablative lymphodepleting regimen ofcyclophosphamide and fludarabine followed by ALVAC NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
Biological: Anti-NY ESO-1 TCR PBL
Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of anti-NY ESO-1 TCR PBL and high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Patient Care Unit over 20-30 minutes.
Drug: aldesleukin
Aldeskeukin 720,000 IU/kg IV (based on total body weight)over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days(maximum of 15 doses)
Drug: cyclophosphaide
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: fludarabine phosphate
Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Biological: ALVAC NY ESO-1 vaccine
Approximately two hours prior to cell infusion, patients will receive 0.5 mL containing a target dose of 10e7 CCID50 (with a range of approximately 10e6.4 to 10e7.9 / mL) of the ESO-1 ALVAC virus S.C. in each extremity (total of 4 x 10e7 CCID50/2 mL.
Experimental: Cohort 4
Patients with cancers other than melanoma or RCC will receive non-myeloablative lymphodepleting regimen of cyclophosphamide and fludarabine followed by ALVAC NY-ESO-1 vaccine, anti-NY ESO-1 TCR PBL and high dose aldesleukin
Biological: Anti-NY ESO-1 TCR PBL
Patients will receive non-myeloablative lymphodepleting preparative regimen consisting of cyclophosphamide and fludarabine followed by the administration of anti-NY ESO-1 TCR PBL and high dose aldesleukin. On day 0,cells (1x10e8 to 1x10e11)will be infused intravenously on the Patient Care Unit over 20-30 minutes.
Drug: aldesleukin
Aldeskeukin 720,000 IU/kg IV (based on total body weight)over 15 minutes every eight hours (+/- 1 hour) beginning within 24 hours of cell infusion and continuing for up to 5 days(maximum of 15 doses)
Drug: cyclophosphaide
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: fludarabine phosphate
Fludarabine 25 mg/m2/day IVPB daily over 30 minutes for 5 days.
Biological: ALVAC NY ESO-1 vaccine
Approximately two hours prior to cell infusion, patients will receive 0.5 mL containing a target dose of 10e7 CCID50 (with a range of approximately 10e6.4 to 10e7.9 / mL) of the ESO-1 ALVAC virus S.C. in each extremity (total of 4 x 10e7 CCID50/2 mL.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 66 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:
  • Metastatic cancer that expresses ESO as assessed by one of the following methods: RT-PCR on tumor tissue, or by immunohistochemistry of resected tissue, or serum antibody reactive with ESO. Metastatic cancer diagnosis will be confirmed by the Laboratory of Pathology at the NCI.
  • Patients with histologies other than metastatic melanoma, must have previously received 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.
  • Greater than or equal to 18 years of age. and less than or equal to 66 years of age.
  • Willing to sign a durable power of attorney.
  • Able to understand and sign the Informed Consent Document.
  • Clinical performance status of ECOG 0 or 1.
  • Life expectancy of greater than three months.
  • Patients of both genders must be willing to practice birth control for four months after receiving the preparative regimen.
  • Patients must be HLA-A*0201 positive
  • Serology:

    • 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.)
    • Seronegative for hepatitis B antigen and hepatitis C antibody unless antigen negative. If hepatitis C antibody test is positive, then patients must be tested for the presense of antigen by RT-PCR and be HCV RNA negative.
  • Hematology:

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

    • Serum ALT/AST less or equal to 2.5 times the upper limit of normal.
    • Serum creatinine less than or equal to 1.6 mg/dl.
    • 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.
  • 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).
  • Six weeks must have elapsed since prior ipilimumabtherapy to allow antibody levels to decline.
  • Patients who have previously received ipilimumab or ticilimumab anti-PD1 or anti-PD-L1 antibodies, and have documented GI toxicity must have a normal colonoscopy with normal colonic biopsies.

EXCLUSION CRITERIA:

  • Prior vaccination with an ALVAC containing vaccine for patients who will receive the ALVAC ESO-1 vaccine (cohorts 3 or 4).
  • Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the preparative chemotherapy on the fetus or infant.
  • 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.
  • Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  • 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).
  • Concurrent Systemic steroid therapy.
  • Known systemic hypersensitivity to any of the vaccine components, including egg products or Neomycin for patients who will receive the ALVAC ESO-1 vaccine (cohorts 3 or 4).
  • History of severe immediate hypersensitivity reaction to any of the agents used in this study.
  • History of coronary revascularization or ischemic symptoms.
  • Any patient known to have an LVEF less than or equal to 45 percent.
  • Documented LVEF of less than or equal to 45 percent tested in patients with:

    • 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.
    • Age greater than or equal to 60 years old.
  • Documented FEV1 less than or equal to 60 percent predicted tested in patients with:

    • A prolonged history of cigarette smoking (20 pk/year of smoking within the past 2 years).
    • Symptoms of respiratory dysfunction
  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: NCT00670748

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
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: NCT00670748     History of Changes
Other Study ID Numbers: 080121, 08-C-0121
Study First Received: May 1, 2008
Last Updated: September 9, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Metastatic Cancer
Gene Therapy
Immunotherapy
Tumor Regression
Metastatic Melanoma
Metastatic Renal Cell Cancer

Additional relevant MeSH terms:
Neoplasm Metastasis
Neoplasms
Neoplasms, Second Primary
Melanoma
Carcinoma, Renal Cell
Neoplastic Processes
Pathologic Processes
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases
Cyclophosphamide
Fludarabine phosphate
Fludarabine
Aldesleukin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on September 16, 2014