Cultured White Cells Plus Interleukin-2 to Treat Advanced Kidney Cancer

NCT00091611 | Terminated Phase 1

• 2 other identifiers: 04027704-C-0277
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Some patients with advanced kidney cancer have immune cells that can recognize and kill their cancer, but the cells are not active enough or numerous enough to accomplish this on their own.
• In recent studies of patients with advanced melanoma, some patients given special tumor-fighting cells (cells taken from the patient's tumor cells and grown in the laboratory) showed some anti-tumor response. Objectives:
• To determine whether special tumor-fighting cells taken from the patient's blood or tumor and grown in the laboratory can cause tumors in patients with kidney cancer to shrink when they are given back to the patient along with interleukin-2. Eligibility: Patients 18 years of age or older with advanced kidney cancer. Design:
• Up to 29 patients will be treated in this study.
• Patients undergo tumor biopsy to collect tumor cells for creating special tumor-fighting cells for later infusion.
• Patients undergo apheresis to collect stem cells for later re-infusion. For apheresis, whole blood is collected through a needle in an arm vein and circulated through a cell-separating machine where the stem cells are extracted. The rest of the blood is returned through the same needle or a needle in the other arm.
• Before receiving the treated white cells, patients are given two drugs to suppress the immune system so the treated cells can work without interference from immune system cells. They are given cyclophosphamide over 2 days through a catheter (plastic tube inserted into a vein in the arm or neck) and fludarabine through the catheter over 15-30 minutes for the next 5 days.
• The day after the last dose of fludarabine, the tumor-fighting cells are infused through a vein over 10-20 minutes.
• Following the cell infusion, patients start treatment with high-dose interleukin-2 every 8 hours for a maximum of 12 doses.
• Patients are evaluated with x-ray studies about 1 month after receiving the cells and interleukin 2 (IL-2) to look for tumor response to treatment. Those who show significant improvement continue to receive treatment until the treated cells are used up or the patient no longer benefits or develops unacceptable side effects.

Conditions

Kidney Neoplasms

Keywords

Clinical Response; Intravenous; Intra-Arterial; Lymphodepletion; Traffic of Cells; T-Cell Transfer; Renal Cell Carcinoma; Metastatic Renal Cell Cancer

Outcome Measures

Primary Outcomes (1)

• Determine whether Adoptive Lymphocyte Transfer in Conjunction with Preparative Lympho-depletion Chemotherapy and Interleukin-2 (IL-2) May result in Clinical Tumor Regression in Metastatic Renal Cancer

Interventions

IL-2 (interleukin-2) DRUG

OKT3 DRUG

Cyclophosphamide DRUG

Fludarabine DRUG

Mesna DRUG

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have metastatic renal cell cancer.
• age greater than or equal to 18 years.
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1 at entry to the trial.
• Life expectancy of greater than three months.
• Seronegative for human immunodeficiency virus (HIV) antibody. (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who are human immunodeficiency virus (HIV) seropositive can have decreased immune competence and can thus be less responsive to the experimental treatment and more susceptible to it's toxicities.)
• Seronegative for hepatitis B antigen.
• Seropositive for Epstein-Barr Virus (EBV).
• Patients with electrocardiogram (EKG) abnormalities, symptoms of cardiac ischemia or arrythmias or age greater than 50 years must have a normal stress cardiac test (stress thallium, stress multi-gated acquisition scan (MUGA), dobutamine echocardiogram or other stress test).
• Patients who have a recent prolonged history of cigarette smoking or symptoms of respiratory dysfunction must have pulmonary function testing with an forced expiratory volume in 1 second (FEV(1)) greater than 60% predicted.

You may not qualify if:

• Active systemic infections, coagulation disorders, contra-indications to receiving interleukin-2 (IL-2) or major medical illnesses of the cardiovascular, respiratory or immune system.
• Patients must have measurable metastatic renal cell cancer and have tumor progression after therapy with interleukin-2 (IL-2).
• Clinical performance status of Eastern Cooperative Oncology Group (ECOG) 0, 1 at entry to the treatment phase of this trial.
• Platelet count greater than 100,000/mm\^3.
• Serum alanine aminotransferase (ALT)/aspartate aminotransferase (AST) less than three times the upper limit of normal.
• Serum creatinine less than or equal to 1.6 mg/dl.
• Total bilirubin less than or equal to 1.6 mg/dl or direct bilirubin less than or equal to 0.5 mg/dl.
• Life expectancy of greater than three months.
• At the time of T-cell transfer, the patient must have a T-cell population which has met the attached Certificate of Analysis for tumor recognition and safety testing.
• Any patient receiving interleukin-2 (IL-2) must sign a durable power of attorney.
• Male and Female patients must be willing to practice contraception during the treatment phase of this study..
• Patients with asymptomatic brain metastases may be considered eligible.
• Potentially effective therapy for renal cell cancer (RCC) within four weeks of the time the patient receives T-cell transfer (with the exception of local irradiation to non-evaluated sites).
• Requirement for steroid therapy.
• Active systemic infections, coagulation disorders, contra-indications to receiving interleukin-2 (IL-2) or major medical illnesses or the cardiovascular, respiratory or immune system.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Cancer Institute (NCI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (1)

• Rosenberg SA, Zhai Y, Yang JC, Schwartzentruber DJ, Hwu P, Marincola FM, Topalian SL, Restifo NP, Seipp CA, Einhorn JH, Roberts B, White DE. Immunizing patients with metastatic melanoma using recombinant adenoviruses encoding MART-1 or gp100 melanoma antigens. J Natl Cancer Inst. 1998 Dec 16;90(24):1894-900. doi: 10.1093/jnci/90.24.1894.

  PMID: 9862627 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Kidney Neoplasms; Carcinoma, Renal Cell

Interventions

Interleukin-2; Muromonab-CD3; Cyclophosphamide; fludarabine; Mesna

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Interleukins; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Lymphokines; Proteins; Biological Factors; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Immunoglobulin G; Immunoglobulin Isotypes; Serum Globulins; Globulins; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Sulfhydryl Compounds; Sulfur Compounds; Sulfonic Acids; Sulfur Acids

Study Officials

• James Yang, M.D.

  National Cancer Institute, National Institutes of Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2004
• First Posted: September 13, 2004
• Study Start: September 1, 2004
• Primary Completion: April 1, 2006
• Study Completion: March 1, 2008
• Last Updated: October 26, 2012

Record last verified: 2012-10

Locations

US (1)