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Chemotherapy Followed By Autologous Natural Killer Cells and Aldesleukin in Treating Patients With Metastatic Melanoma or Kidney Cancer
This study has been completed.
First Received: July 19, 2006   Last Updated: April 18, 2009   History of Changes
Sponsored by: National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00354055
  Purpose

RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Aldesleukin may stimulate natural killer cells to kill tumor cells. Giving chemotherapy followed by autologous natural killer cells and aldesleukin may kill more tumor cells.

PURPOSE: This phase II trial is studying how well giving chemotherapy followed by autologous natural killer cells and aldesleukin works in treating patients with metastatic melanoma or kidney cancer.


Condition Intervention Phase
Kidney Cancer
Melanoma (Skin)
Biological: aldesleukin
Biological: therapeutic autologous lymphocytes
Drug: cyclophosphamide
Drug: fludarabine phosphate
Phase II

Study Type: Interventional
Study Design: Treatment, Open Label
Official Title: A Phase II Study in Metastatic Melanoma or Kidney Cancer Using Autologous Natural Killer Cells Plus Aldesleukin (IL-2) Following a Lymphodepleting Chemotherapy

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Tumor regression [ Designated as safety issue: No ]
  • Clinical response [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Natural killer (NK) cell repopulation in the immune system [ Designated as safety issue: No ]
  • Toxicity [ Designated as safety issue: Yes ]

Estimated Enrollment: 58
Study Start Date: May 2006
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the ability of the administration of autologous natural killer cells and aldesleukin after a nonmyeloablative lymphodepleting preparative regimen to mediate tumor regression in patients with metastatic melanoma or renal cell cancer.

Secondary

  • Determine the rate of repopulation of the natural killer cells in these patients.
  • Determine the toxic effects of this regimen in these patients.

OUTLINE: Patients are stratified according to disease (melanoma vs renal cell cancer).

  • Leukapheresis: Patients undergo apheresis to collect peripheral blood lymphocytes that are used for in vitro generation of autologous natural killer (NK) cell lymphocytes.
  • Nonmyeloablative preparative regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine phosphate IV over 15-30 minutes on days -5 to -1.
  • Autologous NK cell infusion: Patients receive autologous NK cells IV over 20-30 minutes on day 0.
  • Aldesleukin: Patients receive aldesleukin IV over 15 minutes every 8 hours beginning on day 0 and continuing for up to 5 days (maximum of 15 doses) during the first course and begin a second course 14 days later.

Patients who achieve partial or complete response and then develop progressive disease may receive 1 additional course of therapy as above.

After completion of study therapy, patients are followed periodically.

PROJECTED ACCRUAL: A total of 58 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed melanoma or renal cell cancer

    • Metastatic disease
  • Must have previously received high-dose aldesleukin and have progressive disease (i.e., no response) or recurrent disease
  • Measurable disease
  • No tumor-reactive T cells available for cell transfer therapy

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-1
  • Life expectancy ≥ 3 months
  • Platelet count > 100,000/mm^3
  • Absolute neutrophil count > 1,000/mm^3
  • Hemoglobin > 8.0 g/dL
  • ALT and AST < 3 times upper limit of normal
  • Creatinine ≤ 1.6 mg/dL
  • Bilirubin ≤ 2.0 mg/dL (3.0 mg/dL for patients with Gilbert's syndrome)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception prior to, during, and for up to 4 months after completion of study treatment
  • HIV negative
  • Hepatitis B surface antigen negative
  • Hepatitis C antibody negative
  • No abnormal stress cardiac test (e.g., stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test) in patients ≥ 50 years of age OR in patients with a history of EKG abnormalities, symptoms of cardiac ischemia, or arrhythmia
  • FEV_1 ≥ 60% predicted by pulmonary function test in patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction
  • No known toxicity during prior aldesleukin administration that would preclude redosing with aldesleukin, including any of the following:

    • Myocardial infarction
    • Mental status change requiring intubation
    • Bowel perforation
    • Renal failure requiring dialysis
  • No active systemic infection
  • No coagulation disorders
  • No autoimmune disease (e.g., autoimmune colitis or Crohn's disease)
  • No other major medical illness of the cardiovascular, respiratory, or immune system, as evidenced by any of the following:

    • Positive stress thallium or comparable test
    • Myocardial infarction
    • Cardiac arrhythmias
    • Obstructive or restrictive pulmonary disease

PRIOR CONCURRENT THERAPY:

  • At least 4 weeks since prior systemic therapy (6 weeks for nitrosoureas)
  • No concurrent steroid therapy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00354055

Locations
United States, Maryland
NCI - Surgery Branch
Bethesda, Maryland, United States, 20892-1201
Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office
Bethesda, Maryland, United States, 20892-1182
Sponsors and Collaborators
Investigators
Principal Investigator: Steven A. Rosenberg, MD, PhD NCI - Surgery Branch
  More Information

Additional Information:
No publications provided

Responsible Party: NCI - Surgery Branch ( Steven A. Rosenberg )
Study ID Numbers: CDR0000486918, NCI-06-C-0169, NCI-P6950
Study First Received: July 19, 2006
Last Updated: April 18, 2009
ClinicalTrials.gov Identifier: NCT00354055     History of Changes
Health Authority: United States: Food and Drug Administration

Keywords provided by National Cancer Institute (NCI):
recurrent melanoma
stage IV melanoma
stage IV renal cell cancer
stage IV melanoma

Study placed in the following topic categories:
Antimetabolites
Anti-Infective Agents
Urinary Tract Neoplasm
Immunologic Factors
Urogenital Neoplasms
Cyclophosphamide
Urologic Neoplasms
Melanoma
Renal Cancer
Anti-Retroviral Agents
Urologic Diseases
Kidney Neoplasms
Neoplasms, Germ Cell and Embryonal
Nevus, Pigmented
Neuroepithelioma
Kidney Diseases
Alkylating Agents
Kidney Cancer
Anti-HIV Agents
Fludarabine monophosphate
Antiviral Agents
Immunosuppressive Agents
Recurrence
Neuroendocrine Tumors
Carcinoma
Neuroectodermal Tumors
Aldesleukin
Carcinoma, Renal Cell
Antineoplastic Agents, Alkylating
Nevus

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Neoplasms, Nerve Tissue
Physiological Effects of Drugs
Urogenital Neoplasms
Cyclophosphamide
Urologic Neoplasms
Melanoma
Neoplasms by Site
Anti-Retroviral Agents
Urologic Diseases
Kidney Neoplasms
Therapeutic Uses
Neoplasms, Germ Cell and Embryonal
Nevi and Melanomas
Kidney Diseases
Alkylating Agents
Anti-HIV Agents
Neoplasms by Histologic Type
Fludarabine monophosphate
Antiviral Agents
Immunosuppressive Agents
Pharmacologic Actions
Carcinoma
Neuroendocrine Tumors
Neuroectodermal Tumors

ClinicalTrials.gov processed this record on September 11, 2009