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Laboratory-Treated Autologous Lymphocytes and Aldesleukin After Cyclophosphamide and Fludarabine in Treating Patients With Metastatic Melanoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00863330
Recruitment Status : Terminated (administrative decision- PI retired and treating physician left the institution)
First Posted : March 18, 2009
Results First Posted : December 17, 2014
Last Update Posted : January 6, 2015
Information provided by (Responsible Party):
Jackie Blundon, MS, CIP, Aurora Health Care

Brief Summary:

RATIONALE: Treating lymphocytes in the laboratory may help the lymphocytes kill more tumor cells when they are put back in the body. Aldesleukin may stimulate the lymphocytes to kill tumor cells. 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. Giving laboratory-treated lymphocytes and aldesleukin together with cyclophosphamide and fludarabine may kill more tumor cells.

PURPOSE: This phase II trial is studying how well laboratory-treated autologous lymphocytes and aldesleukin work when given after cyclophosphamide and fludarabine in treating patients with metastatic melanoma.

Condition or disease Intervention/treatment Phase
Melanoma (Skin) Biological: Tumor Infiltrating Lymphocytes (TIL) Phase 2

Detailed Description:



  • Determine the ability of treatment with short-term cultured autologous tumor-infiltrating lymphocytes (TIL) in combination with high-dose aldesleukin after a nonmyeloablative lymphocyte-depleting preparative regimen comprising cyclophosphamide and fludarabine phosphate to mediate tumor regression in patients with metastatic melanoma.
  • Determine the toxicity of this treatment regimen.


  • Determine the rate of repopulation of the young TIL cells.
  • Establish in vitro immunological correlates that predict in vivo persistence and clinical response.


  • Conditioning regimen: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine phosphate IV over 30 minutes on days -5 to -1.
  • Tumor-infiltrating lymphocyte (TIL) infusion and high-dose aldesleukin: Patients receive short-term cultured autologous TIL IV over 20-30 minutes on day 0. Patients also receive high-dose aldesleukin IV over 15 minutes every 8 hours on days 0-4.

Patients with stable disease, partial response, or recurrent disease after initial response may receive 1 additional course of treatment (as above) beginning 8 weeks after completion of aldesleukin.

Blood samples are collected at baseline, at 1 week and 1 month after TIL infusion, and then periodically thereafter for research studies. Samples are analyzed for differences in function and phenotype prior to and after TIL infusion. The immunological correlates of treatment are also evaluated using FACS, cytokine release assays, ELISPOT assays, flow cytometry, and PCR. TIL that are cryopreserved at the time of infusion are analyzed to determine cell phenotype and function; correlation of in vitro characteristics of the infused cells with in vivo antitumor activity; and the activity, specificity, and telomere length using flow FISH.

After completion of study treatment, patients are followed at 4-6 weeks, every 3 months for 1 year, every 6 months for 2 years, and then annually for 2 years.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma
Study Start Date : February 2009
Actual Primary Completion Date : July 2012
Actual Study Completion Date : July 2012

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arm Intervention/treatment
Experimental: Determine toxicity of treatment regimen. Biological: Tumor Infiltrating Lymphocytes (TIL)
Tumor harvest process tumor infiltrating lymphocytes. Non myeloblative chemotherapy consisting of cyclophosphamide and fludarabine. Infusion of TIL cells followed by high dose IL-2.

Primary Outcome Measures :
  1. Primary Objective [ Time Frame: 4-6 weeks after completion of TIL ]
    Determine the ability of autologous cells infused with minimal in vitro culture in conjunction with high dose interleukin -2 (IL-2) following non-myeloablative lymphodepleting preparative regimen to mediate tumor regression in patients with metastatic melanoma.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Diagnosis of metastatic melanoma
  • Refractory to standard treatment including high-dose aldesleukin (IL-2), unless previously ineligible for or refused IL-2
  • Measurable disease with ≥ 1 lesion that is resectable for tumor-infiltrating lymphocyte generation
  • Patients with ≥ 1 brain metastases < 1 cm each, or 1-2 brain metastases > 1 cm are eligible provided they have been treated and stable for ≥ 3 months


  • ECOG performance status 0-1
  • Life expectancy > 3 months
  • ANC > 1,000/mm^3 (without filgrastim support)
  • WBC > 3,000/mm^3
  • Hemoglobin > 8.0 g/dL
  • Platelet count > 100,000/mm^3
  • Serum ALT/AST < 3 times upper limit of normal
  • Total bilirubin ≤ 2 mg/dL (< 3 mg/dL in patients with Gilbert's syndrome)
  • Serum creatinine ≤ 1.6 mg/dL
  • LVEF > 45% in patients meeting the following criteria:

    • Clinically significant atrial and/or ventricular arrhythmias, including, but not limited to, atrial fibrillation, ventricular tachycardia, or second- or third-degree heart block
    • At least 60 years of age
  • FEV_1 > 60% in patients meeting the following criteria:

    • Prolonged history of cigarette smoking
    • Symptoms of respiratory dysfunction
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for 4 months after completion of study treatment
  • No HIV or hepatitis B or C positivity
  • No form of primary immunodeficiency (e.g., severe combined immunodeficiency disease or AIDS)
  • No opportunistic infections
  • No active systemic infections
  • No history of severe immediate hypersensitivity reaction to any of the agents used in this study
  • No coagulation disorders
  • No myocardial infarction, cardiac arrhythmias, or positive stress thallium or comparable test
  • No history of coronary revascularization or ischemic symptoms
  • No obstructive or restrictive pulmonary disease
  • No other active major medical illness of the cardiovascular, respiratory, or immune system


  • See Disease Characteristics
  • Recovered from prior therapy (alopecia or vitiligo allowed)
  • At least 6 weeks since prior ipilimumab

    • Must have normal colonoscopy with normal colonic biopsies
  • At least 4 weeks since prior systemic therapy
  • Minor surgical procedures within the past 3 weeks allowed provided all toxicities have recovered to ≤ grade 1
  • No concurrent systemic steroids
  • No other concurrent experimental agents

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00863330

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United States, Wisconsin
Aurora St. Luke's Medical Center
Milwaukee, Wisconsin, United States, 53215
Sponsors and Collaborators
Aurora Health Care
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Principal Investigator: John P. Hanson, MD St. Luke's Medical Center
Principal Investigator: Jonathan S. Treisman, MD St. Luke's Medical Center
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Responsible Party: Jackie Blundon, MS, CIP, Research Regulatory Specialist, Aurora Health Care Identifier: NCT00863330    
Other Study ID Numbers: CDR0000636885
First Posted: March 18, 2009    Key Record Dates
Results First Posted: December 17, 2014
Last Update Posted: January 6, 2015
Last Verified: December 2014
Keywords provided by Jackie Blundon, MS, CIP, Aurora Health Care:
stage IV melanoma
recurrent melanoma
Additional relevant MeSH terms:
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Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms, Nerve Tissue
Nevi and Melanomas