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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

Tracking Information
First Submitted Date  ICMJE March 17, 2009
First Posted Date  ICMJE March 18, 2009
Results First Submitted Date  ICMJE December 3, 2014
Results First Posted Date  ICMJE December 17, 2014
Last Update Posted Date January 6, 2015
Study Start Date  ICMJE February 2009
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 3, 2012)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 17, 2009)
  • Tumor regression
  • Toxicity
Change History Complete list of historical versions of study NCT00863330 on Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: March 17, 2009)
  • Rate of repopulation of young tumor-infiltrating lymphocytes
  • In vitro immunological correlates that predict in vivo persistence and clinical response
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Laboratory-Treated Autologous Lymphocytes and Aldesleukin After Cyclophosphamide and Fludarabine in Treating Patients With Metastatic Melanoma
Official Title  ICMJE A Phase II Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Non-Myeloablative Lymphocyte Depleting Chemotherapy Regimen in Metastatic Melanoma
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Melanoma (Skin)
Intervention  ICMJE 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.
Study Arms  ICMJE Experimental: Determine toxicity of treatment regimen.
Intervention: Biological: Tumor Infiltrating Lymphocytes (TIL)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: December 15, 2014)
Original Estimated Enrollment  ICMJE
 (submitted: March 17, 2009)
Actual Study Completion Date  ICMJE July 2012
Actual Primary Completion Date July 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE


  • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00863330
Other Study ID Numbers  ICMJE CDR0000636885
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Jackie Blundon, MS, CIP, Aurora Health Care
Study Sponsor  ICMJE Aurora Health Care
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: John P. Hanson, MD St. Luke's Medical Center
Principal Investigator: Jonathan S. Treisman, MD St. Luke's Medical Center
PRS Account Aurora Health Care
Verification Date December 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP