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Therapeutic Autologous Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Stage IV 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.
 
ClinicalTrials.gov Identifier: NCT00438984
Recruitment Status : Completed
First Posted : February 22, 2007
Last Update Posted : March 16, 2012
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by:
Fred Hutchinson Cancer Research Center

Tracking Information
First Submitted Date  ICMJE February 20, 2007
First Posted Date  ICMJE February 22, 2007
Last Update Posted Date March 16, 2012
Study Start Date  ICMJE December 2006
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 24, 2011)
  • The identification of a CY/IL-2 regimen that is considered to be safe [ Time Frame: Baseline, 4 weeks and 8 weeks ]
  • The identification of a CY/IL-2 regimen (among those considered safe) which yields the greatest effect on the duration of in vivo persistence of adoptively transferred CTL clones [ Time Frame: Baseline, 4 weeks and 8 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 20, 2007)
  • Safety
  • Duration of in vivo persistence of adoptively transferred cytotoxic T-lymphocyte clones
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2007)
Response
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Therapeutic Autologous Lymphocytes, Cyclophosphamide, and Aldesleukin in Treating Patients With Stage IV Melanoma
Official Title  ICMJE Phase I Study To Evaluate Cellular Adoptive Immunotherapy Using Autologous CD8+ Antigen-Specific T Cell Clones Following Cyclophosphamide Conditioning For Patients With Metastatic Melanoma
Brief Summary

RATIONALE: Biological therapies, such as therapeutic autologous lymphocytes, may stimulate the immune system in different ways and stop tumor cells from growing. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Cyclophosphamide may also stimulate the immune system in different ways and stop tumor cells from growing. Aldesleukin may stimulate white blood cells to kill tumor cells. Giving therapeutic autologous lymphocytes together with cyclophosphamide and aldesleukin may be an effective treatment for melanoma.

PURPOSE: This phase I trial is studying the side effects of giving therapeutic autologous lymphocytes together with cyclophosphamide and aldesleukin in treating patients with stage IV melanoma

Detailed Description

PRIMARY OBJECTIVES:

I. To assess the safety and toxicity of cellular adoptive immunotherapy in melanoma patients receiving autologous CD8+ antigen-specific T cell clones following cyclophosphamide conditioning and post-infusion IL-2.

II. To assess the duration of in vivo persistence of adoptively transferred CD8+ T cell clones.

SECONDARY OBJECTIVES:

I. Evaluate the antitumor effect of adoptively transferred CD8+ antigenspecific cytotoxic t lymphocytes (CTL) clones following cyclophosphamide conditioning and post-infusion IL-2.

OUTLINE:

Patients are assigned 1of 2 treatment cohorts.

All patients receive high-dose cyclophosphamide intravenously (IV) on days -3 and -2 and autologous antigen-specific cytotoxic CD8+ T lymphocyte clones IV over 30-60 minutes on day 0.

COHORT I: Beginning within 6 hours of T cell infusion, patients receive low-dose aldesleukin subcutaneously (SC) twice daily on days 0-14.

COHORT II: Beginning within 6 hours of T cell infusion, patients receive high-dose aldesleukin IV 3 times daily on days 0-5.

Treatment continues in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 4 weeks, 8 weeks, and every 3 months thereafter for up to 1 year.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Recurrent Melanoma
  • Stage IV Melanoma
Intervention  ICMJE
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Biological: therapeutic autologous lymphocytes
    Given IV
    Other Names:
    • AL
    • Autologous Lymphocytes
    • autologous T cells
  • Biological: aldesleukin
    Given IV or SC
    Other Names:
    • IL-2
    • Proleukin
    • recombinant human interleukin-2
    • recombinant interleukin-2
  • Other: immunohistochemistry staining method
    Correlative studies
    Other Name: immunohistochemistry
  • Procedure: biopsy
    Optional correlative studies
    Other Name: biopsies
  • Other: laboratory biomarker analysis
    Correlative studies
  • Other: immunologic technique
    Correlative studies
    Other Names:
    • immunological laboratory methods
    • laboratory methods, immunological
  • Genetic: polymerase chain reaction
    Correlative studies
    Other Name: PCR
Study Arms  ICMJE Experimental: Treatment (chemotherapy, immunosuppressive, lymphocytes)

All patients receive high-dose cyclophosphamide IV on days -3 and -2 and autologous antigen-specific cytotoxic CD8+ T-lymphocyte clones IV over 30-60 minutes on day 0.

COHORT I: Beginning within 6 hours of T cell infusion, patients receive low-dose aldesleukin SC twice daily on days 0-14.

COHORT II: Beginning within 6 hours of T cell infusion, patients receive high-dose aldesleukin IV 3 times daily on days 0-5.

Interventions:
  • Drug: cyclophosphamide
  • Biological: therapeutic autologous lymphocytes
  • Biological: aldesleukin
  • Other: immunohistochemistry staining method
  • Procedure: biopsy
  • Other: laboratory biomarker analysis
  • Other: immunologic technique
  • Genetic: polymerase chain reaction
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 14, 2012)
11
Original Enrollment  ICMJE
 (submitted: February 20, 2007)
12
Actual Study Completion Date  ICMJE February 2012
Actual Primary Completion Date January 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histopathological documentation of melanoma concurrent with the diagnosis of metastatic disease
  • Expression of HLA-A2, B44, or A3 as determined by Fred Hutchinson Cancer Research Center (FHCRC) human leukocyte antigen (HLA) typing lab
  • Zubrod performance status of 0-1
  • Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging (X-ray, CT scan)
  • Normal cardiac stress test within 182 days prior to enrollment is required of all patients over 50 years old or those with an abnormal electrocardiogram (ECG), any history of cardiac disease, a family history of cardiac disease, hypercholesterolemia or hypertension
  • FOR LEUKAPHERESIS:
  • Pulse > 45 or < 120
  • Weight >= 45 kg
  • White blood cell count (WBC) >= 3,000
  • Temperature =< 38C (=< 100.4 F)
  • Hematocrit (HCT) >= 30%
  • Platelets >= 100,000
  • FOR T CELL INFUSION: Patients must be willing and able to discontinue the use of all anti-hypertensive medications 24 hours prior to and during IL-2 therapy

Exclusion Criteria:

  • Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception or abstinence; women of childbearing potential must have a negative pregnancy test within two weeks prior to entry
  • Serum creatinine > 1.6 mg/dL or Creatinine clearance < 75 ml/min
  • Serum glutamic oxaloacetic transaminase (SGOT) > 150 IU or > 3x upper limit of normal
  • Bilirubin > 1.6 mg/dL
  • Prothrombin time > 1.5 x control
  • Clinically significant pulmonary dysfunction, as determined by medical history and physical exam; patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 2.0 L or carbon monoxide diffusing capacity (DLco) (corr for Hgb) < 75% will be excluded
  • Significant cardiovascular abnormalities as defined by any one of the following:
  • Congestive heart failure;
  • Clinically significant hypotension;
  • Symptoms of coronary artery disease;
  • Presence of cardiac arrhythmias on electrocardiograph (EKG) requiring drug therapy;
  • Ejection fraction < 50 % (echocardiogram or multi gated acquisition scan [MUGA])
  • Symptomatic central nervous system metastases greater than 1 cm at the time of therapy; patients with 1-2 asymptomatic, less than 1 cm brain/central nervous system (CNS) metastases without significant edema may be considered for treatment; if sub-centimeter CNS lesions are noted at study entry, than a repeat imaging will be performed if more than 3 weeks have elapsed from the last scan; patients will not be treated if CNS lesions are > 1 cm or if patient is symptomatic from brain metastasis
  • Patients with active infections or oral temperature > 38.2 C within 72 hours of study entry or systemic infection requiring chronic maintenance or suppressive therapy
  • Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy; (patients with bulky disease may undergo cytoreductive chemotherapy but treatment will be discontinued at least 3 weeks prior to T cell therapy)
  • Clinically significant autoimmune disorders or conditions of immunosuppression; patients with acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV)-1 associated complex or known to HIV antibody seropositive or known to be recently polymerase chain reaction (PCR)+ for hepatitis are not eligible for this study; virology testing will be done within 6 months of T cell infusion; the severely depressed immune system found in these infected patients and the possibility of premature death would compromise study objectives
  • FOR T CELL INFUSION: Patients with active infections or oral temperature > 38.2 C within 72 hours of study entry or systemic infection requiring chronic maintenance or suppressive therapy
  • FOR T CELL INFUSION: Chemotherapeutic agents (standard or experimental), radiation therapy, or other immunosuppressive therapies less than 3 weeks prior to T cell therapy
  • FOR T CELL INFUSION: Current treatment with steroids
  • FOR T CELL INFUSION: Patients must not be receiving any other experimental drugs within 3 weeks of the initiation of the protocol and must have recovered from all side effects of such therapy
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (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 NCT00438984
Other Study ID Numbers  ICMJE 2140.00
NCI-2010-01280 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
R21CA128283 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yee, Cassian, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Study Sponsor  ICMJE Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Cassian Yee Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
PRS Account Fred Hutchinson Cancer Research Center
Verification Date March 2012

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