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Phase I Study To Evaluate Cellular Adoptive Immunotherapy Using Autologous IL-21 Modulated CD8+ Antigen-Specific T Cells For Patients With Metastatic Melanoma

Phase 1
18 Years
75 Years
Not Enrolling
Stage IV Melanoma

Thank you

Trial Information

Phase I Study To Evaluate Cellular Adoptive Immunotherapy Using Autologous IL-21 Modulated CD8+ Antigen-Specific T Cells For Patients With Metastatic Melanoma


I. Assess the safety and toxicity of adoptively transferred interleukin (IL)-21 modulated
cytotoxic T-lymphocyte (CTL) targeting a melanoma associated antigen in patients following
cyclophosphamide conditioning.

II. Evaluate the functional and numeric in vivo persistence of adoptively transferred IL-21
modulated CTL and factors contributing to immunopotentiation in patients receiving IL-21
modulated CTL following cyclophosphamide conditioning.


I. Evaluate the antitumor effect of adoptively transferred IL-21 modulated CD8+
antigen-specific CTL following cyclophosphamide conditioning and post-infusion IL-2.


Patients receive cyclophosphamide intravenously (IV) on days -3 and -2 followed by an
infusion of IL-21 modulated, melanoma antigen recognized by T cell (MART)-1 specific CD8+
cytotoxic T lymphocytes over 30-60 minutes on day 0. Beginning within 24 hours of T-cell
infusion, patients receive low-dose aldesleukin subcutaneously (SC) twice daily (BID) for 14
days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed for 8-10 weeks.

Inclusion Criteria:


- Pulse > 45 or < 120

- Weight >= 45 kg

- Temperature =< 38 Celsius (C) (=< 100.4 Fahrenheit [F])

- White blood cells (WBC) >= 3000

- Hematocrit (HCT) >= 30%

- Platelets >= 100,000


- Histopathological documentation of melanoma concurrent with the diagnosis of
metastatic disease

- Tumor expression of MART-1 (2+ staining or > 25%) by immunohistochemistry (IHC)

- Able to tolerate high-dose cyclophosphamide

- Expression of human leukocyte antigen (HLA)-A2

- Zubrod performance status of 0-1

- Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic
imaging (X-ray, computed tomography [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 or hypertension

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 (CrCl) < 75 ml/min (calculated:
Cockcroft and Gault equation: CrCl = (140 - age) x ideal body weight (IBW)/(serum
creatinine [Scr] x 72) (x 0.85 for females)

- Serum glutamic oxaloacetic transaminase (SGOT) > 150 IU or > 3 x upper limit of

- Direct bilirubin > 1.0 mg/dL

- Prothrombin time > 1.5 x control (in the absence of systemic anticoagulation)

- Clinically significant pulmonary dysfunction, as determined by medical history and
physical exam; patients so identified will undergo pulmonary functions testing at the
discretion of their primary physician

- 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 electrocardiogram (EKG) requiring drug therapy

- Symptomatic central nervous system metastases greater than 1 cm at time of therapy;
patients with 1-2 asymptomatic, less than 1cm brain/central nervous system (CNS)
metastases without significant edema may be considered for treatment; if
sub-centimeter CNS lesions are noted at study entry, then 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 immunodeficiency syndrome (AIDS) or human immunodeficiency
virus (HIV)-1 associated complex or known to HIV antibody seropositive or known to be
recently polymerase chain reaction positive (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

- Patients who, in the opinion of their physician, are not clinically suited for
high-dose cytoxan

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Safety and toxicity as assessed by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v 3.0

Outcome Time Frame:

10 weeks post infusion

Safety Issue:


Principal Investigator

Cassian Yee

Investigator Role:

Principal Investigator

Investigator Affiliation:

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium


United States: Institutional Review Board

Study ID:




Start Date:

April 2010

Completion Date:

Related Keywords:

  • Stage IV Melanoma
  • Melanoma



Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium Seattle, Washington  98109