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Phase I Study to Evaluate the Safety of Cellular Adoptive Immunotherapy Using Autologous CD4+ Antigen-Specific T Cell Clones for Patients With Metastatic Melanoma

Phase 1
18 Years
75 Years
Not Enrolling
Melanoma (Skin)

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Trial Information

Phase I Study to Evaluate the Safety of Cellular Adoptive Immunotherapy Using Autologous CD4+ Antigen-Specific T Cell Clones for Patients With Metastatic Melanoma



- Determine the maximum tolerated dose of autologous CD4+ antigen-specific T-cells for
cellular adoptive immunotherapy in patients with metastatic melanoma.

- Determine the safety and toxicity of this regimen in these patients.

- Determine the duration of in vivo persistence of adoptively transferred CD4+
antigen-specific T-cell clones in these patients.


- Determine the antitumor effects of this regimen in these patients.

OUTLINE: This is a dose-escalation study.

Patients undergo leukapheresis to collect peripheral blood mononuclear cells. CD4+
antigen-specific T-cell clones are generated over the next 2-3 months using immunogenic
peptides MART1, tyrosinase, or gp100.

Patients receive autologous CD4+ antigen-specific T-cells IV over 30 minutes.

Cohorts of 3-6 patients receive escalating doses of autologous CD4+ antigen-specific T-cells
until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose
preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed on days 1 and 3 post T-cell infusion, and then once weekly for 12

PROJECTED ACCRUAL: A total of 3-18 patients will be accrued for this study.

Inclusion Criteria


- Histologically confirmed metastatic melanoma

- HLA type expressing one of the following class II alleles:

- DRB1*0401

- DRB1*0404

- DRB1*1501

- DPB1*0401

- DPB1*0402

- Tumor expresses tyrosinase

- Tumor expressing NY-ESO-1 and are HLA type DP4, DP2, or DR7 allowed

- No CNS metastases

- Prior CNS involvement allowed provided there is no evidence of CNS disease at
least 2 months after treatment



- 18 to 75

Performance status

- Karnofsky 70-100%

Life expectancy

- More than 16 weeks


- WBC greater than 4,000/mm^3

- Absolute neutrophil count greater than 2,000/mm^3

- Platelet count greater than 100,000/mm^3

- Hematocrit greater than 30%


- SGOT no greater than 3 times upper limit of normal

- INR no greater than 1.5 due to hepatic dysfunction

- No significant hepatic dysfunction, defined as hepatic toxicity grade 2 or greater


- Creatinine no greater than 2.0 mg/dL OR

- Creatinine clearance at least 60 mL/min

- Calcium no greater than 12 mg/dL


- No significant cardiac abnormalities*, defined by any 1 of the following:

- Congestive heart failure

- Clinically significant hypotension

- Symptoms of coronary artery disease

- Cardiac arrhythmias present on EKG requiring drug therapy NOTE: *Patients with a
history of cardiovascular disease or any of the above abnormalities undergo a
cardiac evaluation, including a cardiac stress test and/or echocardiogram


- No clinically significant pulmonary dysfunction

- FEV1 at least 1.0 L OR

- FEV1 at least 60%

- DLCO at least 55% (corrected for hemoglobin)


- No acquired or hereditary immunodeficiency

- No autoimmune disease

- No active infection

- No oral temperature greater than 38.2 degrees C within the past 72 hours

- No systemic infection requiring chronic maintenance or suppressive therapy

- HIV negative


- No retinitis or choroiditis

- No history of seizures

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for 3 months after study


Biologic therapy

- No other concurrent immunotherapy (e.g., interleukins, interferons, melanoma
vaccines, IV immunoglobulin, or expanded polyclonal tumor-infiltrating lymphocytes or
lymphokine-activated killer therapy)


- At least 4 weeks since prior chemotherapy (standard or experimental) and recovered

Endocrine therapy

- No concurrent systemic steroids except for toxicity management


- At least 4 weeks since prior radiotherapy


- Not specified


- At least 4 weeks since prior immunosuppressive therapy

- More than 4 weeks since prior experimental drugs and recovered

- No concurrent pentoxifylline

- No other concurrent investigational agents

Type of Study:


Study Design:

Primary Purpose: Treatment

Principal Investigator

Cassian Yee, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Fred Hutchinson Cancer Research Center


United States: Federal Government

Study ID:




Start Date:

November 2001

Completion Date:

August 2008

Related Keywords:

  • Melanoma (Skin)
  • recurrent melanoma
  • stage IV melanoma
  • Melanoma



Fred Hutchinson Cancer Research Center Seattle, Washington  98109