Clinical trial NCT00045357: Biological Therapy in Treating Patients With Metastatic Melanoma
Official title: Phase I Study to Evaluate the Safety of Cellular Adoptive Immunotherapy Using Autologous CD4+ Antigen-Specific T Cell Clones for Patients With Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma (Skin)
Keywords: recurrent melanoma
stage IV melanoma
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2003-07-08
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Biological therapies use different ways to stimulate the immune system and stop tumor cells from growing. Treating a person's white blood cells in the laboratory and reinfusing them may cause a stronger immune response and kill more tumor cells.

PURPOSE: Phase I trial to study the effectiveness of biological therapy in treating patients who have metastatic melanoma.

Detailed description: OBJECTIVES:

Primary

* 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.

Secondary

* 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 weeks.

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

Eligibility criteria: DISEASE CHARACTERISTICS:

* 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

PATIENT CHARACTERISTICS:

Age

* 18 to 75

Performance status

* Karnofsky 70-100%

Life expectancy

* More than 16 weeks

Hematopoietic

* 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%

Hepatic

* 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

Renal

* Creatinine no greater than 2.0 mg/dL OR
* Creatinine clearance at least 60 mL/min
* Calcium no greater than 12 mg/dL

Cardiovascular

* 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

Pulmonary

* No clinically significant pulmonary dysfunction
* FEV1 at least 1.0 L OR
* FEV1 at least 60%
* DLCO at least 55% (corrected for hemoglobin)

Immunologic

* 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

Other

* 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

PRIOR CONCURRENT THERAPY:

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)

Chemotherapy

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

Endocrine therapy

* No concurrent systemic steroids except for toxicity management

Radiotherapy

* At least 4 weeks since prior radiotherapy

Surgery

* Not specified

Other

* 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
Study officials:
affiliation: Fred Hutchinson Cancer Center
name: Cassian Yee, MD
role: STUDY_CHAIR
References: