Clinical trial NCT00085488: Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma
Official title: En Vivo Matured Dendritic Cell Therapy in Patients With Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma (Skin)
Keywords: recurrent melanoma
stage III melanoma
stage IV melanoma
Lead sponsor: Dartmouth-Hitchcock Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-06-11
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Vaccines made from a patient's dendritic cells and tumor cells may make the body build an immune response to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vaccine therapy in treating patients with stage III or stage IV melanoma.

Detailed description: OBJECTIVES:

Primary

* Determine the dose-limiting toxicity and the maximum tolerated dose of autologous dendritic cells pulsed with autologous tumor cell lysate in patients with stage III or IV melanoma.
* Determine the safety and tolerability of this therapy in these patients.

Secondary

* Determine the immune response, in terms of the type and degree of T-cell proliferation and delayed-type hypersensitivity responses, in patients treated with this therapy.

OUTLINE: This is a dose-escalation, pilot study.

Patients undergo leukapheresis for the collection of peripheral blood mononuclear cells (PBMC) on days -9, 19, and 47. Autologous dendritic cells (DC) are prepared from autologous PBMC exposed to sargramostim (GM-CSF), interleukin-4, and tumor necrosis factor alpha and pulsed with autologous tumor cell lysate. Patients receive autologous tumor cell lysate-pulsed DC IV over 5-10 minutes on days 0, 28, and 56.

Cohorts of 3-6 patients receive escalating doses of autologous tumor cell lysate-pulsed DC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which 33% of all patients experience dose-limiting toxicity.

Patients are followed at day 84 and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 3-20 patients will be accrued for this study within 3-20 months.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed melanoma

  * Stage III (lymph node or in-transit metastases) or IV (systemic metastases) disease
* Patients with relapsed disease OR who failed prior immunotherapy or chemotherapy are eligible (but trial not restricted to relapsed or refractory disease)
* Tumor tissue available and properly stored for lysate preparation

PATIENT CHARACTERISTICS:

Age

* 18 and over

Performance status

* Karnofsky 60-100%

Life expectancy

* At least 12 weeks

Hematopoietic

* Absolute neutrophil count ≥ 1,000/mm\^3
* Platelet count ≥ 75,000/mm\^3

Hepatic

* AST ≤ 2 times upper limit of normal (ULN) (3 times ULN for liver metastases)
* Bilirubin ≤ 2 times ULN
* Hepatitis B surface antigen negative
* Hepatitis C negative

Renal

* Creatinine ≤ 2.0 times ULN

Immunologic

* No active infection
* No history of autoimmune disease, including any of the following:

  * Inflammatory bowel disease
  * Systemic lupus erythematosus
  * Scleroderma
  * Rheumatoid arthritis
  * Multiple sclerosis
* No allergy to aminoglycosides or streptomycin
* HIV negative

Other

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No significant comorbid illness
* No other malignancy within the past 5 years except nonmelanoma skin cancer or carcinoma in situ of the cervix

PRIOR CONCURRENT THERAPY:

Biologic therapy

* See Disease Characteristics
* At least 10 days since prior immunotherapy

Chemotherapy

* See Disease Characteristics

Endocrine therapy

* At least 6 weeks since prior steroid therapy
* No concurrent corticosteroids

Radiotherapy

* At least 10 days since prior radiotherapy
* No concurrent radiotherapy

Surgery

* At least 10 days since prior surgery
* Prior diagnostic or palliative surgery allowed provided the patient has fully recovered

Other

* No concurrent immunosuppressive or potentially immunosuppressive therapy

Primary outcomes:
measure: Ex Vivo Matured Dendritic Cell Therapy in Patients with Melanoma
timeFrame: 2005-2006
Secondary outcomes:
Other outcomes:
Locations:
city: Lebanon
country: United States
facility: Norris Cotton Cancer Center at Dartmouth-Hitchcock Medical Center
state: New Hampshire
Study officials:
affiliation: Norris Cotton Cancer Center
name: Christopher P. Tretter, MD
role: STUDY_CHAIR
References: