Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma

University Hospital Erlangen

Status and phase

Completed

Phase 2

Phase 1

Conditions

Melanoma (Skin)

Treatments

Biological: Dendritic cell vaccine plus denileukin difitox

Study type

Interventional

Funder types

Other

Identifiers

NCT00056134

EU-20246

CDR0000270762

ERLANGEN-ONTAK

Details and patient eligibility

About

RATIONALE: Vaccines made from a person's white blood cells mixed with tumor proteins may make the body build an immune response to kill tumor cells. Biological therapies such as denileukin diftitox may be able to deliver cancer-killing substances directly to melanoma cells. Combining vaccine therapy with biological therapy may kill more tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of combining vaccine therapy with denileukin diftitox in treating patients who have stage III or stage IV melanoma.

Full description

OBJECTIVES:

Compare the efficacy of vaccination with autologous dendritic cells pulsed with tumor and influenza antigen peptides with or without ex vivo CD40-ligand and denileukin diftitox, in terms of tumor-specific T-cell response, in patients with HLA-A1- and/or HLA-A2.1-positive stage III or IV melanoma.
Determine the safety and tolerability of these vaccinations in these patients.
Determine tumor response in patients treated with these vaccinations.

OUTLINE:

Phase I (Administration of denileukin diftitox and vaccinations #1 to #4): Patients undergo leukapheresis for collection of peripheral blood mononuclear cells (PMBC). PBMC are processed for the generation of dendritic cells (DC) to be used for vaccinations. DC are pulsed with HLA-A1- and HLA-A2.1-restricted peptides derived from melanoma-associated tumor antigens. DC are pulsed with or without ex vivo treatment with CD40-ligand. Patients receive denileukin diftitox IV for 3 consecutive days before the first vaccination. Patients receive 4 pulsed DC vaccinations subcutaneously (SC) on days 1, 14, 42, and 70 in the absence of disease progression or unacceptable toxicity.

Patients who show a tumor response (at least stable disease) may receive vaccination #5 and further booster vaccinations.

Phase II: DC are generated and pulsed as in phase I. Patients receive up to 6 additional booster pulsed DC vaccinations SC on days 126, 184, 268, 356, 520, and 692 in the absence of disease progession or unacceptable toxicity.

Patients are followed for 10 years.

PROJECTED ACCRUAL: A total of 8-30 patients will be accrued for this study within 6-12 months.

Enrollment

23 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Histologically confirmed locoregional or metastatic cutaneous malignant melanoma
- Stage III or IV disease
  - Stage III: pT4b, N0, M0 (satellite metastases) or any pT, N1 or pT, N1 or N2a-c, M0 (lymph node metastases or in transit intralymphatic metastases)
  - Stage IV: any pT, N1-2, M1a-b
  - Surgically incurable
  - Incurable with standard treatment (i.e., localized chemotherapy/limb perfusion for stage III, systemic chemotherapy for stage IV)
Unidimensionally or bidimensionally measurable disease by physical examination (e.g., cutaneous metastases) and/or non-invasive radiologic procedures NOTE: Stage III lesions may be measurable lymph nodes after incomplete resection and/or inoperable in transit metastases
HLA-A1 and/or HLA-A2 expression by serologic HLA typing
- HLA-A2.01 subtype must be confirmed by polymerase chain reaction on genomic DNA obtained from peripheral blood mononuclear cells
No active CNS metastases
- Previously treated CNS metastases (e.g., excision of a single metastasis) allowed if no active disease present by CT scan or MRI

PATIENT CHARACTERISTICS:

Age

Over 18

Performance status

Karnofsky 60-100%

Life expectancy

At least 6 months

Hematopoietic

WBC greater than 2,500/mm^3
Neutrophil count greater than 1,000/mm^3
Lymphocyte count greater than 700/mm^3
Platelet count greater than 75,000/mm^3
Hemoglobin greater than 9 g/dL
No bleeding disorders

Hepatic

Bilirubin less than 2.0 mg/dL
No hepatitis B or C

Renal

Creatinine less than 2.5 mg/dL

Cardiovascular

No clinically significant heart disease

Pulmonary

No clinically significant respiratory disease

Immunologic

No active systemic infection
No immunodeficiency disease
- No evidence of HIV-1, HIV-2, or human T-cell lymphocytic virus-1
No active autoimmune disease including, but not limited to:
- Lupus erythematosus
- Autoimmune thyroiditis or uveitis
- Multiple sclerosis
- Inflammatory bowel disease NOTE: Vitiligo allowed

Other

Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for 4 weeks after study participation
No organic brain syndrome or significant psychiatric abnormality that would preclude study participation and follow-up
No contraindication to leukapheresis
No other active malignant neoplasms

PRIOR CONCURRENT THERAPY:

Biologic therapy

More than 4 weeks since prior systemic immunotherapy
No concurrent immunotherapy during and for 2 weeks after last vaccination

Chemotherapy

See Disease Characteristics
More than 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas [e.g., fotemustine])
No concurrent chemotherapy during and for 2 weeks after last vaccination

Endocrine therapy

No concurrent corticosteroids during and for 2 weeks after last vaccination

Radiotherapy

No prior radiotherapy to the spleen
Concurrent palliative radiotherapy allowed for selected metastases (e.g., pain or local complications such as compression)

Surgery

See Disease Characteristics
Recovered from prior surgery
No prior splenectomy
No prior organ allografts
Concurrent surgery of selected metastases (e.g., pain or local complications such as compression) allowed

Other

No other concurrent investigational drugs during and for 2 weeks after last vaccination
No concurrent paramedical substance during and for 2 weeks after last vaccination
No concurrent participation or intent to participate in another clinical trial