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Vaccination Of HLA-A1 And/Or -A2+ Stage III or IV Melanoma Patients With Tumor Peptide - Loaded Autologous Dendritic Cells That Are Generated In The Absence Or Presence Of CD40 Ligand


Phase 1/Phase 2
18 Years
N/A
Open (Enrolling)
Both
Melanoma (Skin)

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Trial Information

Vaccination Of HLA-A1 And/Or -A2+ Stage III or IV Melanoma Patients With Tumor Peptide - Loaded Autologous Dendritic Cells That Are Generated In The Absence Or Presence Of CD40 Ligand


OBJECTIVES:

- Compare the efficacy of vaccination with autologous dendritic cells pulsed with tumor
and influenza antigen peptides treated with vs without ex vivo CD40-ligand, 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 and recurrence rates in patients treated with these
vaccinations.

OUTLINE: This is an open-label non-randomized study.

- Phase I: Patients undergo leukapheresis for collection of peripheral blood mononuclear
cells (PBMC). PBMC are cultured with sargramostim (GM-CSF) and interleukin-4 to
generate dendritic cells (DCs) on day -9. DCs are pulsed separately with HLA-A1 and
HLA-A2.1-restricted flu matrix peptides derived from melanoma-associated tumor antigens
(MAGE-10.A2, Melan-A, MAGE-3, NY-ESO-1, gp100 antigen, and tyrosinase peptide). Half of
the DCs are treated ex vivo with CD40-ligand. Patients receive the peptide-pulsed DC
vaccinations subcutaneously (SC) on days 1, 14, 42, and 70 in the absence of disease
progression.

Patients who show tumor response (at least stable disease) at day 98 progress to phase II of
the study.

- Phase II: Patients undergo leukapheresis as in phase I on days 102, 352, and 688.
Patients receive up to 6 additional booster vaccinations SC as in phase I on days 126,
184, 268, 356, 520, and 692.

Patients are followed for 10 years.

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

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed stage III or IV cutaneous malignant melanoma

- HLA-A1 and/or HLA-A2 expression by serologic HLA typing

- HLA-A2.1 subtype must be confirmed by polymerase chain reaction on genomic DNA
obtained from peripheral blood mononuclear cells

- No active CNS metastases by CT scan or MRI

PATIENT CHARACTERISTICS:

Age

- Over 18

Performance status

- Karnofsky 60-100%

Life expectancy

- At least 4 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

- Hepatitis B surface antigen negative

- Hepatitis C antibody negative

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 lymphotropic virus-1

- No active autoimmune disease including (but not limited to):

- Lupus erythematosus

- Autoimmune thyroiditis or uveitis

- Multiple sclerosis

- Inflammatory bowel disease

Other

- Stable medical condition

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception during and for at least 1 month
after study participation

- No organic brain syndrome or psychiatric illness that would preclude study compliance

- No other concurrent active malignancy

- No other concurrent serious illness that would preclude study treatment

- No contraindication to leukapheresis

PRIOR CONCURRENT THERAPY:

Biologic therapy

- More than 4 weeks since prior immunotherapy

- No other concurrent immunotherapy

Chemotherapy

- More than 4 weeks since prior systemic chemotherapy (6 weeks for nitrosoureas)

- No concurrent chemotherapy

Endocrine therapy

- No concurrent corticosteroids

Radiotherapy

- More than 4 weeks since prior radiotherapy

- No prior radiotherapy to the spleen

- Concurrent palliative radiotherapy allowed

Surgery

- Recovered from prior surgery

- No prior splenectomy

- No prior organ allograft

- Concurrent surgery on selected metastases (e.g., because of pain or local
complications such as compression) allowed

Other

- No other concurrent investigational drugs

- No concurrent participation in another clinical trial

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Comparison of the efficacy of vaccination with vs without ex vivo CD40-ligand in terms of tumor-specific T-cell response

Safety Issue:

No

Principal Investigator

Gerold Schuler

Investigator Role:

Study Chair

Investigator Affiliation:

Dermatologische Klinik MIT Poliklinik-Universitaetsklinikum Erlangen

Authority:

United States: Federal Government

Study ID:

CDR0000258491

NCT ID:

NCT00053391

Start Date:

October 2002

Completion Date:

Related Keywords:

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

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