Vaccine Therapy in Treating Patients With Stage IV Melanoma

National Cancer Institute (NCI)

Status and phase: Completed; Phase 1

Conditions: Melanoma (Skin)

Treatments: Biological: gp100 antigen; Biological: dendritic cell-MART-1 peptide vaccine; Biological: tyrosinase peptide; Biological: therapeutic tumor infiltrating lymphocytes

Study type: Interventional

Funder types: NIH

Identifiers

NCT00003665

UPCC-4697

CDR0000066759 (Registry Identifier)

NCI-2012-02292

NCI-T98-0033

Details and patient eligibility

About

Randomized phase I trial to study the effectiveness of vaccine therapy in treating patients who have stage IV melanoma. Vaccines may make the body build an immune response to kill tumor cells.

Full description

OBJECTIVES:

I. Determine the dose-limiting toxicities, maximum tolerated dose, recommended phase II dose, and rate of sensitization of T cells at each dose level in patients with melanoma receiving dendritic cell vaccine.

II. Determine the overall (complete and partial) response rate, duration of response, and optimal route of administration in this patient population.

OUTLINE: This is a dose escalation study. Patients are randomized to one of three treatment arms.

All patients undergo leukopheresis to obtain lymphocyte and myeloid origin mononuclear cell fractions for preparation of dendritic cell (DC) vaccine. In each arm, cohorts of up to 5 patients receive escalating doses of vaccine. The maximum tolerated dose (MTD) is defined as the dose preceding that at which 2 or more of 5 patients experience dose-limiting toxicity. Randomization ceases if the MTD has been reached in 2 arms, although accrual may continue. Treatment repeats every 2 weeks for a total of 4 doses.

Arm I: Patients receive 3 different doses of peptide pulsed DC vaccine IV, each divided into 3 different peptide pulsed pools administered over 30 minutes.

Arm II: Patients receive 3 different doses of peptide pulsed DC vaccine subcutaneously/intradermally to sites with no evidence of disease. At the lowest dose, patients receive 3 different peptide pulsed pools, each administered at a separate site. At the higher doses, patients receive 3 injections further subdivided into 6 and administered at 6 distinct sites.

Arm III: Patients receive peptide pulsed DC vaccine intranodally in groin or ancillary lymph nodes at the lower 2 doses of the 3 administered to arms I and II. At the lower dose, patients receive 3 different peptide pulsed pools, each administered into a different node. At the higher dose, patients receive 3 injections further subdivided into 6 and administered at 6 distinct sites.

Patients are followed at 2 weeks and then monthly for 3 months.

Enrollment: 40 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

-Histologically confirmed stage IV melanoma Must be MHC Class I HLA-A2.1

PATIENT CHARACTERISTICS:

• Age: Over 18
• Performance status: ECOG 0-1
• Life expectancy: At least 2 months
• Platelet count at least 100,000/mm3
• INR no greater than 1.5 mg/dL
• No coagulopathies including thrombocytopenia
• Partial thromboplastin time no greater than 50 seconds
• No major cardiac illness
• No major respiratory illness
• No active systemic infection or other illness
• No peripheral vascular disease
• Not pregnant or nursing
• Effective contraception required of all fertile patients during and for one month after completion of treatment

PRIOR CONCURRENT THERAPY:

• At least 30 days since prior immunotherapy
• No concurrent immunotherapy
• At least 30 days since prior chemotherapy
• No concurrent chemotherapy
• At least 30 days since prior radiotherapy
• No concurrent radiotherapy

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

40 participants in 3 patient groups

Arm I

Experimental group

Description:

Patients receive 3 different doses of peptide pulsed DC vaccine IV, each divided into 3 different peptide pulsed pools administered over 30 minutes.

Treatment:

Biological: tyrosinase peptide

Biological: dendritic cell-MART-1 peptide vaccine

Biological: gp100 antigen

Biological: therapeutic tumor infiltrating lymphocytes

Arm II

Experimental group

Description:

Patients receive 3 different doses of peptide pulsed DC vaccine subcutaneously/intradermally to sites with no evidence of disease. At the lowest dose, patients receive 3 different peptide pulsed pools, each administered at a separate site. At the higher doses, patients receive 3 injections further subdivided into 6 and administered at 6 distinct sites.

Treatment:

Biological: tyrosinase peptide

Biological: dendritic cell-MART-1 peptide vaccine

Biological: gp100 antigen

Biological: therapeutic tumor infiltrating lymphocytes

Arm III

Experimental group

Description:

Patients receive peptide pulsed DC vaccine intranodally in groin or ancillary lymph nodes at the lower 2 doses of the 3 administered to arms I and II. At the lower dose, patients receive 3 different peptide pulsed pools, each administered into a different node. At the higher dose, patients receive 3 injections further subdivided into 6 and administered at 6 distinct sites.

Treatment:

Biological: tyrosinase peptide

Biological: dendritic cell-MART-1 peptide vaccine

Biological: gp100 antigen

Biological: therapeutic tumor infiltrating lymphocytes