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

Pawel Kalinski

Status and phase

Completed

Phase 1

Conditions

Melanoma (Skin)

Treatments

Biological: non-polarized dendritic cells

Biological: polarized dendritic cells

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00390338

03-118

CDR0000504518 (Registry Identifier)

NCI-7089

PCI-IRB-0409071

NCI-2009-00125 (Registry Identifier)

PCI-UPCI-03-118

Details and patient eligibility

About

RATIONALE: Vaccines made from a person's dendritic cells mixed with tumor peptides and proteins may help the body build an effective immune response to kill tumor cells. Infusing the vaccine directly into the lymphatic system may cause a stronger immune response and kill more tumor cells.

PURPOSE: This randomized phase I trial is studying the side effects and best dose of two dendritic cell vaccines in treating patients with stage III or stage IV melanoma.

Full description

OBJECTIVES:

Primary

Compare the safety of intralymphatic autologous type-1-polarized dendritic cell vaccine vs autologous mature dendritic cell vaccine loaded with antigenic peptides and proteins in patients with stage III or IV melanoma.

Secondary

Determine peripheral blood CD8+ and CD4+ T-cell responses to HLA-presented melanoma epitopes and autologous tumor cells using interferon gamma and interleukin-5 ELISPOT assay.
Compare the delayed-type hypersensitivity (DTH) responses to these regimens and DTH to autologous tumor lysates in these patients.
Compare the DTH response to keyhole limpet hemocyanin and pan-DR epitope (PADRE) in these patients.
Correlate treatment-associated changes in immune response with clinical outcome.

OUTLINE: This is a randomized, open-label, dose-escalation study. Patients are randomized to 1 of 2 formulations of dendritic cell (DC) vaccines.

Arm I: Patients receive intralymphatic autologous type-1-polarized (by interleukin-1-beta, tumor necrosis factor [TNF] alfa, interferon alfa, poly-I:C, and interferon gamma) DC vaccine that has been loaded with tumor-related peptide antigens (gp100:209-217[210M] peptide, tyrosinase peptide, MART-1:27-35 peptide, MAGE-3/6, and EphA2) and proteins (keyhole limpet hemocyanin [KLH; first course] or pan-DR epitope [PADRE] [second course]) every 6 hours on days 1-4 of weeks 1 and 6.
Arm II: Patients receive intralymphatic autologous mature (by interleukin-1-beta, TNF alfa, interleukin-6, and prostaglandin E_2) DC vaccine that has been loaded with tumor-related peptide antigens and proteins as in arm I every 6 hours on days 1-4 of weeks 1 and 6.

Patients achieving complete response receive 2 more courses of treatment (3 months apart). Patients achieving partial response receive up to 10 more courses of treatment (1 month apart) in the absence of disease progression or unacceptable toxicity.

In each arm, cohorts of 4-7 patients receive escalating doses of DC vaccine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 7 patients experience dose-limiting toxicity.

Blood samples are obtained at baseline and periodically during and after treatment. Samples are examined by immunoenzyme techniques for immunologic measurements.

After completion of study therapy, patients are followed periodically for 10½ years and then annually thereafter.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study.

Enrollment

22 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Pathologically confirmed stage III or IVA (M1a) melanoma
- Recurrent and inoperable disease
- Any tumor thickness and any number of lymph nodes involved
- Asymptomatic cutaneous and nodal disease allowed
- Asymptomatic pulmonary metastatic disease (stage IVB, M1b) allowed
No advanced symptomatic visceral disease, including any symptomatic visceral organ involvement, or disease associated with increased serum lactic dehydrogenase > 2.5 times upper limit of normal (stage IVC, M1c)
Standard curative or palliative measures do not exist or are no longer effective
Sufficient numbers of monocytes (≥ 20 x 10^6) must be obtained for the preparation of the vaccine
- If an insufficient number of cells is obtained on first venipuncture, a second venipuncture may be performed (not exceeding 550 mL of blood within 8 weeks)
No brain metastases by contrast-enhanced CT scan or MRI
- Prior brain metastases allowed provided they were successfully treated and patient has been asymptomatic for ≥ 3 months
HLA-A2 positive

PATIENT CHARACTERISTICS:

ECOG performance status 0-1
Life expectancy ≥ 6 months
Granulocyte count ≥ 1,500/mm³
Lymphocyte count ≥ 500/mm³
Platelet count > 70,000/mm³ (for venipuncture/pheresis procedure)
Creatinine ≤ 1.5 times upper limit of normal (ULN)
AST and ALT ≤ 2.5 times ULN
Gamma-glutamyl transferase ≤ 2.5 times ULN
Lactic dehydrogenase ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN
Bilirubin ≤ 1.5 times ULN
No active infection
No sensitivity to drugs that provide local anesthesia
No pain uncontrolled by oral analgesics, including opiates and opiate analogs
No active autoimmune disease
No HIV, hepatitis B, or hepatitis C positivity
Not pregnant or nursing
Fertile patients must use effective contraception
Negative pregnancy test
No other malignancy except for nonmelanoma skin cancers or carcinoma in situ of the cervix, or other malignancy for which the patient has been continuously disease-free for ≥ 2 years

PRIOR CONCURRENT THERAPY:

Recovered from prior surgery
No radiotherapy, chemotherapy, or immunotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin C)
No antibiotics within the past 7 days
No systemic immunosuppressive agents, including steroids, within the past 4 weeks
- Concurrent maintenance steroids for adrenal insufficiency allowed
No other concurrent anticancer investigational or commercial agents or therapies