Clinical trial NCT00390338: Vaccine Therapy in Treating Patients With Stage III or Stage IV Melanoma
Official title: Phase I Evaluation of Alpha-Type-1 DC-Based and cDC-Based Intralymphatic Vaccines in Patients With Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma (Skin)
Keywords: recurrent melanoma
stage IV melanoma
stage IIIA melanoma
stage IIIB melanoma
stage IIIC melanoma
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2006-10-19
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Safety of intralymphatic autologous type-1-polarized dendritic cell vaccine and autologous mature dendritic cell vaccine
timeFrame: 7 years
Secondary outcomes:
measure: Assess immune responses to each dendritic cell vaccine outcome
timeFrame: 7
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: UPMC Cancer Center at Magee-Womens Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Cancer Centers
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Ahmad A. Tarhini, MD, MS
role: PRINCIPAL_INVESTIGATOR
References: