Clinical trial NCT00005617: Vaccine Therapy in Treating Patients With Stage IV or Relapsed Malignant Melanoma
Official title: A Phase I Trial Testing Mart-1 Peptide Immunization in Malignant Melanoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Melanoma
Keywords: stage IV melanoma
recurrent melanoma
Lead sponsor: Jonsson Comprehensive Cancer Center
Sponsor class: OTHER
First posted: 2003-01-27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: Vaccines made from peptides may make the body build an immune response to kill tumor cells.

PURPOSE: Phase I/II trial to study the effectiveness of vaccine therapy in treating patients who have stage IV, or relapsed malignant melanoma.

Detailed description: OBJECTIVES:

* Determine the safety of administering MART-1 peptide-pulsed dendritic cells to patients with stage IV or relapsed malignant melanoma.
* Determine the immunological and clinical responses in this patient population after this therapy.

OUTLINE: This is a dose-escalation study.

Patients undergo leukapheresis between days -14 to -8. Mononuclear cells are isolated, used to generate dendritic cells (DC), and then pulsed with MART-1 peptide. Patients are vaccinated with MART-1 peptide-pulsed DC either IV or intradermally on days 0, 14, and 28.

Cohorts of 3-6 patients receive escalating doses of MART-1 peptide-pulsed DC until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

Patients are followed until death.

PROJECTED ACCRUAL: A total of 18-24 patients will be accrued for this study.

Eligibility criteria: Inclusion Criteria:

* Adults over the age of 18 with malignant melanoma.
* HLA-A2.1 positive and express MART-1, as assessed by either RT-PCR or by immunohistochemistry
* Tumor stages T3N0M0 or greater are eligible for this trial according to the following:

  1. I (\<.75 to 1.5 mm or Clark level III-T1-2N0M0-)-not eligible
  2. II (1.5 to 4 mm or level IV-T3N0M0-)-eligible
  3. III (limited nodal metastasis involving one regional lymph node basin, or fewer than 5 in-transit metastasis -TxN1M0-)-eligible
  4. IV (advanced regional metastasis -TxN2M0- or any distant metastasis -TxNxM1-)-eligible
  5. Relapsed melanoma-eligible
* Patients previously treated with any form of therapy for either metastatic, relapsed or primary melanoma are eligible for this trial, provided that previous treatment was completed \>30 days prior to enrollment
* Both male and females may be enrolled. Premenopausal females must have a negative pregnancy test prior to treatment
* Karnofsky Performance Status greater than or equal to 70 percent
* No previous evidence of class 3 or greater New York Heart Association cardiac insufficiency or coronary artery disease
* No previous evidence of opportunistic infection
* A minimum of 30 days must have elapsed since the completion of prior chemotherapy, immunotherapy or radiation therapy
* Adequate baseline hematological function as assessed by the following laboratory values within 30 days prior to study entry (day -30 to 0):

  1. Hemoglobin \>9.0 g/dl
  2. Platelets \> 100000/mm3
  3. WBC \> 3000/mm3
  4. Absolute Neutrophil Count \> 1000/mm3
* Positive skin test to common antigens (tetanus and candida)
* Ability to give informed consent

Exclusion Criteria:

* Lactating females and females of child-bearing potential must have negative serum beta-HCG pregnancy test
* Acute infection: any acute viral, bacterial, or fungal infection which requires specific therapy. Acute therapy must have been completed within 14 days of prior to study treatment
* HIV-infected patients
* Acute medical problems such as ischemic heart or lung disease that may be considered an unacceptable anesthetic or operative risk
* Patients with any underlying conditions which would contraindicate therapy with study treatment (or allergies to reagents used in this study)
* Patients with organ allografts
* Uncontrolled CNS metastasis. Patients with CNS metastasis will be eligible if they have received CNS irradiation to control local tumor growth

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center, UCLA
state: California
Study officials:
affiliation: Jonsson Comprehensive Cancer Center
name: John A Glaspy, MD
role: PRINCIPAL_INVESTIGATOR
References: