Universal Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF)-Producing and CD40L Expressing Bystander Cell Line for Tumor Vaccine in Melanoma

Phase 2

Completed

Brief Summary: The purpose of this study is to find out what effects (good and/or bad) this new cancer vaccine has on the patient and their cancer, whether it is safe and whether it can help get rid of their cancer (malignant melanoma). We want to check how the patient's immune system reacts, both before and after the vaccine treatment.

Detailed Description: The vaccine will be made by mixing two kinds of cells: 1) some of the patient's own malignant melanoma cells which were removed by surgery and then processed in the Cell Therapy Laboratory, and 2) experimental "bystander" cells. All the cells in the vaccine will be treated with high-dose X-rays to make sure that none of them grow and cause more cancer. The bystander cells, called "GM.CD40L", are human cells that have been genetically changed. The original cells, called K562, had the genes for human GM-CSF and CD40L inserted into them. These changes are designed to help boost the patient's immune system to better fight the cancer in their body.

Recruitment & Eligibility

Inclusion Criteria

Histologically confirmed stage IIIC or stage IV melanoma
Measurable disease
Age 18 or older
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
No radiation therapy within 2 weeks prior to first vaccine administration
No chemotherapy within 4 weeks prior to first vaccine administration
No steroid therapy within 4 weeks prior to first vaccine administration
No surgery within 10 days prior to first vaccine administration
Patient's written informed consent
Patient's ability to comply with the visit schedule and assessments required by the protocol
Adequate organ function (measured within a week of beginning treatment):
- White blood count (WBC) > 3,000/mm^3 and absolute neutrophil count (ANC) >1500/mm^3
- Platelets > 100,000/mm^3
- Hematocrit > 25% and Hgb > 8 g/dL
- Bilirubin < 2.0 mg/dL
- Creatinine < 2.0 mg/dL, or creatinine clearance > 60 mL/min

Exclusion Criteria

Symptomatic or untreated brain metastasis
Any serious ongoing infection
Current corticosteroid or other immunosuppressive therapy
Any other pre-existing immunodeficiency condition (including known HIV infection)
Pregnant or lactating women -- Patients in reproductive age must agree to use contraceptive methods for the duration of the study (*A pregnancy test will be obtained before treatment)
ECOG performance status of 2, 3, or 4
Any second active primary cancer

Arm && Interventions

Group	Intervention	Description
Vaccine Therapy	Bystander-Based Autologous Tumor Cell Vaccine	Treatment consisted of intradermal vaccine injections at 28-day intervals for a total of 3 immunizations. Injections were performed on Days 1, 29, and 57.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Partial Response	Average of 14 months	Response and progression were evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Serious Adverse Events (SAEs) Related to Study Treatment	Average of 14 months	Frequency of Study Related Toxicity. To evaluate the toxicity of the autologous tumor cell / GM.CD40L bystander cell vaccine. Toxicity was scored using the NCI Common Terminology Criteria for Adverse Events Version 3.0 (CTCAE-3).
Number of Participants With Stable Disease	Average of 14 months	Patients with stable disease by RECIST criteria after 3 vaccine injections. Response and progression were evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time to Progression (TTP) in Months	Average of 14 months	Response and progression were evaluated using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Progressive disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Overall Survival (OS) in Months	Average of 14 months	Average overall survival time in months.