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

A Phase II Trial Using a Universal GM-CSF-Producing and CD40L-Expressing Bystander Cell Line (GM.CD40L) in the Formulation of Autologous Tumor Cell-Based Vaccines for Patients With Malignant Melanoma

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00101166

Enrollment

Registered

2005-01-10

Start date

2004-10-31

Completion date

2010-03-31

Last updated

2018-02-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Melanoma (Skin)

Keywords

recurrent melanoma, stage III melanoma, stage IV melanoma

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.

Interventions

BIOLOGICALBystander-Based Autologous Tumor Cell Vaccine

The vaccine, consisting of one mL of cell suspension (GM.CD40L bystander cells admixed with an equivalent number of thawed autologous tumor cells), was administered into 8 separate injection sites, as described in treatment arm.

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
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

Measure	Time frame	Description
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.

Countries

United States

Participant flow

Recruitment details

43 patients with Stage IV melanoma were enrolled between November 2004 and May 2007. Fifteen of these patients did not receive any vaccine.

Participants by arm

Arm	Count
Vaccine Therapy 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. Bystander-Based Autologous Tumor Cell Vaccine : The vaccine, consisting of one mL of cell suspension (GM.CD40L bystander cells admixed with an equivalent number of thawed autologous tumor cells), was administered into 8 separate injection sites, as described in treatment arm.	28
Total	28

Arm

Count

Vaccine Therapy

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. Bystander-Based Autologous Tumor Cell Vaccine : The vaccine, consisting of one mL of cell suspension (GM.CD40L bystander cells admixed with an equivalent number of thawed autologous tumor cells), was administered into 8 separate injection sites, as described in treatment arm.

Total

Withdrawals & dropouts

Period	Reason	FG000
Overall Study	progressive disease	10

Baseline characteristics

Characteristic	Vaccine Therapy
Age, Continuous	60 years
Region of Enrollment United States	28 participants
Sex: Female, Male Female	8 Participants
Sex: Female, Male Male	20 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	10 / 28
serious Total, serious adverse events	0 / 28

Outcome results

Primary

Number of Participants With Partial Response

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.

Time frame: Average of 14 months