Melanoma
Conditions
Brief summary
Randomized trial to determine if neo-adjuvant subcutaneous GM-CSF restores the host regional lymph node immunity
Detailed description
The sentinel lymph nodes in patients with melanoma are immunosuppressed and the investigators have shown this occurs early in the disease process. This regional nodal immunosuppression precedes nodal metastasis and may be required for nodal spread. Administration of GM-CSF has been used to alter the immune response to metastatic melanoma. The investigators propose to assess whether administration of a short course of GM-CSF preoperatively to patients about to undergo wide local excisions and sentinel lymph node dissection can alter the immune environment of the sentinel lymph node and restore an immune surveillance profile in the sentinel lymph node.
Interventions
DRUGGM-CSF
14 days in a dose of 125 µg/m\^2
OTHERStandard of Care
No neo-adjuvant therapy prior to surgical intervention
Sponsors
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
To be eligible for the study, patients must satisfy the following criteria: * Histologically confirmed primary cutaneous malignant melanoma * 1-4mm Breslow depth * Scheduled for sentinel lymph node biopsy as part of their standard surgical management * Man or woman, age \>/= 18 years * Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 2 weeks after the study in such a manner that the risk of pregnancy is minimized. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal. Sexually active WOCBP must use an effective method of birth control during the course of the study, in a manner such that risk of failure is minimized. All WOCBP must have a negative pregnancy test prior to first receiving GM-CSF. * Men must agree to use and utilize an adequate method of contraception throughout treatment and for at least 2 weeks after study drug is stopped * All patients must be willing and able to give written informed consent.
Exclusion criteria
Subjects meeting any of the following criteria are ineligible for study entry * Clinical stage III or IV disease * Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of immunologic disease (e.g. rheumatoid arthritis, scleroderma, systemic lupus erythematosus, autoimmune vasculitis, motor neuropathy considered of autoimmune origin) * Any underlying medical conditions which, in the opinion of the investigator, will make the administration of GM-CSF hazardous or obscure the interpretation of adverse events; such as, psychological, familial, sociological or geographical conditions potentially hampering compliance with the study protocol and followup schedule * Any vaccination therapy within 4 weeks prior to GM-CSF administration * Concomitant therapy with any of the following within the past 3 months: GM-CSF, interferon, other non-study immunotherapy regimes; cytotoxic chemotherapy * Immunosuppressive mediations (steroids, tumor necrosis factor (TNF)-inhibitors, azathioprine, etc.) within the past 6 weeks * Active or chronic infection with HIV, hepatitis B or hepatitis C * WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and 2 weeks after cessation of the study drug. * Prisoners or subjects who are compulsorily detained
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Th1/Th2 Normalized Gene Expression | 14 days post treatment | The Th1/Th2/Th3 Reverse transcription polymerase chain reaction (RT-qPCR) arrays will be used to quantify RNA expression of Th1 and Th2 messenger ribonucleic acids (mRNAs). Normalized gene expression was calculated from qRT-PCR results comparing GM-CSF and control subjects for both Th1-associated gene T-bet and Th2-associated gene GATA3 respectively. Fold change values are calculated by taking the normalized gene expression in GM-CSF treated group samples divided by the normalized gene expression in the control group samples. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| GM-CSF Patients will be treated with 14 days of GM-CSF self-administered subcutaneously daily for 14 days in a dose of 125 µg/m2 beginning on the day of enrollment. Patients will be instructed in the self-administration of GM-CSF and after they have demonstrated competency with the procedure, they will self-administer the treatment at home. Patients will undergo surgery within 1 day to 5 days after cessation of the GM-CSF therapy.
GM-CSF: 14 days in a dose of 125 µg/m\^2 | 4 |
| Standard of Care no neo-adjuvant therapy prior to surgical intervention
Standard of Care: No neo-adjuvant therapy prior to surgical intervention | 4 |
| Total | 8 |
Baseline characteristics
| Characteristic | Standard of Care | Total | GM-CSF |
|---|---|---|---|
| Age, Continuous | 62.7 years STANDARD_DEVIATION 18.8 | 58.6 years STANDARD_DEVIATION 16.1 | 54.5 years STANDARD_DEVIATION 14.3 |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 4 participants | 8 participants | 4 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 0 |
| other Total, other adverse events | 0 / 4 | 0 / 0 |
| serious Total, serious adverse events | 0 / 4 | 0 / 0 |
Outcome results
Primary
Th1/Th2 Normalized Gene Expression
The Th1/Th2/Th3 Reverse transcription polymerase chain reaction (RT-qPCR) arrays will be used to quantify RNA expression of Th1 and Th2 messenger ribonucleic acids (mRNAs). Normalized gene expression was calculated from qRT-PCR results comparing GM-CSF and control subjects for both Th1-associated gene T-bet and Th2-associated gene GATA3 respectively. Fold change values are calculated by taking the normalized gene expression in GM-CSF treated group samples divided by the normalized gene expression in the control group samples.
Time frame: 14 days post treatment
Population: Three subjects were in in the GM-CSF group and three subjects were in the Standard of Care group. One subject in the GM-CSF group received GM-CSF but did not have tissue sample collected for research analysis. One subject in the Standard of Care group did not have a large enough tissue sample collected to be analyzed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| GM-CSF | Th1/Th2 Normalized Gene Expression | T-bet (Th1) | 1.029 fold change |
| GM-CSF | Th1/Th2 Normalized Gene Expression | GATA3 (Th2) | 0.074 fold change |
| Standard of Care | Th1/Th2 Normalized Gene Expression | T-bet (Th1) | 0.119 fold change |
| Standard of Care | Th1/Th2 Normalized Gene Expression | GATA3 (Th2) | 0.192 fold change |