Neoadjuvant Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Cutaneous Stage L-lll Melanoma

Sponsor
Mayo Clinic (Other)
Overall Status
Completed
CT.gov ID
NCT02451488
Collaborator
(none)
8
1
2
18.2
0.4

Study Details

Study Description

Brief Summary

Randomized trial to determine if neo-adjuvant subcutaneous GM-CSF restores the host regional lymph node immunity

Condition or Disease Intervention/Treatment Phase
Phase 4

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
8 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Neoadjuvant GM-CSF Treatment and Modulation of Immune Cell Profile of the SLN in Melanoma
Study Start Date :
May 1, 2015
Actual Primary Completion Date :
Nov 4, 2016
Actual Study Completion Date :
Nov 4, 2016

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: GM-CSF
14 days in a dose of 125 µg/m^2
Other Names:
  • Leukine
  • Other: Standard of Care

    no neo-adjuvant therapy prior to surgical intervention

    Other: Standard of Care
    No neo-adjuvant therapy prior to surgical intervention

    Outcome Measures

    Primary Outcome Measures

    1. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Mayo Clinic in Rochester Rochester Minnesota United States 55905

    Sponsors and Collaborators

    • Mayo Clinic

    Investigators

    • Principal Investigator: James Jakub, MD, Mayo Clinic

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    James W. Jakub, PI, Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT02451488
    Other Study ID Numbers:
    • 14-005510
    First Posted:
    May 22, 2015
    Last Update Posted:
    Feb 10, 2020
    Last Verified:
    Jan 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title GM-CSF Standard of Care
    Arm/Group Description 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 no neo-adjuvant therapy prior to surgical intervention Standard of Care: No neo-adjuvant therapy prior to surgical intervention
    Period Title: Overall Study
    STARTED 4 4
    COMPLETED 4 4
    NOT COMPLETED 0 0

    Baseline Characteristics

    Arm/Group Title GM-CSF Standard of Care Total
    Arm/Group Description 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 no neo-adjuvant therapy prior to surgical intervention Standard of Care: No neo-adjuvant therapy prior to surgical intervention Total of all reporting groups
    Overall Participants 4 4 8
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    54.5
    (14.3)
    62.7
    (18.8)
    58.6
    (16.1)
    Sex: Female, Male (Count of Participants)
    Female
    2
    50%
    2
    50%
    4
    50%
    Male
    2
    50%
    2
    50%
    4
    50%
    Race and Ethnicity Not Collected (Count of Participants)
    Count of Participants [Participants]
    0
    0%
    Region of Enrollment (participants) [Number]
    United States
    4
    100%
    4
    100%
    8
    100%

    Outcome Measures

    1. Primary Outcome
    Title Th1/Th2 Normalized Gene Expression
    Description 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

    Outcome Measure Data

    Analysis Population Description
    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/Group Title GM-CSF Standard of Care
    Arm/Group Description 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 no neo-adjuvant therapy prior to surgical intervention Standard of Care: No neo-adjuvant therapy prior to surgical intervention
    Measure Participants 3 3
    T-bet (Th1)
    1.029
    0.119
    GATA3 (Th2)
    0.074
    0.192

    Adverse Events

    Time Frame 14 days
    Adverse Event Reporting Description Subjects receiving intervention will have adverse events (AEs) recorded during the 14 day course of self-administrated GM-CSF. Subjects will be provided a diary to record any AEs. Subjects will be provided a list of AEs and to call immediately for any grade 3 or high AEs. Grade I-II AEs will be logged into their diary. Diary will be collected the day of surgery. All-Cause Mortality, Serious, and Other (Not Including Serious) AEs were not monitored/assessed for the Standard of Care Arm/Group.
    Arm/Group Title GM-CSF Standard of Care
    Arm/Group Description 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 no neo-adjuvant therapy prior to surgical intervention Standard of Care: No neo-adjuvant therapy prior to surgical intervention
    All Cause Mortality
    GM-CSF Standard of Care
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/0 (NaN)
    Serious Adverse Events
    GM-CSF Standard of Care
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/0 (NaN)
    Other (Not Including Serious) Adverse Events
    GM-CSF Standard of Care
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/4 (0%) 0/0 (NaN)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. James Jakub
    Organization Mayo Clinic
    Phone 507-284-3629
    Email Jakub.James@mayo.edu
    Responsible Party:
    James W. Jakub, PI, Mayo Clinic
    ClinicalTrials.gov Identifier:
    NCT02451488
    Other Study ID Numbers:
    • 14-005510
    First Posted:
    May 22, 2015
    Last Update Posted:
    Feb 10, 2020
    Last Verified:
    Jan 1, 2020