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

• ClinicalTrials.gov Identifier: NCT02451488
• Recruitment Status: Completed
• First Posted: May 22, 2015
• Results First Posted: February 10, 2020
• Last Update Posted: February 10, 2020
• Sponsor: Mayo Clinic
• Information provided by (Responsible Party): James W. Jakub, Mayo Clinic

Tracking Information

• First Submitted Date: May 18, 2015
• First Posted Date: May 22, 2015
• Results First Submitted Date: December 15, 2019
• Results First Posted Date: February 10, 2020
• Last Update Posted Date: February 10, 2020
• Study Start Date: May 2015
• Actual Primary Completion Date: November 4, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 29, 2020)

Th1/Th2 Normalized Gene Expression [ Time Frame: 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.

Original Primary Outcome Measures (submitted: May 19, 2015)

Th1/Th2 ratio [ Time Frame: Approximately 19 days after enrollment ]

Subjects will undergo sentinel lymph node (SLN) biopsy and the SLN will be sent to pathology. 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).

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Neoadjuvant Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) in Cutaneous Stage L-lll Melanoma
• Official Title: Neoadjuvant GM-CSF Treatment and Modulation of Immune Cell Profile of the SLN in Melanoma
• 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.
• Study Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Melanoma

Intervention

• Drug: GM-CSF
  14 days in a dose of 125 µg/m^2
  Other Name: Leukine
• Other: Standard of Care
  No neo-adjuvant therapy prior to surgical intervention

Study Arms

• 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.
  Intervention: Drug: GM-CSF
• Standard of Care
  no neo-adjuvant therapy prior to surgical intervention
  Intervention: Other: Standard of Care

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 29, 2020): 8
• Original Estimated Enrollment (submitted: May 19, 2015): 20
• Actual Study Completion Date: November 4, 2016
• Actual Primary Completion Date: November 4, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02451488
• Other Study ID Numbers: 14-005510
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No
• Plan Description: data will not be shared

• Responsible Party: James W. Jakub, Mayo Clinic
• Study Sponsor: Mayo Clinic
• Collaborators: Not Provided

Investigators

• Principal Investigator: James Jakub, MD; Mayo Clinic

• PRS Account: Mayo Clinic
• Verification Date: January 2020