Granulocyte Macrophage-Colony Stimulating Factor and Ipilimumab as Therapy in Melanoma (GIPI)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
University of California, San Francisco
Information provided by (Responsible Party):
Lynn E. Spitler, MD, Northern California Melanoma Center
ClinicalTrials.gov Identifier:
NCT01363206
First received: May 27, 2011
Last updated: March 6, 2014
Last verified: March 2014
  Purpose

The study is an open-label, single arm single Center Phase II study to evaluate the safety and efficacy of the combination of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF, Leukine) and Ipilimumab (Yervoy) as therapy for patients with unresectable metastatic malignant melanoma.


Condition Intervention Phase
Malignant Melanoma, Metastatic
Biological: Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
Biological: Ipilimumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: GM-CSF and Ipilimumab as Therapy in Metastatic Melanoma, a Phase II Study

Resource links provided by NLM:


Further study details as provided by Northern California Melanoma Center:

Primary Outcome Measures:
  • Disease control rate at 24 weeks as defined by the immune-related Response Criteria (irRC) [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Disease control rate will be measured at 24 weeks from the start date of protocol therapy using the immune-related Response Criteria (irRC)


Secondary Outcome Measures:
  • Assessment of immune activation as determined in the Companion Protocol [ Time Frame: Three years ] [ Designated as safety issue: No ]
    Blood will be drawn for immunologic testing at each patient visit.

  • Duration of disease control defined as the time from the date of the first treatment dose to the date of first documentation of disease progression as defined by irRC. [ Time Frame: Four years ] [ Designated as safety issue: No ]
    According to irRC criteria, increase in the size of target lesions or the appearance of new lesions within 12 weeks of the initiation of ipilimumab therapy does not necessarily represent disease progression (as they would using conventional RECIST criteria).

  • Overall Survival (OS) [ Time Frame: Four years ] [ Designated as safety issue: No ]
    Overall Survival (OS) is defined as the time from the date of the first treatment dose to date of death due to any cause. In the absence of confirmation of death, survival time will be censored at the last date the patient was known to be alive.

  • Objective Response Rate (RR) [ Time Frame: Two years ] [ Designated as safety issue: No ]
    The Objective Response Rate (RR) at any time during the 2 years of study treatment will be evaluated in this study using the immune related Response Criteria (irRC).

  • Time to Objective response [ Time Frame: Three years ] [ Designated as safety issue: No ]
    The Time to Objective response is defined as the time from the date of the first treatment dose to the date of first documentation of disease response.

  • Duration of objective response (CR or PR) [ Time Frame: Four years ] [ Designated as safety issue: No ]
    The duration of objective response (CR or PR) will be measured from the date the response was first documented to the date of progression or death due to progressive disease, whichever occurs first.

  • Safety of the combination [ Time Frame: Three years ] [ Designated as safety issue: Yes ]
    The safety of the combination as defined by the NCI CTCAE criteria, Version 4.0.


Estimated Enrollment: 43
Study Start Date: May 2011
Estimated Study Completion Date: May 2015
Estimated Primary Completion Date: May 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm open label
GM-CSF and Ipilimumab
Biological: Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)
GM-CSF will be administered subcutaneously daily for 14 days in a dose of 125 µg/m2 beginning on D1 of each 21-day cycle for 8 cycles until month 6. Maintenance therapy will begin at month 6 and will consist 14 days of GM-CSF repeated every 3 months for up to 2 years or until disease progression, whichever occurs first.
Other Names:
  • Leukine
  • Sargramostim
Biological: Ipilimumab
Patients will be treated with 4 courses of ipilimumab administered every 3 weeks intravenously in a dose of 10 mg/kg, with appropriate stopping/de-escalation rules. Maintenance therapy will begin at month 6 and will consist of ipilimumab in the same dose administered at the end of cycle 4 repeated every 3 months for up to 2 years or until disease progression, whichever occurs first.
Other Names:
  • Yervoy
  • Anti-CTLA-4 Monoclonal Antibody

Detailed Description:

The study is an open-label, single arm single Center Phase II study to evaluate the safety and efficacy of the combination of Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF, Leukine) and Ipilimumab (Yervoy) as therapy for patients with unresectable metastatic malignant melanoma. The patient sample will be approximately 43 evaluable individuals, males and females 18 years of age or older with measurable metastatic melanoma. Immunologic testing will be done to evaluate correlation with clinical outcome.

Patients will be treated with 4 courses of GM-CSF and ipilimumab administered every 3 weeks. GM-CSF will be administered subcutaneously daily for 14 days in a dose of 125 µg/m2 beginning on D1 of each 21-day cycle. Ipilimumab intravenously in a dose of 10 mg/kg, with appropriate stopping/de-escalation rules. After the initial 3 months (4 cycles) of treatment, GM-CSF administration will continue for 4 additional cycles on the same schedule and dose without ipilimumab for 14 days every 21 days until month 6. Maintenance therapy will begin at month 6 and will consist of ipilimumab in the same dose administered at the end of cycle 4 combined with 14 days of GM-CSF. Administration of this combination will be repeated every 3 months for up to 2 years or until disease progression, whichever occurs first. During the maintenance phase, GM-CSF will only be administered for 14 days in conjunction with ipilimumab and will not be administered in the intervening time period.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Histologically confirmed, (surgically incurable or unresectable) stage III or IV metastatic malignant melanoma.
  2. Prior systemic therapy for metastatic disease is permitted but not required
  3. A minimum of 1 measurable lesion according to irRC criteria.
  4. ECOG performance status of 0-2.
  5. Men and women, age ≥ 18 years.
  6. Adequate hematologic, renal and liver function as defined by laboratory values performed within 14 days prior to initiation of dosing.

    • WBC ≥ 2000/uL
    • Absolute neutrophil count (ANC) ≥ 1000/uL
    • Platelet count ≥ 50,000/uL
    • Hemoglobin ≥ 8.0 g/dL
    • Serum creatinine ≤ 3.0 x upper limit of normal
    • Total serum bilirubin ≤ 3.0 x upper limit of normal (except patients with Gilbert's Syndrome, who must have a total bilirubin less than 3.0 mg/dL
    • LDH ≤ 4 times upper limit of laboratory normal
    • Serum aspartate transaminase (ASAT/SGOT) or serum alanine transaminase (ALAT/SGPT) ≤ 2.5 times upper limit of laboratory normal for patients without liver metastases
    • Alkaline phosphatase ≤ 2.5 times upper limit of normal, unless bone metastasis is present in the absence of liver metastases
  7. No active or chronic infection with HIV, Hepatitis B, or Hepatitis C
  8. Patients must have recovered from effects of major surgery.
  9. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 8 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, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal. Post-menopausal is defined as:

  • Amenorrhea ≥ 12 consecutive months without another cause, or
  • For women with irregular menstrual periods and taking hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level ≥ 35mIU/mL].

Exclusion Criteria:

  1. Brain metastases that are not treated and not stable for at least 1 month.
  2. History of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan.
  3. Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix.
  4. Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis (e.g., Wegener's Granulomatosis), motor neuropathy considered of autoimmune origin (e.g. Guillain-Barré Syndrome).
  5. Any underlying medical condition, which in the opinion of the Investigator, will make the administration of study drug hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea.
  6. Psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before trial entry.
  7. Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab.
  8. A history of prior treatment with ipilimumab, CD137 agonist, CTLA-4 inhibitor or agonist; GM-CSF, or monoclonal antibody.
  9. Concomitant therapy with any of the following: IL-2, interferon or other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; or chronic use of systemic corticosteroids.
  10. Women of child-bearing potential (WOCBP) who:

    • are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for at least 8 weeks after cessation of study drug, or
    • have a positive pregnancy test at baseline, or
    • are pregnant or breastfeeding
  11. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
  12. Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 8 weeks after study drug is stopped
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01363206

Locations
United States, California
Northern Californai Melanoma Center, St. Mary's Medical Center
San Francisco, California, United States, 94117
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Lynn E. Spitler, MD
University of California, San Francisco
Investigators
Principal Investigator: Lynn E. Spitler, M.D. Northern California Melanoma Center, St. Mary's Medical Center
  More Information

Additional Information:
Publications:
Responsible Party: Lynn E. Spitler, MD, Director, Northern California Melanoma Center
ClinicalTrials.gov Identifier: NCT01363206     History of Changes
Other Study ID Numbers: GIPI, BMS 184051, Genzyme LEU001
Study First Received: May 27, 2011
Last Updated: March 6, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Northern California Melanoma Center:
Melanoma
GM-CSF
Ipilimumab
Immunologic Response

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas

ClinicalTrials.gov processed this record on September 30, 2014