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Ipilimumab With or Without Sargramostim in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed By Surgery

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT01134614
First received: April 27, 2010
Last updated: December 6, 2013
Last verified: December 2013

April 27, 2010
December 6, 2013
December 2010
March 2013   (final data collection date for primary outcome measure)
Overall survival [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
The method of Kaplan- Meir will be used.
Overall survival [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01134614 on ClinicalTrials.gov Archive Site
  • Progression-free survival [ Time Frame: From randomization to disease progression or death without progression, assessed up to 5 years ] [ Designated as safety issue: No ]
    The method of Kaplan- Meir will be used.
  • Response rate using RECIST [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    The Kappa statistics which measures the degree of agreement between the RECIST-based response and irRC will be estimated. McNemar's test will be used to evaluate the agreement between irRC and RECIST-based clinical response.
  • Safety and tolerability assessed using NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    Incidence data of specific toxicity type as well overall worst degree toxicity data will be summarized and compared between the two arms.
  • Progression-free survival [ Designated as safety issue: No ]
  • Response rate [ Designated as safety issue: No ]
  • Safety and tolerability [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Ipilimumab With or Without Sargramostim in Treating Patients With Stage III or Stage IV Melanoma That Cannot Be Removed By Surgery
A Phase II Trial of GM-CSF Protein Plus Ipilimumab in Patients With Advanced Melanoma

This randomized phase II trial is studying how well giving ipilimumab with or without sargramostim works in treating patients with stage III or stage IV melanoma that cannot be removed by surgery. Monoclonal antibodies, such as ipilimumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Colony-stimulating factors, such as sargramostim (GM-CSF), may increase the number of immune cells found in bone marrow or peripheral blood and may help the immune system recover from the side effects of treatment. It is not yet know whether giving ipilimumab together with GM-CSF is more effective than ipilimumab alone in treating melanoma.

PRIMARY OBJECTIVES:

I. To evaluate the overall survival of patients with advanced melanoma treated with ipilimumab with versus without sargramostim.

SECONDARY OBJECTIVES:

I. To evaluate the progression-free survival of patients treated with these regimens.

II. To evaluate the response rate in patients treated with these regimens. III. To evaluate the safety and tolerability of these regimens in these patients.

IV. To explore prospectively the utility of immune-related response criteria (irRC) of patients receiving ipilimumab.

OUTLINE: This is a multicenter study. Patients are stratified according to disease stage (unresectable vs M1a/1b vs M1c) and prior therapy (none vs interferon vs one investigational therapy). Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive induction therapy comprising ipilimumab IV over 90 minutes on day 1 and sargramostim subcutaneously (SC) once daily on days 1-14. Treatment repeats every 21 days for 4 courses. Patients with responsive or stable disease then receive maintenance therapy comprising ipilimumab IV over 90 minutes on day 1 and sargramostim SC once daily on days 1-14. Treatment with ipilimumab repeats every 12 weeks and treatment with sargramostim repeats every 21 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive induction therapy comprising ipilimumab as in arm I. Patients with responsive or stable disease then receive maintenance therapy comprising ipilimumab IV as in arm I. Courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study therapy, patients are followed up every 3-6 months for up to 5 years.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Recurrent Melanoma
  • Stage III Melanoma
  • Stage IV Melanoma
  • Biological: ipilimumab
    Given IV
    Other Names:
    • anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
    • MDX-010
    • MDX-CTLA-4
    • monoclonal antibody CTLA-4
  • Biological: sargramostim
    Given SC
    Other Names:
    • GM-CSF
    • Leukine
    • Prokine
  • Experimental: Arm I (ipilimumab and sargramostim)
    Patients receive induction therapy comprising ipilimumab IV over 90 minutes on day 1 and sargramostim SC once daily on days 1-14. Treatment repeats every 21 days for 4 courses. Patients with responsive or stable disease then receive maintenance therapy comprising ipilimumab IV over 90 minutes on day 1 and sargramostim SC once daily on days 1-14. Treatment with ipilimumab repeats every 12 weeks and treatment with sargramostim repeats every 21 days in the absence of disease progression or unacceptable toxicity.
    Interventions:
    • Biological: ipilimumab
    • Biological: sargramostim
  • Experimental: Arm II (ipilimumab)
    Patients receive induction therapy comprising ipilimumab as in arm I. Patients with responsive or stable disease then receive maintenance therapy comprising ipilimumab IV as in arm I. Courses repeat every 12 weeks in the absence of disease progression or unacceptable toxicity.
    Intervention: Biological: ipilimumab
Hodi FS, Lee S, McDermott DF, Rao UN, Butterfield LH, Tarhini AA, Leming P, Puzanov I, Shin D, Kirkwood JM. Ipilimumab plus sargramostim vs ipilimumab alone for treatment of metastatic melanoma: a randomized clinical trial. JAMA. 2014 Nov 5;312(17):1744-53. doi: 10.1001/jama.2014.13943.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
220
Not Provided
March 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Histologically confirmed metastatic melanoma

    • Unresectable stage III or IV disease
    • For unknown primary disease, diagnosis of metastatic disease by cytology FNA is not acceptable
  • Measurable disease
  • No more than 1 prior investigational therapy or systemic therapeutic regimen*, including any of the following:

    • Chemotherapy
    • Biological therapy
    • Biochemotherapy
    • Investigational treatment
  • No CNS metastases
  • ECOG performance status 0-1
  • WBC ≥ 2,000/μL
  • ANC ≥ 1,500/μL
  • Platelet count ≥ 100,000/μL
  • Hemoglobin ≥ 8 g/dL
  • Creatinine ≤ 3.0 times upper limit of normal (ULN)
  • AST and ALT ≤ 2.5 times ULN
  • Bilirubin ≤ 3.0 times ULN (total bilirubin < 3.0 mg/dL for patients with Gilbert syndrome)
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception during and for up to 12 weeks after completion of study
  • No HIV infection
  • No active infection with hepatitis B virus
  • No active or chronic infection with hepatitis C virus
  • No other malignancy with the past 2 years except adequately treated and cured basal cell or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
  • No history of autoimmune disease, including any of the following:

    • Inflammatory bowel disease
    • Symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis[scleroderma])
    • Systemic lupus erythematosus
    • Autoimmune vasculitis (e.g., Wegener granulomatosis)
    • Motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre syndrome and myasthenia gravis)
  • Patients with a history of autoimmune thyroiditis are eligible if their current thyroid disorder is treated and stable with replacement or other medical therapy
  • No underlying medical or psychiatric condition that, in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea
  • No concurrent medical condition requiring the use of systemic steroids
  • No other concurrent CTLA-4 inhibitor or agonist or CD137 agonist
  • At least 4 weeks since prior and no concurrent therapy with any of the following:

    • Aldesleukin (IL-2)
    • Interferon
    • Non-study immunotherapy regimens
    • Cytotoxic chemotherapy
    • Immunosuppressive agents
    • Other investigational therapies
    • Chronic use of systemic corticosteroids

      • Concurrent inhaled or topical steroids allowed
      • Concurrent physiologic replacement doses of corticosteroids allowed
  • No prior non-oncology vaccine therapy for the prevention of infectious disease within the past 28 days or after any dose of ipilimumab
  • No prior ipilimumab, CD137agonist, or CTLA-4 inhibitor or agonist
  • No other systemic or local anticancer medications
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01134614
NCI-2011-02039, NCI-2011-02039, CDR0000671238, E1608, E1608, U10CA021115
Not Provided
National Cancer Institute (NCI)
National Cancer Institute (NCI)
Not Provided
Principal Investigator: Frank Hodi Eastern Cooperative Oncology Group
National Cancer Institute (NCI)
December 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP