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

NCT01363206 | Completed Phase 2

• 3 other identifiers: GIPIBMS 184051Genzyme LEU001
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Malignant Melanoma, Metastatic

Keywords

Melanoma; GM-CSF; Ipilimumab; Immunologic Response

Outcome Measures

Primary Outcomes (1)

• Disease control rate at 24 weeks as defined by the immune-related Response Criteria (irRC)

  Disease control rate will be measured at 24 weeks from the start date of protocol therapy using the immune-related Response Criteria (irRC)

  24 weeks

Secondary Outcomes (7)

• Assessment of immune activation as determined in the Companion Protocol

  Three years

• 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.

  Four years

• Overall Survival (OS)

  Four years

• Objective Response Rate (RR)

  Two years

• Time to Objective response

  Three years

Study Arms (1)

Single arm open label

EXPERIMENTAL

GM-CSF and Ipilimumab

Biological: Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF); Biological: Ipilimumab

Interventions

Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) BIOLOGICAL

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.

Also known as: Leukine, Sargramostim

Single arm open label

Ipilimumab BIOLOGICAL

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.

Also known as: Yervoy, Anti-CTLA-4 Monoclonal Antibody

Single arm open label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically confirmed, (surgically incurable or unresectable) stage III or IV metastatic malignant melanoma.
• Prior systemic therapy for metastatic disease is permitted but not required
• A minimum of 1 measurable lesion according to irRC criteria.
• ECOG performance status of 0-2.
• Men and women, age ≥ 18 years.
• 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

You may not qualify if:

• Brain metastases that are not treated and not stable for at least 1 month.
• History of or known spinal cord compression, or carcinomatous meningitis, or evidence of symptomatic brain or leptomeningeal disease on screening CT or MRI scan.
• 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.
• 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).
• 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.
• 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.
• Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to one month prior to or after any dose of ipilimumab.
• A history of prior treatment with ipilimumab, CD137 agonist, CTLA-4 inhibitor or agonist; GM-CSF, or monoclonal antibody.
• 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.
• 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
• Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious) illness
• 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

Sponsors & Collaborators

• Lynn E. Spitler, MD: lead
• University of California, San Francisco: collaborator

Study Sites (2)

Northern Californai Melanoma Center, St. Mary's Medical Center

San Francisco, California, 94117, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Related Publications (5)

• Hodi FS, O'Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC, Akerley W, van den Eertwegh AJ, Lutzky J, Lorigan P, Vaubel JM, Linette GP, Hogg D, Ottensmeier CH, Lebbe C, Peschel C, Quirt I, Clark JI, Wolchok JD, Weber JS, Tian J, Yellin MJ, Nichol GM, Hoos A, Urba WJ. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010 Aug 19;363(8):711-23. doi: 10.1056/NEJMoa1003466. Epub 2010 Jun 5.

  PMID: 20525992 BACKGROUND

• Spitler LE, Grossbard ML, Ernstoff MS, Silver G, Jacobs M, Hayes FA, Soong SJ. Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor. J Clin Oncol. 2000 Apr;18(8):1614-21. doi: 10.1200/JCO.2000.18.8.1614.

  PMID: 10764421 BACKGROUND

• Hoos A, Eggermont AM, Janetzki S, Hodi FS, Ibrahim R, Anderson A, Humphrey R, Blumenstein B, Old L, Wolchok J. Improved endpoints for cancer immunotherapy trials. J Natl Cancer Inst. 2010 Sep 22;102(18):1388-97. doi: 10.1093/jnci/djq310. Epub 2010 Sep 8.

  PMID: 20826737 BACKGROUND

• Kavanagh B, O'Brien S, Lee D, Hou Y, Weinberg V, Rini B, Allison JP, Small EJ, Fong L. CTLA4 blockade expands FoxP3+ regulatory and activated effector CD4+ T cells in a dose-dependent fashion. Blood. 2008 Aug 15;112(4):1175-83. doi: 10.1182/blood-2007-11-125435. Epub 2008 Jun 3.

  PMID: 18523152 BACKGROUND

• Cham J, Zhang L, Kwek S, Paciorek A, He T, Fong G, Oh DY, Fong L. Combination immunotherapy induces distinct T-cell repertoire responses when administered to patients with different malignancies. J Immunother Cancer. 2020 May;8(1):e000368. doi: 10.1136/jitc-2019-000368.

  PMID: 32376721 DERIVED

Related Links

• This describes the site where the clinical trial is being conducted.

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis

Interventions

Colony-Stimulating Factors; Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim; Ipilimumab

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins

Study Officials

• Lynn E. Spitler, M.D.

  Northern California Melanoma Center, St. Mary's Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Director

Study Record Dates

• First Submitted: May 27, 2011
• First Posted: June 1, 2011
• Study Start: May 1, 2011
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2015
• Last Updated: March 19, 2020

Record last verified: 2020-03

Locations

US (2)