Ipilimumab in Patients With Advanced Melanoma and Spontaneous Preexisting Immune Response to NY-ESO-1 (CTLA4 NY-ESO-1)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2013 by National Center for Tumor Diseases, Heidelberg
Sponsor:
Collaborator:
University Hospital Heidelberg
Information provided by (Responsible Party):
National Center for Tumor Diseases, Heidelberg
ClinicalTrials.gov Identifier:
NCT01216696
First received: September 27, 2010
Last updated: September 13, 2013
Last verified: September 2013
  Purpose

This is an Open-label, single-arm, phase II study of ipilimumab in patients with spontaneous preexisting immune response to NY-ESO-1.

Preclinical data suggest, that CTLA-4 blockade enhances polyfunctional T cell responses in patients with melanoma. Thus patients with immunological response to NY-ESO-1 might benefit from an anti CTLA-4 treatment.

Eligible patients will receive 10 mg/kg ipilimumab every 3 weeks during a 10-week induction period, followed by a radiological assessment in week 12. Patients with clinical benefit (partial response, complete response or stable disease according to the immune-related response criteria) will continue with an ipilimumab administration every 3 months starting at week 24 up to week 48 until the end of the study or until disease progression,toxicities requiring discontinuation


Condition Intervention Phase
Metastatic Melanoma
Drug: 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: Phase II Trial of Ipilimumab in Patients With Advanced Melanoma and Spontaneous Preexisting Immune Response to NY-ESO-1

Resource links provided by NLM:


Further study details as provided by National Center for Tumor Diseases, Heidelberg:

Primary Outcome Measures:
  • Disease Control Rate according to immune-related response criteria [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To determine the efficacy of ipilimumab in patients with stage III and stage IV malignant melanoma and spontaneous preexisting immune response to NY-ESO-1.


Secondary Outcome Measures:
  • Progression-free survival according to the immune-related response criteria [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To document progression-free survival (PFS) in patients with evaluable or measurable disease after receiving ipilimumab according to the immune-related response criteria (irRC),

  • Overall Survival at 12 months [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    To document overall-survival (OS) rate at 12 months after the first study treatment in patients receiving ipilimumab.

  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
    To assess the safety profile of ipilimumab in patients with malignant melanoma stage III and IV and sponanteous preexisting immune response to NY-ESO-1.


Estimated Enrollment: 25
Study Start Date: November 2010
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: ipilimumab
    Eligible patients will receive 10 mg/kg ipilimumab every 3 weeks during a 10-week induction period, followed by a radiological assessment in week 12. Patients with clinical benefit will continue with an ipilimumab administration every 3 months starting at week 24 up to week 48 until the end of the study or until disease progression, toxicities requiring discontinuation , withdrawal of consent,pregnancy, death or lost to follow up whichever occurs first.
  Eligibility

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

Inclusion Criteria:

  • Histologic diagnosis of malignant melanoma; unresectable Stage III melanoma or Stage IV melanoma; Measurable/evaluable disease (as per mWHO criteria), within 28 days before first dose of study drug;
  • Preexisting spontaneous immune response to NY-ESO-1, defined by positive results in ELISA above a prespecified cut-off value.
  • Previously treated or untreated metastatic melanoma. The previous treatment must have been finished at least 28 days before the first ipilimumab administration. Patients must have recovered from any acute toxicity associated with prior therapy
  • Life expectancy of ≥ 16 weeks;
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
  • Men and women, ages 18 and above.
  • Ability of subject to understand character and individual consequences of the clinical trial
  • Required values for initial laboratory tests:

    • WBC ≥ 2000/μL
    • ANC ≥ 1000/μL
    • Platelets ≥ 100 x 103/μL
    • Hemoglobin ≥ 9 g/dL (may be transfused)
    • Creatinine ≤ 2 x ULN
    • AST/ALT ≤ 2.5 x ULN for subjects without liver metastasis≤ 5 x ULN for subjects with liver metastasis
    • Bilirubin ≤ 2.0 x ULN
  • Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study

Exclusion Criteria:

  • Brain Metastasis, unless previously treated, off steroids for at least 4 weeks and considered to be stable (eg, no progression of the treated lesion);
  • Primary ocular or mucosal melanoma
  • Prior malignancy active within the previous 5 years except for locally curable cancers that have been adequately treated, such as basal or squamous cell skin cancer.
  • Autoimmune disease: subjects with a documented history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease are excluded from this study as are subjects with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]). Subjects with motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome) are excluded from this study
  • Any underlying medical or psychiatric 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.
  • Previous participation with a NY-ESO 1 derived vaccination study.
  • Inadequate hematologic function defined by an absolute neutrophil count (ANC) < 1,000/mm3, a platelet count < 100,000/mm3, or a hemoglobin level < 9 g/dL;
  • Inadequate hepatic function defined by a total bilirubin level > 2.0 x ULN except subjects with Gilbert's Syndrome, who must have a total bilirubin < 3.0 ULN. AST and ALT levels ≥ 2.5 times the ULN, or ≥ 5 times the ULN if liver metastases are present;
  • Inadequate renal function defined by a serum creatinine level ≥ 2.0 times the ULN, or inadequate creatinine clearance defined as less than 50 mL/min;
  • Positive tests for HIV, Hepatitis B, and Hepatitis C. If positive results are not indicative of true active or chronic infection, the patient can enter the study after discussion and agreement with the investigator and the Medical Monitor.
  • Chronic use of immunosuppressants and/or systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses).
  • Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 4 weeks prior to or after any dose of ipilimumab);
  • Prior treatment with a CD137 agonist, ipilimumab or other CTLA-4 inhibitor.
  • Prisoners or subjects who are involuntarily incarcerated
  • Participation in other clinical trials or observation period of competing trials, respectively during the last 30 days before the first application of the investigational agent .
  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: NCT01216696

Contacts
Contact: Dirk Jaeger, MD +49-6221-56-4801 Dirk.Jaeger@nct-heidelberg.de

Locations
Germany
NCT, Dep. of Medical Oncology Recruiting
Heidelberg, Germany, 69120
Sponsors and Collaborators
National Center for Tumor Diseases, Heidelberg
University Hospital Heidelberg
Investigators
Principal Investigator: Dirk Jäger, MD NCT Heidelberg, Dep. of Medical Oncology
  More Information

No publications provided

Responsible Party: National Center for Tumor Diseases, Heidelberg
ClinicalTrials.gov Identifier: NCT01216696     History of Changes
Other Study ID Numbers: NCT-2009-11-02-53
Study First Received: September 27, 2010
Last Updated: September 13, 2013
Health Authority: Germany: Paul-Ehrlich-Institut

Keywords provided by National Center for Tumor Diseases, Heidelberg:
ipilimumab
melanoma
NY-ESO-1

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 August 21, 2014