patients with advanced melanoma and spontaneous preexisting immune response to NY-ESO-1. MedDRA version: 17.0 Level: HLT Classification code 10027156 Term: Skin melanomas (excl ocular) System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Yervoy
Product Name: BMS-734016/MDX-010/Ipilimumab
Product Code: BMS-734016
Pharmaceutical Form: Concentrate for solution for infusion
CAS Number: 477202-00-9
Current Sponsor code: BMS-734
Sponsors
Universitätsklinikum Heidelberg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ? Signed Written Informed Consent must be obtained before performing protocol-related procedures that are not part of standard patient care. ? Target Population 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. (see Appendix 7). Cut-off calculation: Sera from 50 healthy donors are measured in triplicates against the GST-NY-ESO-1 fusion protein and the mean as well as the standard deviation are determined. ? The cut-off represents the mean of the means of all measured samples plus 3 times the standard deviation of the mean of the means. . ? 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; ? Have the complete set of baseline (i.e., screening) digital images of lesions and radiographic images, including, but not limited to: chest, abdomen, pelvis, and other soft tissue scans. All images must be of adequate quality; ? 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 (except subjects with Gilbert’s Syndrome who must have a total bilirubin less than 3.0 mg/dL). Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study [and for up to 26 weeks after the last dose of investigational product] in such a manner that the risk of pregnancy is minimized. Suggested precautions should be used to minimize the risk of pregnancy for at least 1 month before dosing, and while women are on study and for up to 26 weeks after last dose of study drug; 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 menopause is defined as • Amenorrhea = 12 consecutive months without another cause, or • For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL. Women who are using oral contraceptives, other hormonal contraceptives (vaginal products, skin patches, or implanted or injectable products), or mechanical products such as an intrauterine device or barrier methods (diaphragm, condoms, spermicides) to prevent pregnancy, or are practicing abstinence or where their partner is sterile (eg, vasectomy) should be considered to be of childbearing potential. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 72 hours prior to the start of investigational product. Men must be willing and able to use an acceptable method of birth control fo
Exclusion criteria
Exclusion criteria: Women who are pregnant or breastfeeding Target Disease Exceptions 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. Medical History and Concurrent Diseases 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. Laboratory Test Findings Inadequate hematologic function defined by an absolute neutrophil count (ANC) 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. Prohibited Treatments and/or Therapies Chronic use of immunosuppressants and/or systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses). However, use of corticosteroids are allowed for treating irAEs, or adrenal insufficiencies; 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. Further Exclusion Criteria 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 . Eligibility criteria for this study have been carefully considered to ensure the safety of the study subjects and to ensure that the results of the study can be used. It is imperative that subjects fully meet all eligibility criteria. No exceptions will be granted.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Immune-related Disease Control Rate irDCR (irCR, irPR, irSD) according to the immune-related response criteria (see Appendix 1) in patients with spontaneous preexisting NY-ESO-1 immune response treated with ipilimumab.;Timepoint(s) of evaluation of this end point: at week 12, 24, 36, 48;Secondary Objective: Immune-related median progression-free survival (PFS) in patients with spontaneous preexisting immune response to NY-ESO-1 treated with ipilimumab Overall survival (OS) rate at 12 months after the first study treatment in patients with spontaneous preexisting immune response to NY-ESO-1 treated with ipilimumab Safety / toxicity according to the CTC Criteria (Version 4.0);Primary end point(s): The primary endpoint is the immune-related Disease Controle Rate (irDCR) as defined in Section 2.1.) For patients without irDCR evaluation at the end of treatment (or within the observation period in case of discontinuation of the planned treatment) it is assumed that no irDCR is achieved. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Disease Control Rate (CR, PR, SD) according to RESIST Criteria -Progression free survival (PFS) -Overall survival (OS) ;Timepoint(s) of evaluation of this end point: OS: after 12 months | — |
Countries
Germany
Contacts
Public ContactPrincipal Investigator
NCT Heidelberg
Outcome results
None listed