Stage III, IV metastatic advanced melanoma
Conditions
Interventions
Product Name: Ipilimumab
Product Code: BMS-734016 / MDX010
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: IPILIMUMAB
CAS Number: 477202-00-9
Current Sponsor code: BMS-734016 / MDX010
Sponsors
Bristol-Myers Squibb International Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patients eligible for this study must represent one of the three patient populations described in Section 3.2 of the Protocol and meet the inclusion/exclusion criteria detailed below. Group C (except Group C Survival Follow-Up Only) patients must meet Inclusion Criteria 1, 2, and 3 and Exclusion Criteria 1 and 2. Group C Survival Follow-Up Only patients must meet Inclusion Criteria 1, 2, 3 and Exclusion Criterion 2. 1. Willing and able to give written informed consent; Target population 2. Diagnosis of advanced melanoma; 3. Prior treatment in one of the following studies: CA184008, CA184-022, CA184007, CA184004, MDX010-08 or MDX010-15; and meets criteria for Group A, B or C (see Section 3.2.) 4. Accessible for treatment and Follow-Up; 5. All patients entering the study as Group A to receive Re-Induction must have their case discussed with a BMS Medical Monitor prior to enrollment in the companion study; 6. Patients who have not experienced IBE related to ipilimumab, or patients who have experienced a select IBE related to ipilimumab that has completely resolved with immunosuppressive therapy or controlled with hormone therapy (* see below for IBEs eligible for consideration, also refer to Section 3.2.2 for definition of select reversible IBEs): * List of IBEs eligible for consideration: a) Reversible autoimmune hepatitis b) Medically manageable endocrinopathy c) Reversible dermatological toxicity 7. Have the complete set of baseline (i.e., Screening) images of lesions and radiographic images, including, but not limited to: brain, chest, abdomen pelvis and bone scans (bone scan only as applicable). All images must be of adequate quality; 8. Life expectancy =16 weeks; 9. ECOG performance status of 0 or 1 (Group A patients only, refer to Appendix 3); 10. Required values for initial laboratory tests (Group A patients only): • WBC = 2000/uL • ANC = 1000/uL • Platelets = 50 x 10³/uL • Hemoglobin = 8 g/dL • Creatinine = 3.0 x ULN • AST/ALT = 2.5 x ULN for patients without liver metastasis ; = 5 x ULN for patients with liver metastasis • Bilirubin = 3.0 x ULN, (except patients with Gilbert’s Syndrome, who must have a total bilirubin less than 3.0 mg/dL); 11. No active or chronic infection with HIV, Hepatitis B or Hepatitis C; Age and Sex 12. Men and women =18 years of age (or, = 16, if allowable per local regulatory authority); Women of childbearing potential (WOCBP) must be using a highly effective method(s) of contraception (failure rate of less than 1% per year) to avoid pregnancy throughout the study and for up to 12 weeks after the last date of study treatment in such a manner that the risk of pregnancy is minimized. 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 study medication and within 24 hours prior to each dose. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: For Group A, B, and C patients: 1) Prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist, except for ipilimumab; 2) Prisoners or patients who are compulsorily detained (involuntarily incarcerated) for treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be enrolled in this study. For Group A and Group B patients: Sex and Reproductive Status 3) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the study; 4) Women who are pregnant or breastfeeding; 5) Women with a positive pregnancy test on enrollment or prior to study drug administration; 6) Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. The investigator shall review contraception methods and the time period that contraception must be followed. Men that are sexually active with WOCBP must follow instructions for birth control when the half life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 12 weeks after dosing has been completed; Target Disease Exceptions 7) Primary ocular melanoma; Medical History and Concurrent Diseases 8) Any underlying medical or psychiatric condition or acute infection, 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) or efficacy data (such as active lung infection that interferes with response assessments); 8a) 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 (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [eg, Wegener’s Granulomatosis]). Subjects with motor neuropathy considered of autoimmune origin (eg, Guillain-Barré Syndrome) are excluded from this study. Prohibited Therapies and/or Medications 9) Concomitant therapy with any anti-cancer agent (for up to 30 days prior to 1st dose of ipilimumab in this study and except as defined in Section 6.2.8.5), immunosuppressive agents (for up to 30 days prior to 1st dose of ipilimumab in this study), surgery or radiotherapy (except as defined in Sections 6.2.8.3 and 6.2.8.4) (for up to 30 days prior to 1st dose of ipilimumab in this study); and chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses and for up to 30 days prior to 1st dose of ipilimumab in this study). 10) Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 4 weeks prior to or after any dose of ipilimumab); 11) Treatment with other investigational products within the last 4 weeks prior to or during this study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To monitor the safety of ipilimumab (MDX-010) administered either as Re-Induction (10 mg/kg or 3 mg/kg) or as Maintenance therapy (0.3, 3 or 10 mg/kg) in this ipilimumab (MDX-010) clinical study.;Secondary Objective: For all patients: 1)OS from 1st dose of ipi. in parent study 2)survival rate at 1 year from 1st dose of ipi. in parent study 3)monitor patients (except in Group C Survival Follow-Up Only) who experience irAEs after ipi. treatment For patients receiving Re-Induction in this study at time of disease progression, following clinical benefit (SD, PR or CR) after ipi. treatment: 4)Best ORR following 1st Re-Induction in this study 5)Disease control rate following 1st Re-Induction in this study 6)Duration of response following 1st Re-Induction in this study 7)Time to resp. following 1st Re-Induction in this study 8)OS following 1st Re-Induction in this study 9)Repeat response following 2nd Re-Induction in this study For all patients receiving re-induction in this study, estimate: 10)PFS from 1st Re-Induction in this study For the additional secondary objectives, please see section 2.3 of the protocol.;Primary end point(s): To monitor safety of ipilimumab by evaluating the frequency of adverse events and laboratory abnormalities with corresponding severity.;Timepoint(s) of evaluation of this end point: Throughout the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1) To estimate overall survival from the first dose; 2) To estimate 1 year survival rate from the 1st dose; 3) To monitor Immune Breakthrough Events.;Timepoint(s) of evaluation of this end point: 1) At the end of the study 2) 1 year 3) Throughout the study | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czech Republic, Denmark, Finland, France, Germany, Hungary, Israel, Italy, Norway, Peru, Poland, Russian Federation, South Africa, Spain, Sweden, Ukraine, United Kingdom, United States
Contacts
Public ContactEU Start Up Unit
Bristol-Myers Squibb International Corporation
Outcome results
None listed