Phase II Trial of Ipilimumab in Patients with advanced melanoma and spontaneous preexisting immune response to NY-ESO-1 - CTLA-4 NY-ESO-1

Phase 1

• Conditions: patients with advanced melanoma and spontaneous preexisting immune response to NY-ESO-1.; MedDRA version: 17.0Level: HLTClassification code 10027156Term: Skin melanomas (excl ocular)System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2009-016631-35-DE
• Lead Sponsor: niversitätsklinikum Heidelberg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2010-05-31
• Last Update Posted: 24 August 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 25

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

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) < 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.

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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified