Clinical Trials Register

Summary
EudraCT Number:	2009-016631-35
Sponsor's Protocol Code Number:	NCT-2009-11-02-53
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2010-05-31
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2009-016631-35

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Ipilimumab bei Patienten mit fortgeschrittenem Malignem Melanom und vorbestehender spontaner Immunantwort gegen NY-ESO-1,
eine Phase II Studie

A.3.2

Name or abbreviated title of the trial where available

CTLA-4 NY-ESO-1

A.4.1

Sponsor's protocol code number

NCT-2009-11-02-53

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Universitätsklinikum Heidelberg
B.1.3.4	Country	Germany
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Bristol-Myers Squibb
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	NCT Heidelberg
B.5.2	Functional name of contact point	Principal Investigator
B.5.3	Address:
B.5.3.1	Street Address	Im Neuenheimer Feld 460
B.5.3.2	Town/ city	Heidelberg
B.5.3.3	Post code	69120
B.5.3.4	Country	Germany
B.5.4	Telephone number	++496221567229
B.5.5	Fax number	++496221567225
B.5.6	E-mail	Dirk.Jaeger@med.uni-heidelberg.de

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Yervoy
D.2.1.1.2	Name of the Marketing Authorisation holder	Bristol-Myers Squibb Pharma EEIG
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	BMS-734016/MDX-010/Ipilimumab
D.3.2	Product code	BMS-734016
D.3.4	Pharmaceutical form	Concentrate for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	477202-00-9
D.3.9.2	Current sponsor code	BMS-734016
D.3.9.3	Other descriptive name	IPILIMUMAB
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	Yes
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	recombinant, human monoclonal antibody produced in genetically engineered CHO cells

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

patients with advanced melanoma and spontaneous preexisting immune response to NY-ESO-1.

E.1.1.1

Medical condition in easily understood language

Patienten mit fortgeschrittenem Malignem Melanom und
vorbestehender spontaner Immunantwort gegen NY-ESO-1,

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	HLT
E.1.2	Classification code	10027156
E.1.2	Term	Skin melanomas (excl ocular)
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

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.

E.2.2

Secondary objectives of the trial

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)

E.2.3

Trial contains a sub-study

E.3

Principal 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 for up to 26 weeks after the last dose of investigational product, if their sexual partners are WOCBP.

E.4

Principal 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.

E.5 End points

E.5.1

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.

E.5.1.1

Timepoint(s) of evaluation of this end point

at week 12, 24, 36, 48

E.5.2

Secondary end point(s)

-Disease Control Rate (CR, PR, SD) according to RESIST Criteria
-Progression free survival (PFS)
-Overall survival (OS)

E.5.2.1

Timepoint(s) of evaluation of this end point

OS: after 12 months

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Information not present in EudraCT

E.8.2.2

Placebo

Information not present in EudraCT

E.8.2.3

Other

Information not present in EudraCT

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The estimated duration of the study is 24 months including patient enrollment.
Last patient out: June 2014
Trial report completed: June 2015

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.3

Elderly (>=65 years)

Yes

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Patients with sustained clinical benefit and whithout any irAEs requiring discontinuation of therapy might switch to commercially available drug according to the discretion of the treating physician.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2010-08-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-09-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-06-03

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials