Clinical trial: NCT02203604
Section: Confidentiality
Subsections: Per\Iission (Authorizntion) To I.Ise Or Share Health Ii{F'Ormation Tiiat Idei(Tities Yoti Tor A Research Stttdy|W-Haf Informttion About Me Will Be Userl?|Refluest To Store L,Eftover Tissue* Samples For Futurr Resesrch Llse

hifcrnnation atrout you and 1,our health is personal and prirrnte. so this infonnation generally camot be used in research rvithout yoru writterr pennission. The next few paragqraphs tell you about horv researchels rvant to use and share yorr health iulbnrration in this research snrdy. Yotr Protocol: A Phase II Single Amr Snrcly of IL-2 and Ipilunrinrab in Patientr r,,'ilh uruesecrable Itr aud I\r \.Ielanorna Principal Inlestigator irfonuatiott will orrly be used as described here or as allorved or required by law. Ask questions if you do not urtderstand any parl of the research or the use of your health iufonuatiorr. If you sipur this consettf fonn, .vou asee t0 let the researchers use your inibrmation in the research and share it rvith others as described trelorv,
\ilhat is the purpose of the research antl how will my information be used?  
You are being invited to take part in tlis research snrdy which is described at the begiruring of this tbrur. The purpose of collectirrg zurd tmirrg your health information for this study is to lrelp researchers an$wer the questions that are beirrg asked iu the research.

r All iuforrnatron in yotu ureclical rccorel o Hospital discharge suururanes o Radiology records or images (I\'IRI. CT. PET scans)
r Medical historv or treatment r Meclicatious o Consultations r Laboratoryrdiapurostic tests or iuraEng I EKG aud./or EEG reports r Psychological testing, surueys or questiouuaires r Pathology- reports^ specirnen(s) or slide(s)
r Operafive reports (about a suryery)
r Emergeucy Medicine reporls use, share or receive ury information?  
  
'ch team nlay tue or share your infonnation collected or created lbr this study lvith the people alrd institutions :
r Represerttatives of tlre National Cancer lnstitrrte {NCI). Food and Dnrg Adurinistration
(FDA), artd other U.S. and international goveurmental regulatory agencies involved iu overseeing research fltose persons or orgarrizatious thal receive yoru' intt'rnrration nury not be requiletl try F'ederal privacy lalvs to protect it and may share votu'infbnnation with others without your penuission, if pennittecl by the larvs goveming thern.  
Protocol: A Phase II Single turtr Snrcll' of IL-? and Ipihunimab in Patients '"rith uruesectable Stnge ltr and I\.r \,Ielanorna PrincipaI hn estigator:
f be nble to reliew my re$eflrch recorcl while the re$eflrch is ongoing?  
No. We are r)ot able tr: share infbnrlation in the research records with yr:u uotil the study is over.  
To ask lbr this infonuatiorl. please contact the Principal Lrvestigator. lhe persorr in chalge of this research stucly.  
Do I have to give my permi*sion?  
No. You do not have to penuit use of your inlorruation. But. if you do not prive penrrission. you caturot take part irr this resenrch study. (Saying ilo does not stop you troul gettiug uredical care or other benefits you are eligible tbr outsicle of this study.)
If I sa1'yes now, can I change nrv mind nntl take ilwr-v my permission later?  
Yes. You ma,*- chauge )rour mind and uot allow the contiuued tue of you inforuation (and to stop takirrg paft in the snrdy) at any tinre. If yotr take away per:nission, your infonnatiou will no longer be used or sharcd in the study. but r,ve r,vill not be able to take back information that has already been trsed or shared rvith others. If you say' yes uorv but chauge -vour urind later for rme of your iufr:nrratiou il the research. ,vou umst ivrite lo the resealcher aucl tell him or her of ,voru decisiou:
How long rvill my permission last?  
Tltere is no set date wheu your penuissiorr will end. Yotu health irfonrratiort uraybe studied for many years.  
\Vhere car you get more information?  
You rnay call the National Czurcer Institute's Calcer Lfonnation Senice at: Voice: l -800-4-C:ANCER ( l -800 -422-6231)
You may also visit the NCI Web site at lrtllr;jcatrr:*J,sil],j For NCI's clinical trials inforrnation, go to: htft::,ile trrc*r .fl*r"clinicrllritlr' For NCI's general irrfbnuatiorr about cancer. go to hfl$:,'jltucer.Sovicrur:elurfqrr If you do rtt"rt have access to a persoual courpuler. you llmy access these websites and other infbnuatiEru at a courputer m the R e aucl Learniug Ceuter on the secoucl floor of thel
-
If you agree a biopsl, u'ill be used tr: determiue horv the irrumme systeru is respi:nding to the treaturent. The tlrst saurple of your nunor can be tr-om a previous biopsy that is available, rvill be obtained or, ilthere is a mela:rorrra that can be easily reuroved try a biopsy irr the office a saurple rvill be taken. 'I'lte secoucl silurple u,ill be takeu al fhe begiruring ollhe uraiutenance phase
(arotutd u,eek ft). The thirt"l saurpie rvill tre taken arorurd the tiure you coure otTtreatrr. ent.  
Risks Associatecl rvith Optional Biopsies Prolocol: A Phase II Single Anu Snrcl,v of IL-2 and Ipiltunimab iu patientr with ruuesecrable Stage Itr and I\i \,{elanorna Principal Ilr;estigator:
PLEASE INITLdL ONE OF THE FOLLOWING:
You r[ay choose not to have this procedrue if you do not want to. You uray still lre eurolled in this study if you say no.  
I agree to have a biopsy of uty ttunol, if ury doctor feels it is appropriate tbr me.  
I do not agrree to har.,e a bropsy of ury truuor.  
Text continued on next pnge  
o ltlinor bleediug at the biopsy site r Teudenress nt the triopst site
Protocol: A Phase II Single furtr Snrdy of IL-2 and Ipihrtdnrab in Patients ruirh urueseciable Stage III
and I\r \.Ielanorn"l PrincipaI Investigator:

*We use the terru'"tissue" lo refer to specirueus such as blood. urine, existillg already taket tumor tissue front a previous stugeli bet'ore entering this stucly. or tissue taken fiuur a srrgery as palt ofthis research stucly.  
We ask your peuuissiou l: store leil r:r,er tissue sarrrples collectecl li"onr you during a previorrs surgery attdlor dunng this study l'or frrhrre research. Followilg are details about our request. Please knorv tlmt yclu uray still participate iu the nraiu study even if you say lro to this request to store trssue for frrture research.  
Ilorr rntl ryhere rrill vour leftover tissue br stored nnrl Yotu'lettorrer tissue sarnples rl'ill be stored in the rvhich rs oq,rred aucl whom?  
  
1'he purpore of flte rt'positorl, is lo stole let{over tissue saurples to be usetl for trrtule research lo be cottductecltl-vtlrePrirrcipalhtr,estigattrrarrt1thet.esearclt'.otTo,E.thu goal r:f the researclt is to better uuclerstaud and clevelop better rneans Io prevellf. diagnose auci treat disease.  
All of the subjects iu this stucly rvill tre asked to allow lefiover tissue lo be stoled aud used lbr furure use in the repositr:ry. The mole sarrrples aud health infcrruration available in storage. the morc useful the repository rvill be tbr rnedical research.
Clinical trial: NCT02203604
Section: Duration of Study Involvement
Subsections: Lonp Term Surryival Follow- I-Lrr|To Bf Co\Ipleted \I]Tiiing 2 Wieks Ot'Sttdy Drl:G Ad}Iinistr,Ition To Be Coiipleted Within 72 Hoi"'Rs Of Studv Drus Adiiinistrttion

Affer your end-of-treahnent r.isit. you rvill be contacted everl six lnorlths for up to 36 urouths total (3 years) fi'om ;*oru' first close. During this linre you ilra-"* also tre asked to retunr to the clirric to have bir:psies done of yoru'lesion(s).  
If you leave the stucly lbr any reason. you will be contacted by phoue every six urontlx to see how yon are doing, Protocol: A Plnse II Single Anrr Snrcly of IL-f and lpilrmriural-r in Patientr lrith uruesectable Stage III
and IV llelanonra Ptincipal Investigntor:  
| Table 1:                                    | Long Term Follow 1lo   |                      |             |        |     |    |    |                |    |     |    |    |
|---------------------------------------------|------------------------|----------------------|-------------|--------|-----|----|----|----------------|----|-----|----|----|
| Induction                                   |                        |                      |             |        |     |    |    |                |    |     |    |    |
| Procedure                                   | Screening              | Irrductiou           | Maintenance | End of |     |    |    |                |    |     |    |    |
| {ssessrnel                                  | Treallnent             |                      |             |        |     |    |    |                |    |     |    |    |
| t                                           | Tx                     |                      |             |        |     |    |    |                |    |     |    |    |
| Tx Tx                                       | 7                      |                      |             |        |     |    |    |                |    |     |    |    |
| 5                                           | 6                      | FI                   |             |        |     |    |    |                |    |     |    |    |
| F/                                          | YI                     | U                    |             |        |     |    |    |                |    |     |    |    |
| U? U3                                       | 4                      | LTFU evety 6 months. |             |        |     |    |    |                |    |     |    |    |
| Tx 8 Fi u-!                                 |                        |                      |             |        |     |    |    |                |    |     |    |    |
| h'e                                             |                        |                      |             |        |     |    |    |                |    |     |    |    |
| fteatmeut Tx Tx                             | Tx                     | FruI                 |             |        |     |    |    |                |    |     |    |    |
| I                                           | 2                      | jt                   | 4           | Fru 6  |     |    |    |                |    |     |    |    |
| _1                                          | I                      | 4                    | 7           | 10     | l2  | 34 | 36 | 48             | 60 | 104 |    |    |
| Montlx                                      | I                      | :1                   | 6           | 9      | 12  | 34 | 36 | Every 6 months |    |     |    |    |
| Medical History                             | x                      | x                    | X           | x      | x x | x  |    |                |    |     |    |    |
| Phvsical Exauiuatiou                        | x                      | x                    | x           | x x    | x   | x  |    |                |    |     |    |    |
| Vital Signs (includirrg reisht and weiehl)  | x                      | x                    | x           | x      | X   | X  | x  | x              | x  | x   | X  | x  |
| Adverse Events AssessmeutlCon Meds          | X                      | X x                  | x           | x      | X   | x  | x  | x              |    |     |    |    |
| Blood Tesls                                 | x                      | x X                  | x           | X      | x   | X  | X  | x              |    |     |    |    |
| Jrfuralysis                                 | x                      | x                    | x           |        |     |    |    |                |    |     |    |    |
| lepmncy Test                                | x                      | x                    | x x         | x      | x   | x  | X  |                |    |     |    |    |
| JKG                                         | x                      | X                    | T           |        |     |    |    |                |    |     |    |    |
| ,lardiac Stress "l'est                      | x                      |                      |             |        |     |    |    |                |    |     |    |    |
| \rlmonary Furlction Test                    | x                      |                      |             |        |     |    |    |                |    |     |    |    |
| CT or MRI                                   | x                      | x                    | x           | x x X  | x   |    |    |                |    |     |    |    |
| lesezuch Blood Tests                        | X                      | X                    | x           | x      | x   | x  | x  | X              |    |     |    |    |
| fissue                                      | x                      | x                    | X           |        |     |    |    |                |    |     |    |    |
| :ollection(ootiorral ) itudy Treatrueut L-2 | {                      |                      |             |        |     |    |    |                |    |     |    |    |
| pilinxunab                                  | K                      | (                    | t           | K      | t   | f  | x  | x              |    |     |    |    |  
Can y'ou stop being in the stutlv?  
Yes. You can decide to stop at arlv tirne^ Iell the doctor if ,'--ou are thiuking about stoppirtg or decide to stop. He or she r.vill tell you horv to stop saf'ely.  
It is irnportant to tell the doctor if you are thinking about stopping so any risks frorn tlre study tlnrgs Prolocolr A Phase II Single Ann Snrdy of IL-2 and Ipihurrirnab irr Patienm with ruresectable III
ald I\r \.Ielanorna Principa I Inlestieator:
cau be evaluated by your doctor. Auother reason to tell you"doctor that you are thinkiug about stopping is to discuss q,hat tbllow-up care ancl testing could be mr:st helptirl for you.  
The doctor may stop you fi'oru taking par"t in thjs shrdy at any time if he/slre believes it is in your best interest. if you do not follow the shrdy nrles. or if the study is stopped.  
Whst nre the risks antVor tliscomforts you might experience if you take part in this study?  
You may have side efftcts wlile on the study. Everyone taking part in the stucly will be lvatched carefully for any side effects. However. doctors dou't know all the side eftects that rnay happerr. Side etTects uray tre mild or very serious. Your health care teaur rnay give ynu uredicines to help lesseu side etfects. Many side effecls go away soou after you sfop taking the shrdy drugs. h sorne cases.  
side eflbcts can be serious. long lastiug, or rnay rever go arvay. Therc is also the risk of death. You should talk to yotu doctor about auy side ett'ects that you have while taking parl in the study.

2{.0 Pregnanc-v- Test (Senuu)- if applicable  
  
Note: Dav I is 0K
tt Prolocol: A Plra.re II Strgle .furu Shrdy of IL-l nnd Ipilinrunrab in Parienrs rvith LLuesee-table Staee III arrd Stage i\' Ilelanonn If oFF sruDY FoRM
Protocol Number: A Phase II Single Arm Studl' of High-Dose IL2 anel Ipilimumnb in Prrtients n'ith ['nresectable rtage Ill and Stage I\'\Ielanomrr. I I
lnvesti gator ldentification lnstitution and affiliate name lnvestigators name Patient ldentification Patient's initials (Last, First)
Registration number Date Subject is Off Study (mm/ddlyyyy)
best response achieved; date  
  
Reason Subject is Off Study: tt  
  
progressive disease; date toxicity; describe lost to follow-up physician preference patient withdrawal; reason patient never received tx; reason other: describe lnvestigator Name (print)  
  
Signature of lnvestigator Name Date Protocol: A Pluse II Sirtgle Ann Shrd,v of IL-l and lpilinrunrab in Parienrs tvirh Llu'esectnble Srage  
  
III and I\i \{elatronra Prilcipal hr.-ertigaror, f Protocol Versron Date: 19 Julr'2015 \:ersion: -j.0  
  
  
Protocol: A Plrase II Siugle Anrr Shrdl' of Higlr-Dose IL-l ancl Ipilintuuab in Patierus rvith thuesectatrle Stage  
III and Staee I\' \lelanourl  
Principal Iilestigaror: f  
ECOG  
| Principal Iilestigaror: f ECOG nce status table: Description                                                                                               | Grade   |
|------------------------------------------------------------------------------------------------------------------------------------------------------------|---------|
| Fullv active, able to carrv on allpre-disease pedormance without restriction                                                                               | 0       |
| Restricted in physically strenuous activity, but ambulatory and able to carry out                                                                          | 1       |
| work of a light or sedentary nature, i.e. light housework, office work. Ambulatory and capable of self-care , but unable to earry out any work activities. | 2       |
| Up and about more then 50o/o of wakinq hours. Capable of only limited self- care, confined to bed or chair more than 50o/o of                              | 3       |
| waking hours Completely disabled. Cannot carry on any self-care. Totally confined to bed or                                                                | 4       |
| chair Dead                                                                                                                                                 | 5       |  
| KPS   | ECOG   |
|-------|--------|
| 100   | 0      |
| 90    | 1      |
| 80    | 1      |
| 7A    | 2      |
| 60    | 2      |
| 50    | ?      |
| 40    | 3      |
| 30    | 4      |
| 20    | 4      |
| 10    | 4      |
| 0     | q      |
Clinical trial: NCT02203604
Section: Possible Risks, Discomforts, and Inconveniences
Subsections: Ltion Immune-Bssed Risks Associtted With Lpilimumab:|Immune-Basetl Events Con"Sidered To Be Relsted To Ipilimum*B|Blood Drau' Risks|Risks Relatetl To Imaging Procedures|Are There Any Anticipatetl Pregnancy Risks? Women

While receiving lrcalureut rvith ipilimmnab. you uray be at risk of side effects that occrr durirrg or shorlly after the irrtirsion (within 24 horus). or later afler the inlirsiorr lras finishecl. hr isolated cases, sorne ipilirmunab-related side effects may occur many montln after the last dose of ipiliurumab.

Tltere are side ellbcts that rnay also occur that are called irumrure-based events (where your inuuuue systerD at{acks yc}ur nolnlal cells)^ The uraiority of the sicle effects seeu $o far have uot treeu $eriorm.  
horvever alutost 50q,6 of all participants receiving ipilitruurab have experienced an imruune-based event. Serious eveuts are side efTects rvhich are fatal or life tlueaterring; require you to be hospitalized: rlray peiluarrently disable you or urake you rveak and rurable to fiurctiot at your cuneut level: or ruay jeopartlize you or rcquile srrgery or intervenlion by your doctor.  
Tltese iuunune-trased side ellbcts have uslrally treeu coutrolled by stoppiug ipilimtunab treaturent and if needed, with rnedications. inchrdiug steroids (nredications that arc rxed to decrease inflanurration).  
If you develop an irrunune-tiased event. the syrnptorus uray take seveml months to improve.  
Inuuure-basecl sicle effects obserued in previous Ipilirnunralr research studies irrclude:
o Esophagusi Stouracl/lntestine: Ttre urost couulrclu stornach, irrtestirml event is dianhea, r.vhich has occurred iu aborrt I09 o of-participants takiug iprlimumab. Dialhea due to ipilinnunab ranges h'our rnild to very severe rvith bleecliug and rnay be lit'e threateniug. Sonre cases of diarrhea lmle started out as rnild and then beconle severe. About l9'b of participants have liad diarhea or storuacluirrtestirral cr:rnplicatrons that required sugrcal remol,al of parl of their intestine or resulted in death. All other cases of diarrhea have been successfirlly treated by either stopping ipilirmunab ancllor treatulert with anti-diantea rnediciue or with steroicls. About 109'n of parlicipants treated r.vith ipilirurunab have alsr: developed abdourirral paiu either alone or iu cornt;irratiou with diarrhea. Rarely. constipation uray be associated rvith ipilirnrunali.  
You shoulcl tell your doctor if you develop afly diarrhea. constipatiou. auy charge in vour bowel
[roverller)ls. have blood in your stool. or have abdorniual pain. Yoru doctr:r nray lvant to perfotut tests tr: befier turderstand rvhy you have these syurytorns. These tests will allow your doctor to look at 1.oru nrtestine tbr damage. It rnay also help detennine the type of treatureut you uright need, which rnav urclude the rue of steroids. You urayhave to so into the hospital for doctors to investigate and treat the diarrhea or other storuachlintestiral spnpfolns.  
Also. there cal tre hrflanuua(ir:rr of the esophagus (grrllet or the tube that goes tlom mouth to stomach tlrrough which tood passes) that can make sr,valiowiug ditticult r:r painftll.  
In addition. if-vou tr:ok IL-2 (auother drxs sonretiures used tbr ruelanorna) before ipilinrurnab, or take IL-2 alier. you urav iucrease yotu chance of borvel perforation cr:rurpared to taking IL-2 alone. A borvelperfbration lneans that yoru borvel, surall or large. has developed a hole which allorvs the conteuts of voru intestine to lenk into the abdomeu. This is considered a medical prorocolr A Phase II Silgle Anu Snrily of IL-2 and Ipilrrmimab in Patient$ nith tttuesectable Staee III
and I\i \.Ielanorna Priuc ipa I Inr,esli€rator:
emergency as it causes a severe iufbcticrrr which cau result in death. It has also been reported that patielts with bowel metastasis of urelanorna (melanorna carlLrer which has spread to the bolvel)
ulight be nt higher risk of bowel pertbratiou (tear), rvhich could alsr: result in death. If you krrow you have tiiverticulurn (prohusion of sotl tissue tlrrough the colonic rvall) antUor diverticulitis
(irrf)anunatiou in the diverficuluru). 1'ou lleed to tell your doctor and yotu doctor will evaluate rvhether it is apprr:priate to treat yott rvith ipilirnurrrab.  
r Rash: Rash is a conunon inunuue-based event in paflicipants treatetl with ipilirnturtab. Rash has occumecl iu about ?09'o of participantsl most cases ltave beeu mild arrd less than l9'o of cases have lreeu sedous. Soure participants have had itching Rloue or together with the t'ash. There can also be hrtlanurraliort ,:r tlatttage tcr tlte tisstre wltere a clurg was ir{ected r The eye: In rare cases. atluunistration of ipilirnumab has beelt associated with iuflamtuatiott i1the variorn pafis of the ele or rvith pigrnent (color) changes irr the retina. There have been uo lurolvu cases of pet'lllanent eye daurage but tltese couditions cculd potenlially intertere with y'otrr eyesip{rt or ever} cause bliuduess if urrtreated. If these cortditions develop, they rnay require treatrnent to recluce inflanuratiou. hr rare cases. double visiott occrured as a result of urttscle wealaress. You sh,rulct iuuuediatel.v tell your doctor if you think tliere is a change ur yoru eyesight. if you develop clouble visiou. or if you develop eye pain while you arc ou this shrdy.  
r Pancreas. Lrtlaluuatiolr of the pancrcas is called partcrcatitis. Pancreatitis carl occtu suclderrly
(called "acute") t'rr it can occur slor.l'l,v over tinre (callecl "cluottic"). Syllptoms r:f pancreatitis trsually incllcle abclouiual pairr. uausea. vourittug, and f'ever. Your pancreas is responsilrle tbr prodtrcing digestrve el).z).rnes rvhich hetp the body digest tbod as rvell as producing irxuliu which irelps rnaiutaiu 1'our bloocl sugar levels. I\'lild acute patlcl^eatitis usually tloesn'l perrttartently affect cligestion or bloori sugar levels. although a sirtgle severe attack can tlatnage yoru paocreas and trigger chronic pancrea(itis. r.l.hich clestroys the cells tltat protluce botlt eruytres and insulin.  
Ougoiug clamage to enzltne-producing tissue in chrottic paltcreatitis leads to poor absorption
(gralabsorpticur) of uutrients. especially thts. to rveiglrt loss. atxl to clily. utalodorous stools.  
Damage to or clesrruction of insulirt proclucing cells means bloorl sugar isn't rttetabolized properl,v. often leading to cliabetes.  
o Egdocriue glands: Rarely (approxiurately 2%). parlicipants have developecl l:roblerns witlt pafiicular glarrds (a glant{ is a group of cells ol all orgarl that sect'etes a horrnotral sttbstauce) sttclt as the pinritary glancl. the thltoid, or the adrenal gland. SlTttptours that rtlay be associated with prr:blerns of the pinritar-v or adrenal glancls inclutle tatigue. contitstott. weight loss. irmbility to perfonn sexua ll;r (irrrpoteuce). and headache.  
o Liver: Approxirnately 49,o of participauts have developed serious problerrrs with tlte liver as a resglt of ipiliuurnab treatment. Intlarruuation of the liver clue to ipiliurumatr can range fiom nrild to severe- ancl iu very few,cases, it can be life tlueatening. Horvever. utost severe cases lnve lreetr sqccessfirlly treated by stopping ipilirrnunati treatulent and by adrrrinistering anti-intlamrnatory Protocol: A Plmse II Single Anu Snrcly of IL-2 and Ipilrrmimab iu Patients u,ith uruesectable Stage Itr and I\,' l{elanorua PrincipaI Intestigator:
medicatiolls such as steroids, You should coutflct you'doctor if you experience synptoms that nmy be associated r'vith problerns of tlle liver that irrclude thtigue, lr'eakness, vonfting. rausea, anrl atrrtoruinal pain. More frequent blood clmlvs and a lirrel biopsy may be rcqrircd if you develop seriorx liver abnonnalities.  
o Other organs: Rarely, participarrts imve developed protrlerus with the liver. kidney
(proteimuia which is extra protein in urirre). heart. rnrmcles, blood r.essels. and lurg while taking ipilinruurab. Acute tlilure resulturg in cleatli has occured in less than lo;ir of participants.  
Slurptours that ruay be assr:ciated rvith problerns of the liver iuclude fatipnre, weakness.  
vorniting. ralrsea. and abdourinal pain. A liver biopsy uray be required if you develop serious liver abnortralities. "Ioo ruuch bile irr the bloocl causing a yellow color to the skin. glun$. eye.  
and other tissues fiaundice) cr:uld occur.  
o Ir.{euingitis (intlarrurratiou of the ureurbmne sruroundiug the spinal cord and brain) has developed in less than lo,o of parlicipants treated with ipilirnrunab. This can causje headache.  
rlausea and vorrritiug. stiff ueck. and sensitivity of yq111eyes to light.  
r In very mle cases, iuuuute-related urotor lleruopilthy (intlarrunation ofthe nerves thnt control muscles) such as Guillain-Barre Syrdrorne may occur. which could be life-threatening if not treated appropriately. You sltoulcl tell yoru doctor if you experience r.vealuress of yoru lirntis with or rvithout numbness or tingling. In adclitiou. there can be pn:gressive lveakness caused by the body's inumure systern attacking the skeletal rnuscles (lnyasthenia gmvis)
o Neplritis (inflarrunation of the kidneys) has developed iu less than l% of parlicipauts tleated with ipilirnunab" The cases ol'ureningitis and nephriti,s resolved wilh treatmeut.  
r A conclitiou where the skin loses pigrueut aud tuurs white (vitiligo), has occured iu less than 596 of participants. This corrdition is likely to be irreversible and pernaneut. A condition in which blistering aud peeling of the top layer of the skin occurs ald rcseurbles a severe lrru:r have beeu rarely reportecl. This is called toxic epidennal uecrolysis. It can be very severe and nray result irr death.  
r You slumld tell y'our doctor iuuuediately if you thirrli you are developury aoy uursual side effects even if they lveren't listed here or any of the side effects or slrnptoms listed.  
o Over-the-corurter (OTC) tlnrgs may cause major side etl'ects. Acetoruirrophen and NSAIDS
tbund in rnost coullnoll OTC products for cold. headaches. uruscle aches. and fever are safe and effective when used corectly. but too rnuch can damagre the liver'. Be cautious rvhen using OTC
prodtrcts. If you choose to take an OTC product. infonn tle nursing staffor you doctor alxxt tlte dmg.  
Lr addition. inuurure-based reactious of an-v other organs, such as the joints or heart, could also occul'. This could cause paiu and sw'elling. Joint pain has been repofied try less than l% of Prctocol; A Phase II Sirrgle fuiu Snrll'of IL-? and Ipilutrimab iu Patients u'ith utuesectable Stase III
and IV \.'Ielanorna Rincipal Inr"estigaror participauts receiving ipilinlulrab. hrflarnmation of the ltearl or carditis rnay occur in all aspects of the healt aud symptoms rnay iuclude shortness of breath. fatigue. antl chest pain. Treatment of the inllauurmtion depends or the aspect of the hear"t rvhich is atl'ectecl. It rnay lead to decreased fi.urctioniug of tlie heart.

You uray experience pairr or discornt'ort. bnrisiug and/or bleediug at the site the rteedle enters the body. ard in rare cases. lhiutirrg. liglrt-heacledrtess or infection.  
Risks Relatetl To Imaging Test Radiation Racliologic testing, such as C T scaus. tvill lre used to assess the treatutent of your disease at variotts tirnes during therapy, The total radiatiorr exposure ti'om these tests is cortsidered srnall and is not likely to a1li:ct you in a negative rvay. but cau adcl trp cver titte.

The contrast solution (a dye that is intected to get a clearcr pictrue) that rnay be given for a CT sczur or MRI rrray cause an allergic reaction (rare). CT Corrtrast dye coutains iotline aud if you are allergic to iodine or shelltish you should notiSr your tloctor and racliology lab prior to haviug the C I scan.  
The C'T coutrast sr:lutiou cau carrse kidney darrmge, especially if you are tliabetic. dehydrated. or elderly. When the co[trast uteclirurr is iniectecl durirrg the C'T scan, you may experience llattsea.  
tlushirrg. wanuth. or a salty taste.  
Prolocol: A Phase II sirrgle Ann snrcly of IL-2 zurcl Ipilrrnrirnab il patients with ruuesecrable Stage Itr and IV Melanonra PrincipnI Inr,estigaror:
h MRI shrdies. yotl will be required to lie in a uaffow tube, r,vhich illaynnle you fbelulcou11o$able or claustt'ophobic. The MRI rnakes loucl liangiug noises. You rvill be given earplugs if yotr rvqulcl Iike them, If f i:ru arc tbelttlg tulcorfofiable. thii stutly cnt be stopped at nny tiure at yoru request.  
You should not have an lt'{RI if you have a paceruaker. or nretal piate i1youl.body. In unco'uuon cases Yoll uray experielrce tel]]Poratl or evet) pemlarler)t kidney tiamage due to the contrast urediun

If you ale preglflnt or breasffeeding. you cannot take parl in this study. A pregnancy test is recluired and will be given belbre you slart the treatnreut and urainteriance phase. \Jo1a1e responsible tbr usirrg au etl'ective birth contlol ruethocl such as birth coltrgi pills, barier grethocl
(such as condours or diaplrragnx). intrauterine clevice (ruD). homrone implants or surgical sterility while .vou are takirtg part in this stucly. Once you have courpletecl ireahnelt, you rnay discontirtue birth coutrol after I rnonth of corrrpleting treatment. If you become pregna,t. you trust notity the shrdy docfor iuunediately.
Clinical trial: NCT02203604
Section: Procedures
Subsections: Screenins|Treatment Induction Phlse (\\'Eeks L-12)|Maintenance Phase|How Will Samples Be Collected?

The stlcly doctor and possibly other stucly 51sf6 rvill explain the shrdy to 1.ou arrtl answer any qttestions )rou ulay have. If yotr decide tlnt you nmy tvant to participate irr the study. you rvill be asked to read and sign this Clornent t'orur. The screening visit with the stucly tloctor will take approximatel-v I hour.  
You will ueed to have the followiug exaflrs. terits or procedures to fincl out if you carr be in the shrdy.  
These exaflls. tests. or procedures are parl ofregular callcer care and uray be done even ifyou clo not join the study. If you have had soure of theur recently, the1.'uray not ueetl to lre repeatecl. This will tre rup to yolrr doctor.  
a t  
A metlical history (questions about vrmr health. cufl'ent ruedicatious. aucl auy allergies).  
A physical exrnl. The research cloctr:r or another research healthcare professional will complete a physical assessrneut, irrclucling blood presstue. pulse, rate of breathiug.  
telrlperatlue. alcl heiglrt and weight.  
An sssessmenl of vour tumor by C'I (Courputerized T'ouroElraphy. also klorvn as a CA'f scart. A CT scan is a tetYtletailedx-rayes,alrr.) Scans c,f yourchest, at:t{orrren. andpelvis must tre pedbrurecl withil 28 days of starting shrdy tl'eatureut, and an ClT(Conrputerizecl
Prolocol: A Phase II Single turu Snrcl.v of IL-3 ancl lpihrnrimab in Patientq rrith ruuesectable Stage III
aud IV \.Ielanornl PrincipaI Inr.estigator:
TomoE'aphy) or tr'{RI (ll'lagnetic Resonance hnaging) of your braiu rnusl be perfonrrecl rvithin 28 days of starlirrg study treatfilent.  
r Blootl tests. Blood (about 2 tatrlespoons). will lre taken fi'oui a vein in your ann to cheek blood cell coturts. how well .volr orgars arc fi.urctioniug. and to test tbr any infections.  
Blootl test for pregn&nc\'. if you are a wolrlan of child-bearing poteutial. (This test must be collected rvithin -1 days ol'stucly assi$uueui.) Approxiruately one teaspoou of blood or less rvill be drarvD tbr this test.  
. A sxmple of your turnor (optional) to detennine how tlie iuumure systenr is responding to tlte treattnent a sarnple of 1'our tuuroL frour a previous biopsy that is availatrle will be obtained or. if there is a urelanoo)a rhat carr be easily lernoved by a biopsy in the office a sanrple rvill be kken. You mav choose not to have this proceelure if you rlo not want to. You mrt, still be enrolled in this sturty if you ssy no.  
If these lests show that you are eligil:le to parricipate in the research study. you will begin the snrdy h'eatntent. If yorr do not uteet the eligibility criteria. you ivill uot be able to participate ur this researclr shrdy.

If you take part in tltis research stucl.v. you rvill receir,'e ipilirnrunab liy arr intirsion ilto a vein (LV.) or cetttral line (port-a-cath) at weeks 1.4, 7. and l0 (cycles l. ?.3. and 4. where each cycle equals ?1 days) tbr a total of tbur intirsions. The intusiou tiure is roughly 90 ruiuutes h length. The infirsion will occtrr at au otttpatient faciliry-. You,lvill have your vital sipurs ureasured prior to the infirsion, and evety 30 utitttttes durirtg the infusion procesis. (hre hour atter the iulirsiorr has stopped. yoru vital signs will be rtteasuled one rnore tirue. Thus. the w"ltole inftrsion process takes about ? lrl to 3 hours.  
hr addition. .votr rvrll receive high-close IL-2 according to the rnrml standard at ycnr hospital. You tt:ayneed lo underso additiorral testing prior to IL-2 therapy. such as taking a stress test ofyour heart ot'puhuouaty tttuclion sturltes to detenuine if your hearl and lungs are able to tolerate IL-2. The II--2 will be given atier the second dose (r.veek 4) and thild dose (week 7) of Ipihrrnirrrab orrly. IL-2 is given iIr the hospital and lvill reqtfre you to be adnrittecl to the hospital tbr treatruent inunediately atler the Ipilturrirnab on rveek 4 and week 7 .IL-2 rs generally giverr tluotrg{r a celltral irfravenous liue evety 8 ltotus ttp to a total of l4 doses. You rvill be monilored tbr vital sipnrs and trlood work basect on yorlr doctor's recortuttertdatious" I\.'lost patients g,ill be irr the hospital for aboul 5 clal,s at a time.  
r Ph"r'sic:rl Extms: During all treatrneut cycles. you will have a physical exanr. inchrding measurittSl ynur rveip&t. You will be asketl questiolls abor( your general health and specific qtrestions alrotrt any problerns that you might lre having and any rnedicatious you may be taking.  
Please tell your doctor ab,rut any rneclical treatlnents that you r.vill have to get dulurg tlie stucly
(such as elective strrgerv).  
Protocol: A Phase II Single Anu Strrdy of IL-? and Ipihurrirnab iu Patients r.vilh ruuesectable Stage III
and Staee IV \,Ielanonu PrincipaI inr:estigator:
Blootl Tests. Everv 3 r.veeks (every cycle) )'ou wlll uldergo blood tests to closely follow you while you are receivilrs the strrd.v dnrg. These tests will check blood cell coturts aud horv ivell your olgam ale tiurctiorring. Tliese tests ivill be done mole oflen than if you were not on this study.. On certain visits an atldrtioual arnorurt of bLrod r.vill be takeu tor snrdies of your T cells fo see horv the trea(ulent has attected them. This rvill be done at screelrirrs arrcl again at rveeks l, .1. l:. ancl24. Approxinrately 4-6 tal:lespoons of blood rvill be needetl at each visit Assessrrent of your trncer: by CT {C'ornputerized Tomognaphy) of your chest, abdomeu. arrd pelvis and a CT (Compnterized Tomop[aphy) or IV{RI(\.{agnretic Resouance Lrragiug) of your brain. These assessurents will be pertbnrred every l2 weeks If yq6 disease is lbrurd lo lre iurproving. vou rvill be asketl to repeat the ('I antl MRI
scans in atrout 4 rveeks.

If yoru disease remaius stable or contiures to iruprove at rveek 24. you uray receive additional doses of ipilirnumab every 3 morrths after the last dose you received at rveek 12. Prior to receiving the doses you rvill be asked to undergo tlie following:  
o Physical Exnm (rveig{rt and vital sigrs) and questions about your cun'errt health, iuclueling arrl,chauses iu your spnptouls ald any uredication$ you are takiug.  
r Routine blood tests ('about .l-6 tablespoons) to check 1CIrtr bk:r>cl cell corurts. how your orgflils are fiurctioning- aud arr.v ellbcts the drug uray have on youl' blood. You will also be asked to take a pre€nancy test if you are a wonrafl of child bearing poteutial. On cefiain v'isits au additioual aurolult of blood will be takeu for sftrdies of yoru T cells io see how the treatment has all'ected thern. This will be clone at screening, betbre treaturent on rveeks l. 4. 7 and 12 aucl at 6 ruonths and I ? mr:nths. Soure of the blood aud seruut collected may be stored tbr firture studies of the iuunune respoltse.
You rvill coutilue to turtlergo nerv CT aud MRI $cans to evaluale the extent of your disease every l2 rveeks after week 34.  
Experieuce with the dnrg ipilimuurab has showu that fbr soure patients. their disease uray get larger before it stabilizes or gets smaller. hr this sinratiou. we rvill contiuue to follow and treat your disease at the discreticur of you and yoru'c{octor.

Only tbe leftover tissue tltat rvas collected druiug a previous surgely ant{ior as a part of this research study ibr firttue research would be stored and used fol firtrue use.  
Psvchological or Social Risks Associated with Loss of Privclcy:
Wltile the databases developed fcu this project lvill be coded to protect )roru persoual infcrr:natir:n. people may develop ways in the tirtue that would allorv sorneone to liuh you medical information back to you. [t is also possible that there could be violatiorx to the security of the co[rputer systeuls.  
Tltere also rnay be ofher privacy rrsks that rve have uot lbreseeu.
Clinical trial: NCT02203604
Section: Purpose of Research
Subsections: Cotsi){T To Take Part I}I A Risearc:H Stt,Dy|What *Re The Benefits Of Participation?

Title of Study:
A Phase II si,gle.furu srudy of High-Dose rl--z aurl Ipiluuriurab in  
  
  
Patients lvirh tuuesectable Stage III antl stage ft'N,Ielanoura Principal Inr.estigator:
Tltis cotsent for:u is part of au iulbnned consent proces.s l'rrr a research stpcly a11d it r,vill provicte ir*buualiort lhat ivill help y'ou to clecicle rvhether 1ou wish to vohurleer tbr ttris r.esear.ch st.tly. It will help you to understarttl rvhat the stucly i.c about ancl u,hat tvill lrappen in the course of the snrAy.  
If lau have questions at auy tinle during the research stucly. yo6 sholld feel fiee to ask theu a*cl should expect to lre giveu answers that -vou corrrpletely uuderitar:cl.  
After all of yotu'questiotts ltave treett ansrvered. if ,vou still rvish tr: take part iu the study. yo* will tre askecl to sign this iufonned consent fomr.  
The snrdy doctor (the priucipal investigator) or zurother.nremtrer of rvill also be asked to sign this irribnrrecr consent forxr. you will consett fcrrru to keep.  
the study team (au irnrestigator)
be given a copy of the signecl You are not giving tlp anY of .loul legal rights bl- vohmteeritg for this research stucly or by- signilg this consent lbmr.

You will not benefit personally fi"our providing tissue sarnples fcrr this tissue bauli because research usually takes a long tirne to produce rneaningful results. However. your participation may help ittvestigtators urtderstand, preveut" or lreat the diseases and corrditiorrs studied in ttre tirttue.  
  
Protocol: A Phase II Single furu Snrdy'of High-Dose IL-2 ancl Ipilrrmimab iu Patierrt; rvith tuuesectable Staee Itr and I\.' \.Ielanonra Pr incipaI Inr;estigator I informrtion fibout you flnd your tissue srlmples be kept llrivnte nnd confidential?  
Inforrtation obtained iloru this research rvith uaterial obtainecl t}orn yoru tissue saurple(s) rvill be kept confidential so that neither the investigfftor rrot the Sponsor can liuk your indivirirml research resulfs lvith yoru' identity.  
Your saurple(s). and uraletrials ilerived ll'orrr vour xaurple(s)^ will be given a code uruuber. aud only irtlonrration related to yolu'age. ses,. race. health condition and r:ther relevaut clirrical infcrrmation collecteti in the uraut stuil,v* u,ill be liuked rvith the sample's code nuurber. Yorr uatne. date of birth.  
address. or otlter persoral identif.viug iufcrr:natiou. r,vill not be hnked with the sample(s) you give.
Clinical trial: NCT02203604
Section: Voluntary Participation
Subsections: \Yho Mav Not Uarticioate'-)|Agreeiient To Particiktte

You umy not be inchrclecl iu this study if:
r You have ocular.or nlucosal nrelanoura Protor:ol: A Plnse II Single Arut Snrcly of IL-2 and Ipihunimab in Patients rrilh turesectable III
and IV tr{elanorna Principal Intestisator:  
o A histor] of prior treatmeul wiltl IL-2 or ipilirmuuab or CTI,A4 iuhibitor or aftonist for uretastatic disease r You have to take corticoster'oids tlu a clrrouic lrasis o You are pre[prant t:rr breastfeecling
The study cloctor arrtUor research teanr will also ask vou other questions about your rnedical history irr order to make sure quali$ to be in this study.  
How long will the sturly take and how many subjects w.ill particip*te?  
Your participation will last approximately one yeal tirr active tleatulent. tu addirion, you will be follorved for up to 3 years lo see lrorl' you are doing a{ier the treatrnerrt.  
You n:ay be reutoved tiorn this study rvithout 1,our consent for any of the followiug reflsons: the snrdy doctor decides that contitttred participation nr the study will be hanrrfill to you. _vou will need a treatnlert not allowed ou the shrdy, your disease becornes cliuically worse. you ale rurable to take rhe treaturenl as indicalecl. or the shrdy is canceled.

l'ead t() you. and you believe that you understartd what You have read this entire tbntt. or it has been has been disctrssed.  
All of your questiorts atrr:trt tltis fontt or this shrdy have been arrswercd.  
I agree to take part in this strrdy.  
Subject Nanre:
Subject Signatru'e: Date.  
roR }()5- 1."\ (;l . 15 II SPE.'I K t ts{-i $l'B,}Ii{ :.I$ :
Signature of Rearler/Translator If the Subject Does \ot Read Inglish ltell:
The person r,vho ltas sipnred above. . does uot read Euglish Qmnrcofilw well. You lrntgnge).a read English rvell and are t'hrent irr lauggage that the subject (hisiher pareut(s)ilegal guardian) uuderstmtils rvell. Yott understarxl the couteut of this consent lbnu and ),ou harre translated ttrr the subiect (hisi'her parent(s),rlegal guardian)
tfie eltire content of this tbmr. To the best of yl:rur ].lowledge. the srtlrject (his/her parent(s)ilegal guarclial) lutlerstands the content of this fcrmr and has had an opportrmity to ask qrtestions regarding t5e copseut fonu autl tfie stuci1,". a1{ tfuese quesfious harre lreetr attswered (his/her parent(s),rlegal gtrardian).  
ReaderiTrauslator Natne :  
| f)ate:                                                              |       |
|---------------------------------------------------------------------|-------|
| Reader/Translator Sipura hrre : Witrress Narne: Witness Signattrre: | Date: |  
Signature of Investig:ttor/Indivitlull Obtaining (ionsent:
hrrrestrgator./Person Otrtairriug C'ottsertt:
Si$rature: Date:
Protocol: A Phase II Single At:rr Shrd-v of Higlr-Dose IL-2 ancl Ipilinrturrab in Patiertts q'ith Llru'erectabie Stage III and Staee I\,' \.Ielanorrra Pri,cipal Iu.".rtigutor, f SUBJECT REGI$TRATION FORM
Protocol Number: QA"1_94_984  
lnvestigator ldentification lnstitution and affiliate name lnvestigator's name Patient ldentification Patient's initials (Last, First)
Registration number Patient demographics  
  
lnformed Consent Subject signed date (mm/ddlyyyy)
Please attach a copy of the signed t*J
consent document to this form.  
Pathology Please attach a copy of the original pathology report to this form PLEASE NOTE THAT SUBJECTS MUST MEET ALL OF THE ELIGIBILIW
REOUIRMENTS LISTED IN SECTION 4.0 OF THE CLINICAL PROTOCOL
lnvestigator phone pr.otocol: A Plrare II Silgle ,turrr Snrc{1,of IL-l and Ipilinruruab in Patieots ltith tkuerectatile Stage III ancl Staee IY N{elanoura Pdncipal Inr"*rtigntor, f Please note that blood and tumor specimens must be submitted as detailed in Section 12 of the clinical protocol and using the SPECIMEN SUBMISSION FORM
located in the Laboratory Manual.  
SUBJECT ELIGIBILITY CHECKLI$T
Protocol Number:  
  
cA184-084  
  
  
Title: A Phase II Single Amr Strrdy of Higtr-Dose IL-? ald lpilirutunab irr Patients with Uuesectable Stage III and Stage I\.'N'{elanoma Protocol Version Dnte: 03 Oct 2014 Protocol Number: CA184-084 lnvestigator ldentifi cation lnstitution and Affiliate name:
lnvestigator's Name:  
| n                                                | r phone                                            |
|--------------------------------------------------|----------------------------------------------------|
| Participant Narue: (Plint First artd Lasl)       | Patient I\\rRS Screenitts, l'{tuuber:              |
| Attending: ( Print First aud Last)               | Consentirtg Prot'essional : (Priut Filst and Last) |
| Registering hrdivrtlual: {Prilt Fu'st ancl Last) | Registeriug Individual Phone Nttmber:              |
| f)ate of Consent:                                |                                                    |  
| Consent Ouestions: 1.0 Is the parlicipartt flueut in English? O*es,No) I{I'es, skp to tlrc Eligibilit.r: Criterirr .sactittrr: if NO, contittue willt C'or t,s en I Ou e.st i ot t 2. 0 2.0 \Vhat is the participaut's prirnary langtrage? 30 Was an lRB-approved trauslated iutbmred coo$ent trsed in the pafl icipant' s or legallv atrthorized rept'esetttative's primar;* langua ge ?fYESi}ro)   |
|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
Pr.otocol: A Phase II Silgle .A,mr Strrdy of IL-3 ancl tpilimuurab in Patienls rvith Lhu'electable Stage III and Staee IV \lelattotua  
| III and Staee IV \lelattotua Principal Iuvestigator: 4.0 Was an lRB-approved short-tbrln given to tlre pafiicipalt or: legall,v autholized reptesentative iu their prirxary language'l (YESil'lO or NA) 5.0 *as the lRB-approved English consetrt ol'stlllunary signecl tr-v the consentittq professiorml'? (Yes NoNA; 6.0 Was au iuterpreter (non-family l)rettlbel'ol caregivel) used for the discussinu'.) ( \'ESrNr: NA)   |
|--------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
The subject must meet the following criteria to be eligible for the trial (please check).  
| R   |                                                                                                                                                                                                                                                                                                                  |
|-----|------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|
| 1.0 | Horv olcl is the patient'? (:' 18 ves of age) DOB: _t_ R*ce i\.lust circle .{l' LEAS'I one cltoice): American Lrclian .Lla.skan Natile Asian Black, Ati^icart Atueucatt \\l1rite Natir-e Hau'aiiau;olher Pacitlc Islaudet' Ethnicitlllrlrrst circle AT LEAST orte choice); Hispalic Non Hispanrc Gerrder: ]\{.'F |
| :0  | Does the pfltient ltave histologicall-v or cvtologicall.v confiflued cliagnosis of cttlaneotts nlelanoula that is considered tuu'esectable (Stage III or IV) ? (YESD(O) Stage : T:_N: lvl: (Note: s(age at strldy stalt) Date of Initial Diagnosit,  -i--l-.-..----                                              |
| la. | Does the patielrt have Oculat or lvlttcosal ulelanoura'? (No)                                                                                                                                                                                                                                                    |
| 4.0 | Does the patieut ltave nteasrtrable disease that is at least 20 mru by CT scau or::'10 rrun tbr spiral CT according to RECIST and WHO (rn\\iHo) 'l (Yes)                                                                                                                                                         |  
29 July 2015 Ver$ion: i.0 Protocol Versrorr Date T
Page l0l  
| Ptotocol: A Phase II Si0gle .A.nu Shrdy of Hislr-Dose IL-3 and Ipilimu*nb in Parients u:ith Llrresectable SraEe III and Stage Iv- Melaoorua Principal Inr.estigator Is the patient's life expectancy:: 3 rncutlx.? (\'es) 5.0 6.0 What is the patient's ECOG per-fonuanee statusi (0 r:r r) Date: ! ! 1.0 Is the patienl ar:cesrit:le and a[:le to cotnply witli lrealrneut. PK and iuunrute-ruorritoring sarrrple collection. alrd requiretl shrdy ttrllow-up? (yes) If the patient is a rvouran of ctrildtrearing pc,iiutial (WOCBP)- does she have a negative seturl or tuile pregrmncli test (rninirnunr sensilivitv l-f UI/L or equivalent units of H('G) rvithin T2 horus trefore the start of ipiliururratr. or Day I, rvhich is acceptable per the spon.sor '7 {l'esl NA- only' if the patieut is nmle or not of child bearing potential) 80 Date: ' I If the rvoman is a rvomel of NON-childbearurg   |
|----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
  
  
  
1,8({/.  
Ptotocol: A Phase II Single Amr Shrdy of High-Dose IL-? and Ipiliruurmb in Parienrs with LLuerectable Stage  
III and Stage I v* lulelanorui  
| III and Stage I v* lulelanorui Principal Iur-estigator: 9.0 I1'the patient is a WOC'ilP. does slre agrer. lo use fltr ar:ceptalrle rnethod of contraception to avoid preEnancy tluoughout the strrdy and fcrr at least 4 r.veeks prior to initiation of dmg and fbr at least 26 weeks atler the last close of iuvestigatioual prr:duct iu such a lrunuler that the risk of pregnancy is niiniruized'? (Yesr NA *orrly if the patieut is male or not of childbealing potettial) 10.0 If the patient is a sexrmlll,'active nrale, does he agree to use an acceptable urethod of contraceptiou tlu'ouEilrout the shrtiy aud tbr at least 4 rveek.s prior tt-r uritiatitu of the clmg and tbr at lea-st I rveeks atler the last dose of investieational product iu such a ruaruter. that the risk of pregualrc) is tnutiurized? (\'esO,iAorrly if the patient is a t'errrale) I 1.0 Is lhe patieut preeuaut or breasft'eeclurg? (No,?,lA-oulv if the patient is a rnale) 13.0 Does the patierrt have krrorru or srnpected lrrairr uletasta sis? (Yes,tlC)) 13.0 If Yes to I2.0, have the brain metaslases lreen prer,iously treated'J (Yes,.,).iA- onll..if the ansrver tt_r question 1{.0 is No) 14.0 If Yes to 12.0, has an Iv{RI rvith ald rvithr:r}l cc}nhast or CT of the trrain been perfbnued to nrle out trrain uretastases or lo xhow no errideuce of plogressiou for at least 4 weeks.) (\'esNA-onlv if the answer to question 14.0 is No) 15 0 If Yes to 12.0. has the pxrieut been otf iuuuturosuppressir.e doses of systeuric rnedicatiorx. at least .1 weeks al tiure of eruollnrent'? (Yes,liA-only if arlslver to questiou 14.0 is Nr:) it{ote: Corticosteloicls har,e a rvashcut period of l4 days prior to landornizatiou. 16.0 Does the piltient have prior nraliguancv actil.e i.vith the previous 5 I'ears? (No)   |
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| IulestisRtor: t 7.0 Does the paiieut liave aul,aclive auloiuunrure clisease or a docruuented hi$torv of auloinurrune disease'} (No) r8 0 Dr:es the patieut have a history of a syneh-oule that required systeuic sterord ol irrunuilosltppressive tnedit:atious'7 (No) Note: Sutrject rvith vitiligo . psr-rriasis ur active r.vithin the past 2 years . rcsolved childtrood astluua,'atopliy , or thyroid disease controlled trv replacement therapy without the need tor ituuunosuppressiou are eligible 19.0 Does the patlent har.e l:norvn or suspectecl humau inuuune deficiencv virus (Hi\J . hepatiti^s B or Cl infection? {No) 10.0 Does the patieut have or a histoly of exteusive prilmonary uretastases or cluodc puluonary disease history? ()rlo) Date: i l,lote' FE\II and FV( .,> 659.'0 Note: Onl_v frrr patieurs rvith pulmonary function: FEV1 and FVC > 650/o of prediction for those patients with extensive pulmonary metastases or chronic pu l_mgnary I j :Sa":"e_ h5lg-y, 22 0 Is the patierrt on beta-trlockers'J (Yes,No) Nate; Pntioilt,s t,t(tt be weotted qffoJ'beto-blockers fiuo x'eeks prior to sfidy enrollnrcnt wder tlrc supewision of thei.r prirnan' ccrdiologist. 23.0 Does the pafient have an rurderly.iug heart conclition and those 50 years or t'rlder rvho have reversible ischeuric change.s on cardiac stless test rvho are deeured ineligible for sru.gery by'cat'diolog.v consult? (No) Date of Clarcliac Stress Test: i' j 2.1.0 Has the patieut beeu treated rvith IL-3. ipilirnumatr or prior C'TLA-.Iilhibitor or agonist? (YesrNo) Note: not for rnetastatic clisease. :5.0 If ),es to 26.0. has rt beerr at leasl 6 months since the final adluvant treattuent trour stad of study tr.eatureut'J   |
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Plotocol: A Phase II Sirrgle Aru Shrdl'of High"Dose IL-l ancl Ipilinrurnab in Pa'tienrs wirh Uruerectable Srage III and Stage IV Melauorua IulestisRtor:  
| Plotocol: A Pha,re II Single Amr Study of High-Dose IL-1, ond lpilinruurab in Palients tvith Lkuerectable Srage IlI and Sraqe I\: \lelauortra I Iuvestigator: (\ esNA only if answered NO to 26.0) Date: _/--.'_ 2(r.0 If ves 1o 16.0 did the patierrt lrave Gracle -] or sreater at'lverse e\ieuts rvith prior adjuvaut rpilimurnab therapy that c{icl nol resolve with linritecl corticosteroid use'j (Nor NA onlf, if ansrvelecl N0 to 26.0) 27.0 Does the patient have preseuce of au underl_r,.iug uredical couditiorr that in the opirriou of the investisatol or Sponsor could adrrersely affect the atriliry.' of the sutrject to cornplv rvith or tolelate study procechres an<l'or snld)'therapl' 'l (No) 28.0 Does the patient have evidelce of organ dysiiurction or ar)y clirrically signiticant clevinfiou trout norltal irr phvsical examiualion. r,ital sigrrs. ECG or clirrieal latroratory def ennina tion.s treyorrd r.r,hn t i s c ous isteut rvith the ttirget populatiol? (No) 290 Has the patient been treated with systeuric anti-caucer treahneut (including investigation dtugs ) withil4 weeks of trst dose of study uredication? (No) Date of tast Treatnrent: I I 300 Has the patient treeu treated rvith iuuururo,suppressive meclicatious or iuununosuppressive closes ol systenic cr:r-ficosteroids (doses ::," lQ 1us:dcav predrusoue or equivalent) r,vithirr t4 days of fir'st dose of study uiedication? (lio) 33.0 Did the lratient have sulser_v or radiotherapv rvithin .1 rveeks prior to eruolhuenf rvithout anv sequelae of tlre eruollnreut of sfutll,' uredicatiou'? (I-io.1 33.0 Did the patienf har,e any ni:n-oncologv live viral vaccirre therapies used lor preventiou of intbctious clisease rvithin I monlh ol'the tirst dose of study uredicatic'rn? (No) 3.10 Dicl the patient have prior tl'eatment u,ith lpilimurrral:   |
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| Ptotocol: A Phase II Single .fu:u Shrdl' of Higlr-Dose IL-l and Ipilimunrab in Patients u,ith tlru'esectatrle Stage III and Stage IV \lelanoma Princrpal Inr^estigator or IL-2? (No) 3 5.0 FIas the patieut been treated rvith auti-CTLA a'? ().ir:) 36.0 Is the patient a prisnner or invohurtaril-v incarcerated? (No) 3 7.0 Is the llatient courg:ulsor-il,v detained for treaturent of eithel a psychiatric or ph.vsical (e g . irrfbctious disease) illness'l (No) 38.0 \14rat is the patients ANC'? (", 1000,lul-) Date: / / 390 What is the patient's platelet count? ( :: 75.000 rul-) Dale: _,_'_ Note: Transfasion lo achiew the required lewls resqectively is nol Permilted. 400 What is tlre patienl's Hernogk:birr? (19,0 ddl.) Date: i I Note: (180 g/L; tnol: fig lransfused) ,1 1.0 What is the patienl's lr:tal creatitiue'l (< 2.0 r ULN) Date: _  !_ .12 0 What is the patient's total lrilinrbin? (! 2.0 x LILN ) Date: _ l_ Does have patient Gilbert's Syrch-orrre? (Yes,t{o) Note: patients rvith Gilbert's Syndrorne. rvho must have a total bilir-ubin less than 3.0 msidl-) ,13.0 Wiral is tlte palieut's AST? (: :.S x ULN tbr patienls rvithout lir.er uretastasis. .., 5 tinres tbr patients with liver metastases) Date:--l_1-- 4d0 What is the patient's ALl"l (: Z.-s x ULN for patient.s rvithout liver uretastasis. < 5 tiures tbr patients rvith lir,er uretastases) Date: i I r15.0 is the lratient lvilling and able to lrlovide sigued mforrned conserlt. including conseul lirr al1' screeuiug proceclures corrducted to establish eligibility fr:r regrstratiou. requu'ecl prir-rr to trial particilration'? (Yes)   |
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Protocol: A Phase II Single .tu"rrr Shrdl'of Higlr-Dose IL-l and Ipiliuuorab in Parienrs u,ith LLuesectable Srase III and Stage IY lr{elanoun Principal hrr-estigator, f Team PII ,sician or Consentin Professional  
| Revierved and Approved by : (Print First and Last Name)                                   | Title:    |    |
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| Reviervecl aucl Approvecl tr1,: (siguatue)                                                | Date: _l_ | I  |
| By signing above I attest that I have rer.iewed aud coufinnecl that the atrove [:eeu uret |           |    |
Clinical trial: NCT02203604
Section: Withdrawal from Study
Subsections: Also Rvithdrarv Collseut Fbr The Use Of U Data. But Uumt Clo This Il R.Vri You To Dr.

fury data that has already beeu collected camot be rvithtlrawr because therc umy not be aly identifiers to link the data with you. We ale required by the Food zurd Dnrg Achninishation horvever. to contiuue to report anything that relates t<l the safety of these clnrgs.  
At any tiure. the study doctor can take you orrf of this stldy because it would uot be in your best interest to stay in it. Your study doctor can stop treatmeut eveu if you are rvilling to stay in the shrdy.  
If you decide to withdraw fi'orn the shrdy for aily reason. you uny be asked to retum for at least one aclditional visit lbr sat'ety reasors.  
Who can you call if you have any questions?  
If you have any questiorrs abr:ut taking part in this study or if you feel yotr utay have suffered a research related in:ury. you can call the srudy doctor; I have auv questlons alrout -1,'orr rights as a research subject- you cau call:
What rre your rights if 1'ou tlecide to take part in this research stutty?  
You have the right to ask questious about any pzut of the srudy at ary time. You should not sipr this forxr urless you have had a ctnuce 1o ask questious aud have beerr given aus\vers to all of y'oru' qnestions.