E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Lymphocytic Leukemia (CLL) |
Kronična limfocitna leukemija |
|
E.1.1.1 | Medical condition in easily understood language |
Chronic Lymphocytic Leukemia (CLL) |
Kronična limfocitna leukemija |
|
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 | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10008958 |
E.1.2 | Term | Chronic lymphocytic leukaemia |
E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the effect of the addition of idelalisib to
bendamustine/rituximab on progression-free survival (PFS) in
subjects with previously treated chronic lymphocytic leukemia
(CLL) |
Procijeniti učinak dodatka idelalisiba (prethodno GS-1101) bendamustinu/rituksimabu na preživljenje bez progresije bolesti (PFS) u ispitanika s prethodno liječenom kroničnom limfocitnom leukemijom (KLL) |
|
E.2.2 | Secondary objectives of the trial |
• To determine the effect of the addition of idelalisib to bendamustine/rituximab on the onset, magnitude, and duration of tumor control
• To assess the effect of the addition of idelalisib to
bendamustine/rituximab on measures of subject well-being, including overall survival (OS), health-related quality of life (HRQL), and performance status
• To assess the effects of the addition of idelalisib to bendamustine/rituximab on disease associated biomarkers and to evaluate potential mechanisms of resistance to idelalisib
• To characterize the effect of bendamustine/rituximab on idelalisib exposure through evaluations of idelalisib plasma concentration over time
• To describe the safety profile observed with the addition of idelalisib to bendamustine/rituximab
• To estimate health resource utilization associated with the addition of idelalisib to bendamustine/rituximab |
• Procijeniti učinak dodatka idelalisiba bendamustinu/rituksimabu na nastup, opseg i trajanje kontrole tumora
• Procijeniti učinak dodatka idelalisiba bendamustinu/rituksimabu na mjere dobrobiti ispitanika uključujući ukupno preživljavanje (OS), kvalitetu života sa zdravstvenog gledišta (HRQL) i opće stanje bolesnika
• Procijeniti učinke dodatka idelalisiba bendastuminu/rituksimabu na biomarkere povezane s bolešću te procijeniti potencijalne mehanizme otpornosti na idelalisib
• Okarakterizirati učinak bendamustina/rituksimaba na izloženost idelalisibu putem procjena koncentracija idelalisiba u plazmi tijekom vremena
• Opisati promatrani sigurnosni profil kod dodatka idelalisiba bendamustinu/rituksimabu
• Procijeniti korištenje zdravstvenih resursa povezanih s dodatkom idelalisiba bendamustinu/rituksimabu
|
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1) Male or female ≥18 years of age.
2) Diagnosis of B-cell CLL, with diagnosis established according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria and documented within medical records.
3) CLL that warrants treatment (consistent with accepted IWCLL criteria for initiation of therapy)
4) Presence of measurable lymphadenopathy (defined as the presence of ≥1 nodal lesion that measures ≥2.0 cm in the longest diameter [LD] and ≥1.0 cm in the longest perpendicular diameter [LPD] as assessed by computed tomography [CT] or magnetic resonance imaging [MRI]).
5) Prior treatment for CLL comprising:
a) ≥2 cycles of a regimen containing a purine analog (eg. fludarabine, pentostatin, cladribine) or bendamustine, and
b) ≥2 doses with a regimen containing an anti-CD20 monoclonal antibody (eg. rituximab, ofatumumab, GA-101)
6) Documentation of CLL progression <36 months since the completion of the last prior therapy for CLL.
7) Discontinuation of all therapy (including radiotherapy, chemotherapy, immunotherapy, or investigational therapy) for the treatment of CLL ≥3 weeks before randomization. Note subjects may receive corticosteroids to manage CLL manifestations.
8) All acute toxic effects of any prior antitumor therapy resolved to Grade ≤1 before randomization (with the exception of alopecia [Grade 1 or 2 permitted], neurotoxicity [Grade 1 or 2 permitted], or bone marrow parameters [Grades 1 or 2 permitted]).
9) Karnofsky performance score of ≥60
10) Required baseline laboratory data (within 4 weeks prior to randomization) as shown in the protocol
11) For female subjects of childbearing potential, willingness to use a protocol-recommended method of contraception from the screening visit (Visit 1) throughout the study treatment period and for 30 days following the last dose of study drug or > 12 months from she last dose of rituximab (whichever is later). Note: A female subject is considered to be of childbearing potential unless she has had a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy; has medically documented ovarian failure (with serum estradiol and folliclestimulating hormone [FSH] levels within the institutional postmenopausal range and a negative serum or urine βHCG); or is menopausal (defined as age ≥ 54 with amenorrhea for >12 months or amenorrhea for >6 months with serum estradiol and FSH levels within the institutional postmenopausal range)
12) For male subjects of childbearing potential having intercourse with females of childbearing potential, willingness to use a protocol-recommended method of contraception from the randomization visit (Visit 2) throughout the study treatment period until ≥6 months following the last dose of bendamustine or ≥90 days following the last dose of study (whichever is later) and to refrain from sperm donation from randomization (Visit 2) throughout the study and until ≥6 months following the last dose of bendamustine or ≥90 days following the last dose of study drug (whichever is later). Note: A male subject is considered able to father a child unless he has had a bilateral vasectomy with documented aspermia or a bilateral orchiectomy, or has ongoing testicular suppression with a depot luteinizing hormone- releasing hormone (LH-RH) agonist (eg. goserelin acetate [Zoladex®]), leuprolide acetate [Lupron®]), or triptorelin pamoate [Trelstar®]).
13) In the judgment of the investigator, participation in the protocol offers an acceptable benefit-to-risk ratio when considering current CLL disease status, prior treatment history, medical condition, and the potential benefits and risks of alternative treatments for CLL.
Note: Investigators should consider whether a study subject is an
appropriate candidate for bendamustine-containing therapy based
on the number and severity of comorbid conditions; subjects with
a baseline Cumulative Illness Rating Scale (CIRS) score of ≤6
may be particularly appropriate candidates for this trial
14) Willingness and ability to comply with scheduled visits, drug administration plan, imaging studies, laboratory tests, other study procedures, and study restrictions. Note: Psychological, social, familial, or geographical factors that might preclude adequate study participation should be considered.
15) Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential benefits, possible side effects, potential risks and discomforts, and other pertinent aspects of study participation.
|
1) Muške ili ženske osobe ≥18 godina
2) Dijagnoza KLL-a B-stanica, s dijagnozom utvrđenom prema kriterijima Međunarodne radne skupine za kroničnu limfocitnu leukemiju i dokumentiranom u sklopu medicinske dokumentacije.
3) KLL koja zahtijeva liječenje (dosljedno prihvaćenim kriterijima IWCLL-a za početak terapije). Sva navedena stanja označavaju KLL za koji se zahtijeva liječenje:
a)Dokazano progresivno zatajenje koštane srži koje se manifestira pogoršanjem anemije i/ili trombocitopenije, ili
b)Teška (tj. donji rub slezene ≥6 cm ispod lijevog rebrenog luka), progresivna ili simptomatska splenomegalija, ili
c)Teška (tj. ≥10 cm u najduljem promjeru), progresivna ili simptomatska limfadenopatija, ili
d)Progresivna limfocitoza bez infekcije, uz povećanje ukupnog broja limfocita (ALC) ≥50% tijekom dvomjesečnog razdoblja ili vrijeme udvostručenja broja limfocita u krvi <6 mjeseci (sve dok je početni ALC bio ≥30.000/µl), ili
e)Autoimuna anemija i/ili trombocitopenija koja slabo reagira na kortikosteroide ili drugo standardno liječenje, ili
f)Konstitutivni simptomi definirani kao jedan ili više sljedećih simptoma ili znakova povezanih s bolesti koji se pojavljuju u odsutnosti dokaza infekcije:
i)Nenamjerni gubitak tjelesne težine od ≥10% u prethodnih 6 mj, ili
ii)Značajan umor (≥2. stupnja), ili
iii)Povišena temperatura >38,0 °C tijekom ≥2 tjedna, ili
iv)Noćno znojenje tijekom >1 mj.
4)Prisutnost mjerljive limfoadenopatije (definirane kao prisutnost ≥1 nodalne lezije veličine ≥2,0 cm u najduljem promjeru [LD] i ≥1,0 cm u najduljem okomitom promjeru prema procjeni kompjutorizirane tomografije [CT] ili snimanju magnetskom rezonancijom ).
5)Prethodno liječenje KLL-a koje se sastoji od:
a)≥2 ciklusa režimom koji sadrži purinski analog (npr. fludarabin, pentostatin, kladribin) ili bendamustin, i
b)≥2 doze režimom koji sadrži anti-CD20 monoklonalno protutijelo (npr. rituksimab, ofatumumab, GA-101)
6)Dokumentacija progresije KLL-a <36 mj nakon završetka zadnje prethodne terapije za KLL.
7)Potpuni prekid terapije (uključujući radioterapiju, kemoterapiju, imunoterapiju ili ispitivanu terapiju) za liječenje KLL-a ≥3 tjedna prije slučajnog odabira.
8)Svi akutni toksični učinci bilo koje prethodne antitumorske terapije riješeni do stupnja ≤1 prije slučajnog odabira (s iznimkom alopecije (gubitka kose) [dopušteni stupanj 1 ili 2], neurotoksičnosti [dopušteni stupanj 1 ili 2] ili parametara koštane srži [dopušteni stupanj 1 ili 2]).
9)Procjena općeg stanja po Karnofsky ljestvici ≥60.
10)Tražene početne lab. vrijednosti (unutar 4 tjedna prije slučajnog odabira) prema prikazu u sljedećoj tablici.
11) Za ispitanice u reproduktivnoj dobi, pristanak na korištenje metode kontracepcije preporučene planom ispitivanja od posjeta probira (1. posjet) kroz cijelo ispitivanje i 30 dana nakon zadnje doze ispitivanog lijeka ili >12 mj nakon zadnje doze rituksimaba (što god od toga je kasnije). Napomena: Smatra se da je ispitanica u reproduktivnoj dobi osim ako je imala histerektomiju, obostrano podvezivanje jajnika ili obostrano odstranjivanje jajnika (ooforektomija); ima medicinski dokumentirano zatajenje jajnika (sa serumskim estradiolom i hormonom za stimulaciju folikula u razinama unutar službenog raspona za postmenopauzu i negativan βHCG u serumu ili urinu); ili je u menopauzi (amenoreja tijekom >12 mjeseci ili amenoreja tijekom >6 mjeseci sa serumskim estradiolom i razinama FSH-a unutar službenog raspona za postmenopauzu).
12)Za ispitanike u reproduktivnoj dobi koji imaju spolni odnos sa ženama u reproduktivnoj dobi, pristanak na korištenje metode kontracepcije preporučene planom ispitivanja od posjeta za slučajni odabir (2. posjet), kroz cijelo ispitivanje i do >6 mj nakon zadnje doze bendamustina ili >90 dana nakon zadnje doze ispitivanog lijeka (što god od toga je kasnije), te ustezanje od doniranja sperme od slučajnog odabira (2. posjet), kroz cijelo ispitivanje i do >6 mj nakon zadnje doze bendamustina ili >90 dana nakon zadnje doze ispitivanog lijeka (što god od toga je kasnije).
13)Prema procjeni ispitivača sudjelovanje u planu ispitivanja omogućuje prihvatljiv omjer koristi spram rizika razmatrajući trenutno stanje KLL bolesti, prethodnu povijest liječenja, zdravstveno stanje i potencijalne koristi i rizike alternativnih liječenja KLL-a.
14)Pristanak i sposobnost pridržavanja planu zakazanih posjeta, plana uzimanja lijekova, ispitivanja snimanjem, laboratorijskih pretraga te ostalih postupaka i ograničenja u ispitivanju.
15)Dokaz o vlastoručno potpisanom informiranom pristanku u kojem je vidljivo da je ispitanik svjestan neoplastične naravi bolesti te da je informiran o procedurama koje treba slijediti, eksperimentalnoj naravi terapije, alternativnim načinima, potencijalnim koristima, mogućim nuspojavama, potencijalnim rizicima i neugodama te ostalim pripadajućim aspektima sudjelovanja u ispitivanju.
|
|
E.4 | Principal exclusion criteria |
1) Known histological transformation from CLL to an aggressive lymphoma
(ie, Richter transformation). Note: Biopsy documentation of the absence or presence of transformation is not required.
2) Known presence of intermediate- or high-grade myelodysplastic syndrome
(ie, subjects are excluded who have ≥5% bone marrow blasts; karotypic abnormalities other than normal, Y deletion, 5q deletion, or 20q deletion; or ≥2 lineages of cytopenias due to myelodysplasia).
3) History of a non-CLL malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate-specific antigen for ≥1 year prior to randomization, other adequately treated Stage 1 or 2 cancer currently in complete remission, or any other cancer that has been in complete remission for ≥5 years.
4) Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of randomization (Visit 2). Note: Subjects with localized fungal infections of skin or nails are eligible. Subjects may be receiving prophylactic antiviral or antibacterial therapies at the discretion of the investigator. For subjects who are at substantial risk of an infection (eg, influenza) that may be prevented by immunization, consideration should be given to providing the vaccine prior to initiation of protocol therapy.
5) Ongoing drug-induced liver injury, chronic active hepatitis C (HCV), chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
6) Ongoing drug-induced pneumonitis.
7) Ongoing inflammatory bowel disease.
8) Ongoing alcohol or drug addiction.
9) Pregnancy or breastfeeding.
10) History of prior allogeneic bone marrow progenitor cell or solid organ transplantation.
11) Ongoing immunosuppressive therapy other than corticosteroids Note: Subjects may use topical, enteric, inhaled, or systemic corticosteroids as therapy for manifestations of CLL, comorbid conditions, or autoimmune anemia and/or thrombocytopenia. During study participation, subjects may receive systemic or other corticosteroids as pretreatment for rituximab infusions or as needed for treatment-emergent comorbid conditions.
12) In a subject with a history of prior bendamustine therapy, a time interval from the last dose of bendamustine to the subsequent CLL progression of <6 months.
13) History of prior therapy with any inhibitor of AKT, Bruton tyrosine kinase (BTK), Janus kinase (JAK), mammalian target of rapamycin (mTOR), phosphatidylinositol 3 kinase (PI3K) (including idelalisib), or spleen tyrosine kinase (SYK).
14) History of anaphylaxis in association with previous administration of monoclonal antibodies.
15) Concurrent participation in another therapeutic clinical trial.
16) Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject or impair the assessment of study results. |
Kriteriji za neuključivanje
Ispitanik koji ispunjava bilo koji od sljedećih kriterija neuključivanja ne smije se uključiti u ovo ispitivanje:
1) Poznata histološka transformacija KLL-a u agresivni limfom (npr. Richterova transformacija). Napomena: Dokumentacija biopsije o neprisutnosti ili prisutnosti transformacije nije potrebna.
2) Poznata prisutnost srednjeg ili visokog stupnja mijelodisplastičnog sindroma (tj. neuključivanje ispitanika koji imaju ≥5% blasta koštane srži; kariotipske abnormalnosti osim uobičajenih, deplecija Y, deplecija 5q ili deplecija 20q; ili ≥2 loze citopenije uzrokovane mijelodisplazijom).
3) Povijest maligniteta koji nije povezan s KLL-om osim sljedećeg: adekvatno liječenog lokalnog karcinoma bazalnih stanica kože ili planocelularnog karcinoma, karcinoma grlića maternice in situ, površinskog karcinoma mokraćnog mjehura, asimptomatskog karcinoma prostate bez poznate metastatske bolesti bez zahtijevane terapije ili samo uz zahtjev hormonalne terapije te uz normalan prostata specifični antigen za prostatu tijekom ≥1 godine prije slučajnog odabira, ostali odgovarajuće liječeni karcinomi 1. ili 2. stadija koji su trenutačno u potpunoj remisiji ili bilo koji drugi rak koji je u potpunoj remisiji već ≥5 godina.
4) Dokaz o sistemskoj bakterijskoj, gljivičnoj ili virusnoj infekciji u tijeku u vrijeme slučajnog odabira (2. posjet). Napomena: Ispitanici s lokaliziranim gljivičnim infekcijama kože ili noktiju su podobni. Ispitanici mogu primati profilaktičku antivirusnu ili antibakterijsku terapiju prema procjeni ispitivača. Za ispitanike kod kojih postoji značajan rizik od infekcije (npr. gripa) koja se može spriječiti imunizacijom, treba se razmotriti cijepljenje prije početka terapije iz plana ispitivanja.
5) Trenutačno oštećenje jetre izazvano lijekovima, kronični aktivni hepatitis C (HCV), kronični aktivni hepatitis B (HBV), alkoholna bolest jetre, nealkoholni steatohepatitis, primarna bilijarna ciroza, ekstrahepatička opstrukcija uzrokovana kolelitijazom, ciroza jetre ili portalna hipertenzija.
6) Trenutačni pneumonitis izazvan lijekovima.
7) Trenutačna upalna bolest crijeva.
8) Trenutačna ovisnost o alkoholu ili drogama.
9) Trudnoća ili dojenje.
10) Povijest prethodne alogene transplantacije koštane srži ili tvrdih organa.
11) Trenutačna terapija imunosupresivima osim kortikosteroida. Napomena: Ispitanici mogu uzimati topikalne, enteričke, inhalacijske ili sistemske kortikosteroide kao terapiju za manifestacije KLL-a, pratećih stanja ili autoimune anemije i/ili trombocitopenije. Tijekom sudjelovanja u ispitivanju ispitanici mogu primati sistemske ili druge kortikosteroide kao pripremno liječenje koje prethodi infuzijama rituksimaba ili prema potrebi za prateća stanja uzrokovana lijekovima.
12) U ispitanika koji su prethodno liječeni bendamustinom, vremenski razmak od zadnje doze bendamustina do uzastopne progresije KLL-a tijekom <6 mjeseci.
Povijest prethodne terapije bilo kojim inhibitorom AKT-a, Bruton tirozin-kinazom (BTK), Janus kinazom (JAK), ciljnim molekulama rapamicina u sisavaca (mTOR), fosfatidilinozitol 3-kinazom (PI3K) (uključujući idelalisib) ili tirozin-kinazom u slezeni (SYK).
14) Povijest anafilakse povezane s prethodnom primjenom monoklonskih protutijela.
15) Istodobno sudjelovanje u drugom terapijskom kliničkom ispitivanju.
16) Prethodna ili trenutačna klinički značajna bolest, zdravstveno stanje, kirurška povijest, fizikalni nalaz, nalaz elektrokardiograma (EKG) ili laboratorijska anomalija koja bi prema mišljenju ispitivača mogla negativno utjecati na sigurnost ispitanika ili ugroziti procjenu rezultata ispitivanja
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Progression-free survival (PFS) – defined as the interval from randomization to the earlier of the first documentation of definitive disease progression or death from any cause; definitive disease progression is CLL progression based on standard criteria and occurring for any reason (ie, increasing lymphadenopathy,
organomegaly or bone marrow involvement; decreasing platelet count, hemoglobin, or neutrophil count; or worsening of disease-related symptoms) other than lymphocytosis alone |
Preživljenje bez progresije bolesti (PFS) - definirano kao vremenski razmak od slučajnog odabira do najranije prve dokumentirane definitivne progresije bolesti ili smrti uzrokovane bilo kojim razlogom; definitivna progresija bolesti je progresija KLL-a temeljena na standardnim kriterijima, osim same limfocitoze |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Clinic/laboratory visits will occur every 2 weeks through Week 24 and every 6 weeks between Weeks 24 and 48. Subjects who continue on study treatment past Week 48 will have clinic visits every 12 weeks. Subjects will be assessed for safety at each clinic visit. Subjects will be assessed for CLL disease status by physical and laboratory examinations at each clinic visit and by CT or MRI at Weeks 12, 24, 36, and 48 and every 12 weeks thereafter. |
Posjete ispitanika biti će svaka 2 tjedna do Tjedna 24 te svakih 6 mjeseci između Tjedna 24 i 48. Ispitanici koji nastave s terapijskom fazom nakon Tjedna 48 obavljat će posjete svakih 12 tjedana u svrhu procjene sigurnosti. Procjena bolesti fizikalnim pregledom te laboratorijskim pretragama te CT-om ili MRI-om biti će rađena tijekom posjeta na Tjednima 12, 24, 36 te 48 te potom svakih 12 tjedana. |
|
E.5.2 | Secondary end point(s) |
- ORR – defined as the proportion of subjects who achieve a CR or partial response (PR)
- Lymph node response rate – defined as the proportion of subjects who achieve a ≥50% decrease from baseline in the SPD of index lesion
- CR rate – defined as the proportion of subjects who achieve a CR
- Time to response (TTR) – defined as the interval from randomization to the first documentation of CR or PR |
• Stopa ukupnog odgovora (ORR) – definirana kao udio ispitanika koji postižu potpuni odgovor (CR) ili djelomičan odgovor (PR)
• Stopa odgovora limfnih čvorova – definirana kao udio ispitanika koji postižu ≥50% smanjenja najvećeg okomitog promjera (SPD) indeksiranih lezija u odnosu na početnu vrijednost
• Stopa CR-a - definirana kao udio ispitanika koji postižu CR
• Vrijeme odgovora (TTR) – definirano kao vremensko razdoblje od slučajnog odabira do prvog dokumentiranog kompletnog ili djelomičnog odgovora (CR ili PR).
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Clinic/laboratory visits will occur every 2 weeks through Week 24 and every 6 weeks between Weeks 24 and 48. Subjects who continue on study treatment past Week 48 will have clinic visits every 12 weeks. Subjects will be assessed for safety at each clinic visit. Subjects will be assessed for CLL disease status by physical and laboratory examinations at each clinic visit and by CT or MRI at Weeks 12, 24, 36, and 48 and every 12 weeks thereafter. For follow-up visits after Week 120, CT or MRI is only required at the End-of-Treatment visit. |
Posjete ispitanika biti će svaka 2 tjedna do Tjedna 24 te svakih 6 mjeseci između Tjedna 24 i 48. Ispitanici koji nastave s terapijskom fazom nakon Tjedna 48 obavljat će posjete svakih 12 tjedana u svrhu procjene sigurnosti. Procjena bolesti fizikalnim pregledom te laboratorijskim pretragama te CT-om ili MRI-om biti će rađena tijekom posjeta na Tjednima 12, 24, 36 te 48 te potom svakih 12 tjedana.
Za posjete praćenja nakon Tjedna 120, CT ili MRI biti će obvezan samo tijekom Posjete vezane za završetak terapije. |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | Yes |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 99 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Austria |
Belgium |
Brazil |
Canada |
Croatia |
Czech Republic |
France |
Germany |
Greece |
Hungary |
Ireland |
Israel |
Italy |
New Zealand |
Poland |
Portugal |
Romania |
Russian Federation |
Spain |
Turkey |
Ukraine |
United Kingdom |
United States |
|
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
|
It is expected that the final analysis of the study will take place after a minimum of 24 months of follow-up. The final analysis will be conducted after the 260th event (definitive CLL progression or death) or 36 months from the time the last subject is enrolled (whichever occurs first). Once outstanding data queries have been resolved, the database will be locked, the blind will be broken, and the final analysis of the study will be performed. |
Očekuje se da će konačna analiza ispitivanja biti naprvaljena nakon najmanje 24 mjeseca praćenja. Konačna analiza napraviti će se nakon 260-og događaja (definitivne progresije bolesti ili smrti) ili 36 mjeseci od dana kada je zadnji ispitanik uključen u ispitivanje (ovisno što prije od navedenog nastupi). Nakon rješavanja svih diskrepanci test-liste baza podataka biti će zatvorena, ispitivanje odslijepljeno te će se napravit konačna analiza. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 4 |
E.8.9.1 | In the Member State concerned months | 8 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |