E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Follicular Lymphoma |
Linfoma follicolare |
|
E.1.1.1 | Medical condition in easily understood language |
Blood cancer |
Tumore del sangue |
|
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 | 14.1 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10025320 |
E.1.2 | Term | Lymphomas non-Hodgkin's B-cell |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
|
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 |
The primary objective of the study is to evaluate the ORR of PCI-32765, as assessed by the Independent Review Committee (IRC), in subjects with chemoimmunotherapy-resistant FL |
L'obiettivo principale dello studio è valutare il tasso di risposta globale di PCI-32765, secondo la valutazione del Comitato di revisione indipendente (IRC), in soggetti con linfoma follicolare resistente alla chemio-immunoterapia. |
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E.2.2 | Secondary objectives of the trial |
Evaluate the duration of response Evaluate the safety |
Valutazione della durata della risposta Valutazione della sicurezza di PCI327656 |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1 Histologic proof of Grade 1, 2, or 3a follicular lymphoma (FL) without clinical or pathological evidence of transformation 2 Previously treated with at least 2 prior lines of therapy, including at least 1 rituximab combination chemotherapy regimen; last prior line of therapy includes an anti CD20 monoclonal antibody-containing chemotherapy regimen (separate lines of therapy are defined as different regimens that are either separated by disease progression, refractory disease, or relapsed disease) 3 Resistant disease to the last therapy, defined as progression of disease during or within 12 months of the last dose of a CD20 antibody combination chemotherapy regimen 4 At least 1 measurable site of disease according to International Working Group Revised Response Criteria for Malignant Lymphoma 5 Eastern Cooperative Oncology Group performance status grade 0 or 1 6 Hematology and biochemical laboratory values must be within protocol defined parameters within 7 days prior to enrollment 7 Agrees to protocol-defined use of effective contraception 8 Women of childbearing potential must have a negative serum or urine pregnancy test at screening |
1. Prova istologica di linfoma follicolare di grado 1, 2 o 3a senza evidenza clinica o patologica di trasformazione. 2. Precedente trattamento con almeno due linee di terapia precedenti con almeno un precedente regime chemioterapico contenente rituximab; ultima linea di terapia precedente inclusiva di un regime chemioterapico contenente un anticorpo monoclonale anti-CD20 (per linee di terapia distinte si intendono regimi diversi intervallati dalla progressione della malattia, dalla malattia refrattaria o da una recidiva). 3. Malattia resistente all'ultima terapia precedente, definita come progressione della malattia durante o entro 12 mesi dall'ultima dose di un regime chemioterapico comprendente un anticorpo anti-CD20. 4. Almeno 1 sede misurabile della malattia secondo i criteri di risposta revisionati per il linfoma maligno secondo il International Working Group 5. Stato di performance secondo Eastern Cooperative Oncology Group di grado 0 or 1 6. I valori ematologici e biochimici devono essere compresi entro i limiti definiti dal protocollo ed entro i 7 giorni precedenti all'arruolamento. 7. Accettazione di misure contraccettive altamente efficaci come da protocollo. 8. Le donne in età fertile devono presentare un test di gravidanza sul siero o sulle urine negativo allo screening. |
|
E.4 | Principal exclusion criteria |
1 Prior nitrosoureas within 6 weeks, chemotherapy within 3 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxinimmunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, or major surgery within 4 weeks of first dose of study drug 2 Prior treatment with PCI-32765, other Bruton's tyrosine kinase inhibitors, or phosphoinositide 3-kinase delta inhibitors 3 Concurrent enrollment in another therapeutic investigational clinical treatment study 4 Received a prior allogeneic hematopoietic stem cell transplant (prior autologous hematopoietic stem cell transplant is allowed) 5 Known central nervous system lymphoma 6 History of prior malignancy except: a) malignancy treated with curative intent and with no known active disease present for >=3 years before enrollment; b) adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; c) adequately treated cervical carcinoma in situ wit hout evidence of disease) 7 History of stroke or intracranial hemorrhage within 6 months prior to enrollment 8 Requires anticoagulation with warfarin or equivalent vitamin K antagonists 9 Requires treatment with strong cytochrome P450 (CYP)3A4/5 inhibitors 10 Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification 11 Known history of Human Immunodeficiency Virus (HIV) or Hepatitis C or active infection with Hepatitis B or any uncontrolled active systemic infection requiring intravenous antibiotics 12 Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of PCI- 32765 capsules, or put the study outcomes at undue risk |
1. Precedente trattamento con nitrosuree nelle 6 settimane precedenti, chemioterapia nelle 3 settimane precedenti, immunoterapia antitumorale nelle 4 settimane precedenti, terapia con radioimmunoconiugati o immunotossine nelle 10 settimane precedenti, radioterapia o altri agenti sperimentali nelle 3 settimane precedenti o intervento chirurgico di rilievo nelle 4 settimane precedenti alla prima somministrazione del farmaco dello studio. 2. Precedente trattamento con PCI-32765, altri inibitori di BTK o inibitori di PI3K delta. 3. Arruolamento contemporaneo in un altro studio clinico sperimentale terapeutico. 4. Precedente trapianto allogenico di cellule staminali ematopoietiche (è consentito un precedente trapianto autologo di cellule staminali ematopoietiche). 5. Linfoma noto del sistema nervoso centrale. 6. Precedente storia di neoplasia, ad eccezione di: a. neoplasia trattata con intento curativo e assenza di malattia attiva nota negli ultimi 3 anni prima dell'arruolamento; b. cancro della pelle diverso dal melanoma o lentigo maligna adeguatamente trattati senza evidenza di malattia; c. carcinoma cervicale in situ adeguatamente trattato senza evidenza di malattia. 7. Anamnesi di ictus o emorragia intracranica entro i 6 mesi precedenti all'arruolamento. 8. Necessità di terapia anticoagulante con warfarin o antagonisti della vitamina K equivalenti 9. Necessità di trattamento con forti inibitori del citocromo P450 (CYP)3A4/5. 10. Malattia cardiovascolare clinicamente significativa, come aritmie sintomatiche o non controllate, insufficienza cardiaca congestizia o infarto del miocardio nei 6 mesi precedenti allo screening, o altra malattia cardiaca di classe 3 (moderata) o classe 4 (grave) secondo la definizione della New York Heart Association Functional Classification. 11. Anamnesi nota di infezione da virus dell'immunodeficienza umana (HIV) o epatite C o infezione attiva da virus dell'epatite B o qualsiasi altra infezione sistemica attiva non controllata che richieda la somministrazione di antibiotici per via endovenosa.
12. Donne in gravidanza o allattamento. 13 Qualsiasi patologia, condizione medica o disfunzione degli organi potenzialmente fatale che, secondo il giudizio dello sperimentatore, potrebbe compromettere la sicurezza del soggetto, interferire con l'assorbimento o il metabolismo delle capsule di PCI-32765 o mettere inutilmente a rischio i risultati dello studio. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Overall response rate |
Tasso di risposta generale |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
Time frame = every 12 weeks during the first 24 months, followed by every 24 weeks thereafter until disease progression (up to 2 years after the last patient is enrolled) |
Ogni 12 settimane durante i primi 24 mesi, poi ogni 24 settimane fino a progressione di malattia (fino a 2 anni dopo l'ultimo paziente arruolato) |
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E.5.2 | Secondary end point(s) |
Duration of response |
Durata della risposta |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Time frame = every 12 weeks during the first 24 months, followed by every 24 weeks thereafter until disease progression (up to 2 years after the last patient is enrolled) |
Ogni 12 settimane durante i primi 24 mesi, poi ogni 24 settimane fino a progressione di malattia (fino a 2 anni dopo l'ultimo paziente arruolato) |
|
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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Biomarker analysis |
Analisi dei biomarcatori |
|
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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) | 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 | 1 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 33 |
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 |
Australia |
Russian Federation |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 43 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 43 |
E.8.9.2 | In all countries concerned by the trial days | 0 |