Zusammenfassende Beschreibung der Studie (Datenquelle: BASEC)
Lo scopo dello studio è quello di esaminare il farmaco sperimentale denominato ME-401; tale farmaco non è ancora disponibile né sul mercato svizzero né in altri paesi. ME-401 è oggetto di sviluppo come potenziale trattamento per diversi tipi di linfoma e di leucemia, ovvero forme tumorali che influiscono su linfociti, cellule immunitarie presenti nel sangue, linfonodi e altri organi. Lo studio è stato concepito per valutare la sicurezza di ME-401, la capacità dell’organismo di tollerare il medicinale, la possibile efficacia del farmaco e il modo in cui l’agente viene metabolizzato dal corpo umano. ME-401 viene assunto per via orale una volta al giorno, fino a quando il paziente ne trarrà beneficio clinico e fino a che non manifesti tossicità grave.
Untersuchte Krankheiten(Datenquelle: BASEC)
Diagnosi di leucemia linfatica cronica (Chronic Lymphocytic Leukemia, CLL), linfoma linfocitico a piccole cellule (Small Lymphocytic Lymphoma, SLL) o linfoma follicolare (Follicular Lymphoma, FL) recidivante o refrattario.
I pazienti devono soddisfare i seguenti criteri per la malattia recidivante o refrattaria:
- Malattia recidivante: paziente che ha precedentemente ottenuto una risposta completa o parziale, ma ha evidenziato progressione della malattia dopo una risposta di durata > 6 mesi.
- Malattia refrattaria: paziente che ha evidenziato progressione della malattia entro 6 mesi dalla terapia più recente.
Health conditions
(Datenquelle: WHO)
Chronic Lymphocytic Leukemia (CLL);Small Lymphocytic Lymphoma (SLL);Follicular Lymphoma (FL);Marginal Zone B Cell Lymphoma;Diffuse Large B-cell Lymphoma (DLBCL);High Grade Non-Hodgkin's Lymphoma;Mantle Cell Lymphoma (MCL)
Seltene Krankheit
(Datenquelle: BASEC)
Nein
Untersuchte Intervention (z.B. Medikament, Therapie, Kampagne)
(Datenquelle: BASEC)
Nell’ambito dello studio i pazienti verranno assegnati a uno dei sette livelli posologici (coorti) previsti di ME-401. Il medicinale verrà somministrato con cadenza giornaliera sotto forma di capsule. Prima di arruolare i pazienti nella coorte successiva, il medico dello studio e altri membri del personale della ricerca valuteranno la sicurezza del farmaco sperimentale all’interno della coorte attuale e di quelle precedenti. La durata della somministrazione del trattamento sperimentale dipenderà dalla capacità dei pazienti di tollerare la terapia assegnata e dall’effetto esercitato sul tumore.
Interventions
(Datenquelle: WHO)
Drug: ME-401;Drug: Rituximab;Drug: Zanubrutinib
Kriterien zur Teilnahme an der Studie
(Datenquelle: BASEC)
-Alla sperimentazione possono accedere pazienti di ambo i sessi che abbiano sottoscritto il modulo di consenso informato dello studio e che soddisfino tutti i criteri di inclusione e nessuno dei criteri di esclusione. I principali criteri di inclusione annoverano quanto segue:
- Diagnosi di CLL e/o SLL o FL recidivanti/refrattari.
- Nessuna terapia pregressa con medicinali simili (inibitori della fosfatidilinositolo 3-chinasi-d [PI3Kd]).
- Nessuna terapia pregressa con inibitori della Bruton tirosin chinasi (BTK), fatta salva l’eventualità in cui il soggetto fosse intollerante alla terapia BTK.
Ausschlusskriterien
(Datenquelle: BASEC)
I principali criteri di esclusione annoverano quanto segue:
- Trasformazione istologica attiva nota da CLL a un linfoma aggressivo.
- Qualsiasi malattia non controllata tra cui, a mero titolo esemplificativo, infezioni attive significative, ipertensione, angina, aritmie, pneumopatia o disfunzione autoimmune (in particolare anemia emolitica autoimmune o trombocitopenia immune).
- Altra diagnosi di tumore maligno che necessiterà presumibilmente di trattamento nei 2 anni successivi.
Inclusion/Exclusion Criteria
(Datenquelle: WHO)
Inclusion Criteria MEI-401 Alone:
- Diagnosis of relapsed/refractory CLL and/or relapsed/refractory SLL or FL
- No prior therapy with PI3Kd inhibitors
- No prior therapy with Bruton tyrosine kinase (BTK) inhibitors unless the subject was
intolerant of BTK therapy or subject had disease progression
- Subjects with CLL/SLL must have prior treatment with BTK inhibitor and must have had
progression or recurrence while on treatment of within 12 mos from BTK treatment
- Subject must have failed at least 1 prior systemic therapy
- QT-interval corrected according to Fridericia's formula (QTcF) = 450 milliseconds (ms)
- Left ventricular ejection fraction > 50%
- For subjects, except those with CLL, must have at least one bi-dimensionally
measurable nodal lesion >1.5 cm, as defined by Lugano Classification
- Willingness to participate in collection of pharmacokinetic samples
- A negative serum pregnancy test within 14 days of study Day 0, for females of
childbearing potential
Inclusion Criteria ME-401 in Combination with Rituximab
- Diagnosis of relapsed/refractory CLL SLL or FL, MZL, DLBCL and high-grade B-cell
lymphoma. Subjects must meet the following criteria for relapsed or refractory
disease:
- No prior therapy with PI3Kd inhibitors
- No prior therapy with Bruton tyrosine kinase (BTK) inhibitors unless the subject was
intolerant of BTK therapy or subject had disease progression
- Subjects with CLL, SLL, FL, and MZL must have a failure of at least 1 prior systemic
therapy and be considered by the investigator a candidate for therapy with a
rituximab-based regimen; subjects with DLBCL and high-grade B-cell lymphoma must have
a failure of at least 2 prior therapies.
- QT-interval corrected according to Fridericia's formula (QTcF) =450 milliseconds (ms)
- Left ventricular ejection fraction > 50%
- For subjects, except those with CLL, must have at least one bi-dimensionally
measurable nodal lesion >1.5 cm, as defined by Lugano Classification
- Willingness to participate in collection of pharmacokinetic samples
- A negative serum pregnancy test within 14 days of study Day 0 for females of
childbearing potential
Inclusion Criteria ME-401 in Combination with Zanubrutinib
- Diagnosis of relapsed/refractory CLL or histologically-confirmed relapsed/refractory
SLL or FL, MZL, MCL, DLBCL NOS (germinal center B-cell type or activated B-cell type)
- No prior therapy with PI3Kd inhibitors
- No prior therapy with BTK inhibitors
- Subjects with CLL, SLL, FL, MCL, and MZL must have a failure of at least 1 prior
systemic therapy, require treatment in the opinion of the investigator, and be
considered by the investigator a candidate for therapy subjects with DLBCL and
high-grade B-cell lymphoma must have a failure of at least 2 prior therapies
- For subjects with SLL, FL, MZL, MCL, DLBCL: At least one bi dimensionally measurable
nodal lesion > 1.5 cm in its longest diameter by CT scan or MRI
- QT-interval corrected according to Fridericia's formula (QTcF) = 450 milliseconds
(msec)
- Left ventricular ejection fraction > 50% as measured by echocardiogram or multigated
acquisition (MUGA) scan
- Willingness to participate in collection of pharmacokinetic samples
- For females of childbearing potential, a negative serum pregnancy test within 14 days
of study Day 0
Exclusion Criteria:
- Known histological transformation from CLL to an aggressive lymphoma
- Uncontrolled autoimmune hemolytic anemia or immune thrombocytopenia
- Subjects who have tested positive for hepatitis B surface antigen and/or hepatitis B
core antibody
- Positive for hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV)
antibody
- Ongoing drug-induced pneumonitis
- History of clinically significant cardiovascular abnormalities
- History of severe bleeding disorders (ME-401 plus zanubrutinib arm only)
- Known central nervous system (CNS) hemorrhage or stroke within 6 months prior to start
of study drugs (ME-401 plus zanubrutinib arm only)
-
Weitere Informationen zur Studie
Datum der Studienregistrierung
12.09.2016
Einschluss der ersten teilnehmenden Person
01.10.2016
Rekrutierungsstatus
Active, not recruiting
Wissenschaftlicher Titel
(Datenquelle: WHO)
A Three-Arm Study of ME-401 Monotherapy in Subjects With Relapsed/Refractory CLL, SLL, or FL, of ME-401 in Combination With Rituximab in Subjects With Relapsed/Refractory CLL/SLL or B-cell NHL, and of ME-401 in Combination With Zanubrutinib in Subjects With Relapsed/Refractory CLL/SLL or B-cell NHL
Studientyp
(Datenquelle: WHO)
Interventional
Design der Studie
(Datenquelle: WHO)
Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
Phase
(Datenquelle: WHO)
Phase 1
Primäre Endpunkte
(Datenquelle: WHO)
Minimum Biologically Effective Dose (mBED) of ME-401 alone;Maximally Tolerated Dose (MTD) of ME-401 alone;Dose Limiting Toxicities (DLTs) of ME-401 alone;Evaluate the safety and tolerability of ME-401 plus rituximab;Determine the MTD of ME-401 plus zanubrutinib;Determine the DLTs of ME-401 plus zanubrutinib;Evaluate the safety and tolerability of ME-401 plus zanubrutini
Sekundäre Endpunkte
(Datenquelle: WHO)
Safety profile of ME-401 alone;Efficacy of ME-401 alone as assessed by (OR);Evaluate the (AUC) PK of ME-401 alone;Evaluate the PK (Cmax) of ME-401 alone;Efficacy of ME-401 with rituximab;Evaluate the PK (AUC) of ME-401 with rituximab;Evaluate the PK (Cmax) of ME-401 with rituximab;Efficacy of ME-401 with zanubrutinib;Evaluate the PK (AUC) of ME-401 in combination with zanubrutinib;Evaluate the PK (Cmax) of ME-401 in combination with zanubrutini
Kontakt für Auskünfte
(Datenquelle: WHO)
Please refer to primary and secondary sponsors
Ergebnisse der Studie
(Datenquelle: WHO)
Zusammenfassung der Ergebnisse
noch keine Angaben verfügbar
Link zu den Ergebnissen im Primärregister
noch keine Angaben verfügbar
Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
noch keine Angaben verfügbar
Studiendurchführungsorte
Durchführungsorte in der Schweiz
(Datenquelle: BASEC)
Bellinzona
Durchführungsländer
(Datenquelle: WHO)
Switzerland, United States
Kontakt für weitere Auskünfte zur Studie
Angaben zur Kontaktperson in der Schweiz
(Datenquelle: BASEC)
Katrin Canbulat
+41 79 152 86 26
Katrin.Canbulat@caidya.com
Kontakt für allgemeine Auskünfte
(Datenquelle: WHO)
Lisa McColley
402-238-2615
lmccolley@clinipace.com;TaussigResearch@ccf.org
Kontakt für wissenschaftliche Auskünfte
(Datenquelle: WHO)
Lisa McColley
402-238-2615
lmccolley@clinipace.com;TaussigResearch@ccf.org
Bewilligung durch Ethikkommission (Datenquelle: BASEC)
Name der bewilligenden Ethikkommission (bei multizentrischen Studien nur die Leitkommission)
Comitato etico cantonale Ticino
Datum der Bewilligung durch die Ethikkommission
18.07.2017
Weitere Studienidentifikationsnummern
Studienidentifikationsnummer der Ethikkommission (BASEC-ID)
(Datenquelle: BASEC)
2017-00651
Secondary ID (Datenquelle: WHO)
ME-401-002
Zurück zur Übersicht