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SNCTP000002290 | NCT02914938 | BASEC2017-00651

Studio internazionale volto a esaminare la sicurezza, la tollerabilità e l’efficacia di un farmaco sperimentale denominato ME-401 come potenziale trattamento per i pazienti affetti da leucemia linfatica cronica (CLL), linfoma linfocitico a piccole cellule (SLL) o linfoma follicolare (FL) recidivante/refrattario.

Data source: BASEC (Imported from 14.04.2021), WHO (Imported from 11.04.2021)
Changed: 08.04.2021
Disease category: Leukemia, Non-Hodgkin Lymphoma

Brief description of trial (Data source: 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.

Health conditions investigated (Data source: 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 (Data source: 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)

Rare disease (Data source: BASEC)

No

Intervention investigated (e.g. drug, therapy or campaign) (Data source: 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 (Data source: WHO)

Drug: ME-401;Drug: Rituximab;Drug: Zanubrutinib

Criteria for participation in trial (Data source: 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.

Exclusion criteria (Data source: 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 (Data source: 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)

Further information on the trial in WHO primary registry

https://clinicaltrials.gov/show/NCT02914938

Further information on the trial from WHO database (ICTRP)

http://apps.who.int/trialsearch/Trial2.aspx?TrialID=NCT02914938

Further information on trial

Date trial registered

12.09.2016

Incorporation of the first participant

01.10.2016

Recruitment status

Recruiting

Academic title (Data source: 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

Type of trial (Data source: WHO)

Interventional

Design of the trial (Data source: WHO)

Allocation: Non-Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).

Phase (Data source: WHO)

Phase 1

Primary end point (Data source: 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;Evaluate the safety and tolerability of ME-401 plus zanubrutinib;Determine the DLTs of ME-401 plus zanubrutinib;Determine the MTD of ME-401 plus zanubrutinib

Secundary end point (Data source: 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 zanubrutinib

Contact information (Data source: WHO)

Please refer to primary and secondary sponsors

Trial results (Data source: WHO)

Results summary

no information available yet

Link to the results in the primary register

no information available yet

Information on the availability of individual participant data

no information available yet

Trial sites

Trial sites in Switzerland (Data source: BASEC)

Bellinzona

Countries (Data source: WHO)

Switzerland, United States

Contact for further information on the trial

Details of contact in Switzerland (Data source: BASEC)

Martin Juenger
+41 44 908 66 87
mjuenger@clinipace.com

Contact for general information (Data source: WHO)

Lisa McColley
402-238-2615
lmccolley@clinipace.com;TaussigResearch@ccf.org

Contact for scientific information (Data source: WHO)

Lisa McColley
402-238-2615
lmccolley@clinipace.com;TaussigResearch@ccf.org

Principal Sponsor/Investigator

Principal sponsor (Data source: WHO)

MEI Pharma, Inc.

Authorisation by the ethics committee (Data source: BASEC)

Name of the authorising ethics committee (for multicentre studies only the lead committee)

Comitato etico cantonale Ticino

Date of authorisation by the ethics committee

18.07.2017

Further trial identification numbers

Trial identification number of the ethics committee (BASEC-ID) (Data source: BASEC)

2017-00651

Secondary ID (Data source: WHO)

ME-401-002