Phase 3 Study of Zandelisib (ME-401) in Combination With Rituximab in Patients With iNHL - (COASTAL)

Non Hodgkin Lymphoma Clinical Trial

Official title:

A Phase 3, Randomized, Open-Label, Controlled, Multicenter Study of Zandelisib (ME- 401) in Combination With Rituximab Versus Standard Immunochemotherapy in Patients With Relapsed Indolent Non Hodgkin's Lymphoma (iNHL) - The COASTAL Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04745832
• Other study ID #: ME-401-004
• Secondary ID: 2020-004199-16
• Status: Terminated
• Phase: Phase 3
• Start date: August 13, 2021
• Est. completion date: March 20, 2023

Study information

• Verified date: December 2022
• Source: MEI Pharma, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a Phase 3 study of the PI3Kδ inhibitor Zandelisib (ME-401) in combination with rituximab, in comparison to standard immunochemotherapy (Rituximab-Bendamustine or Rituximab-CHOP) in subjects with relapsed or refractory FL and MZL.

Description:

This is an open label, randomized, two-arm Phase 3 study in subjects with relapsed or refractory FL and MZL to evaluate efficacy and safety of zandelisib in combination with rituximab in comparison to standard immunochemotherapy (Rituximab-Bendamustine or Rituximab-CHOP). Subjects must have relapsed after at least one previous line of systemic immunochemotherapy. Previous treatments must have included an anti-CD20 monoclonal antibody (mAb) with chemotherapy such as Bendamustine (B), CHOP, CVP, FND, or similar regimens, or an anti-CD20 mAb with Lenalidomide (L). Approximately 534 randomized subjects will be enrolled in this study.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 82
• Est. completion date: March 20, 2023
• Est. primary completion date: March 20, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Male or female subjects =18 years of age, =19 years in Korea, or =20 years for subjects in Japan and Taiwan
• Histologically confirmed diagnosis of CD20 positive iNHL with histological subtype

limited to:

1. FL Gr 1, Gr 2, or Gr 3a

2. MZL (splenic, nodal, or extra-nodal)

• Subjects with relapsed or refractory disease who received =1 prior lines of therapy
• Subjects must have at least one bi-dimensionally measurable lesion >1.5 cm
• Adequate hematologic parameters at screening unless abnormal values are due to disease
• Adequate renal and hepatic function
• Adequate cardiac function based on ECG and LVEF assessments

Exclusion Criteria:

• Histologically confirmed diagnosis of FL Gr 3b or transformed disease
• Prior therapy with PI3K inhibitors
• Ongoing or history of drug-induced pneumonitis
• Known lymphomatous involvement of the central nervous system
• Tested positive for or active viral infection with hepatitis B or C virus
• Tested positive or active infection with human immunodeficiency virus
• Tested positive, or active infection with human T-cell leukemia virus type 1
• Any uncontrolled clinically significant illness
• History of clinically significant cardiovascular abnormalities such as congestive heart failure
• History of clinically significant gastrointestinal (GI) conditions
• Females who are pregnant

Related Conditions & MeSH terms

• Follicular Lymphoma (FL)
• Lymphoma
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Non-Hodgkin
• Marginal Zone Lymphoma
• Non Hodgkin Lymphoma

Intervention

Drug:
• Zandelisib
Zandelisib 60 mg capsules taken daily for two cycles followed by intermittent schedule starting at Cycle 3
• Rituximab
Rituximab IV 375 mg/m2 for 6 cycles
• Bendamustine
Bendamustine IV 90 mg/m2 on Days 1 and 2 for 6 cycles
• CHOP
Cyclophosphamide, Vindcristine IV, and Prednisone daily orally

Locations

Country	Name	City	State
Australia	Canberra Hospital	Garran
Australia	The Perth Blood Institute (PBI)	West Perth
Australia	Westmead Hospital	Westmead
Belgium	AZ Sint-Jan Burgge-Oostende AV	Brugge
Belgium	UZ Brussel	Brussel
Belgium	Universitair Ziekenhuis Antwerpen	Edegem
Belgium	Center Hospitalier de Jolimont	Haine-Saint-Paul
Belgium	UZ Leuven Campus Gasthuisberg	Leuven
Canada	McGill University Health Centre	Québec
Canada	Eastern Regional Health Authority	Saint John's	Newfoundland and Labrador
Canada	Centre intégré universitaire de santé et de services sociaux de l'Estrie	Sherbrooke	Quebec
France	CHU Estaing. Service d'hématologie clinique et de thérapie cellulaire adulte,	Clermont-Ferrand
France	Centre Hospitalier De Dunkerque - Service d'hématologie	Le Mans
France	Centre Hospitalier du Mans	Le Mans
France	Centre Leon Berard	Lyon
France	Hôpital Saint-Louis	Paris
France	CHU de Bordeaux - Maladies Du Sang, Centre François Magendie	Pessac
France	Centre Henri Becquerel, Service d'Hematologie	Rouen
France	CHU de Tours, Hôpital Bretonneau Centre	Tours Cedex 1
France	Institut De Cancerologie Gustave Roussy	Villejuif
Georgia	J.S.C. K. Eristavi National Center of Experimental and Clinic	Tbilisi
Georgia	LTD "Medinvest" Institute of Hematology and Transfusiology	Tbilisi
Georgia	LTD Israeli-Georgian Medical Research Clinic "Helsicore"	Tbilisi
Georgia	M. Zodelava Hematology Center	Tbilisi
Greece	General Hospital of Athens "Laiko", Department of Haematology and Bone Marrow Transplantation	Athens
Greece	University General Hospital of Ioannina, Department of Haematology	Ioánnina
Greece	University General Hospital of Patras "Panagia H. Voitheia"	Patras
Greece	General Hospital of Thessaloniki "G. Papanikolaou"	Thessaloníki
Hungary	Országos Onkológiai Intézet Gyógyszerterápiás Központ Hematológia és Lymphoma Osztály	Budapest
Hungary	Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Klinika	Debrecen
Hungary	Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz,	Nyiregyhaza
Italy	SOC Oncologia Medica e dei Tumori Immunocorrelati	Aviano
Italy	UO di Ematologia "L.e A.Seragnoli" Policlinico Sant'Orsola Malpighi	Bologna
Italy	U.O. Ematologia, Azienda Ospedaliera S. Croce e Carle	Cuneo
Italy	U.O. Ematologia - Azienda Ospedaliero-Universitaria Careggi	Firenze
Italy	U.O. Clinica Ematologica	Genova
Italy	SC Oncologia Medica	Meldola
Italy	UOC Ematologia, Presidio Ospedaliero Papardo	Messina
Italy	UO Ematologia 1 Azienda ULSS 3 Serenissima, Distertto del veneziano - Ospedale dell'Angelo di Mestre	Mestre
Italy	Dipartimento di Oncoematologia, Unità Linfomi, Ospedale	Milano
Italy	Divisione Oncoematologia, Istituto Europeo di Oncologia	Milano
Italy	Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano	Milano
Italy	Azienda Ospedaliera Ospedali Riuniti Via Sofia	Palermo
Italy	UO Ematologia, Ospedale Civile S.Maria delle Croci	Ravenna
Italy	UO Ematologia, Ospedale Infermi di Rimini AUSL Romagna	Rimini
Italy	Istituti Fisioterapici Ospitalieri	Roma
Italy	S.C. Oncoematologia Azienda Ospedaliera Santa Maria	Terni
Japan	Anjo Kosei Hospital	Aichi
Japan	Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital	Aichi
Japan	Aomori Prefectural Central Hospital	Aomori
Japan	Chiba Cancer Center	Chiba
Japan	Kyushu University Hospital	Fukuoka
Japan	Chugoku Central Hospital	Hiroshima
Japan	Hokkaido University Hospital	Hokkaido
Japan	University Hospital Kyoto Prefectural University of Medicine	Kamigyo-ku	Kyoto
Japan	Kobe City Medical Center General Hospital	Kobe	Hyogo
Japan	National Hospital Organization Kumamoto Medical Center	Kumamoto
Japan	Kyoto University Hospital	Kyoto
Japan	Gunma University Hospital	Maebashi	Gunma
Japan	National Hospital Organization Shikoku Cancer Center	Matsuyama-Shi	Ehime
Japan	National Hospital Organization Kyushu Cancer Center	Minami	Fukuoka
Japan	National University Corporation Tohoku University Hospital	Miyagi
Japan	Aichi Cancer Center Hospital	Nagoya
Japan	National Hospital Organization Nagoya Medical Center	Naka-ku	Aichi
Japan	Okayama University Hospital	Okayama
Japan	Osaka International Cancer Institute	Osaka
Japan	Osaka University Hospital	Osaka
Japan	Kindai University Hospital	Osakasayama-shi	Osaka
Japan	Kagoshima University Hospital	Sakuragaoka	Kagoshima-Shi, Kagoshima
Japan	Keio University Hospital	Tokyo
Japan	The Cancer Institute Hospital of Japanese Foundation For Cancer Research	Tokyo
Japan	Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital	Tokyo
Korea, Republic of	Dong-A university Hospital	Busan
Korea, Republic of	Inje University Busan Paik Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollyang
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Ewka Womans University Mokdong Hospital	Seoul
Korea, Republic of	Korea University Anam Hospital	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Korea, Republic of	The Catholic University of Korea	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan
Netherlands	Albert Schweizer Ziekenhuis, Hematology Department	Dordrecht
Netherlands	Spaarne Gasthuis, Oncology Department	Hoofddorp
New Zealand	Canterbury District Health Board, Haematology Department	Christchurch
New Zealand	Dunedin Hospital, Southern Blood and Cancer Service	Dunedin
Poland	Klinika Hematologii, Szpital Uniwersytecki	Bydgoszcz
Poland	Pratia MCM Krakow	Kraków
Poland	ARS Medical - Szpital, Oddzial hematologiczny	Pila
Poland	Centrum Medyczne Pratia Poznan	Skorzewo
Serbia	Clinical Hospital Center "Zemun", Clinic for Internal Medicine, Department for Hematology	Belgrade
Serbia	University Clinical Center of Serbia, Clinic for Hematology	Belgrade
Serbia	Zvezdara University Medical Center, Clinical department for Hematology and Oncology	Belgrade
Serbia	Oncology Institute of Vojvodina, Clinic for Internal Oncology	Kamenica
Serbia	University Clinical Center Kragujevac, Clinic for Hematology	Kragujevac
Serbia	Clinical Center of Vojvodina, Clinic for Hematology	Novi Sad
Spain	Hospital Universitario Quironsalud	Alcorcón	Madrid
Spain	Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Oncology	Barcelona
Spain	Hospital Universitario Mútua Terrassa	Barcelona
Spain	Institut Catalá d'Oncologia, Hospital Duran i Reynals	Barcelona
Spain	Hospital Universitario Ramón y Cajal	Madrid
Spain	Complejo Hospitalario de Navarra	Navarro
Spain	Hospital Universitario de Canarias	Santa Cruz De Tenerife
Spain	Hospital Universitario Virgen Macarena	Sevilla
Spain	Hospital Universitario Miguel Servet	Zaragoza
Taiwan	China Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	Chi Mei Hospital	Tainan City
Turkey	Gazi University Health Research and Application Hospital, Hematology Department	Ankara
Turkey	Istanbul University Istanbul Medical Faculty, Hematology Department	Istanbul
Turkey	Erciyes University Medical Faculty, Department of Hematology	Kayseri
Turkey	Ondokuz Mayis University Medical Faculty, Hematology Department	Samsun
Turkey	Namik Kemal University Hospital	Tekirdag
Turkey	Karadeniz Technical University Medical Faculty Department of Hematology	Trabzon
United Kingdom	North Wales Cancer Treatment Centre	Bodelwyddan	Denbighshire
United Kingdom	Royal Cornwall Hospital	Cornwell
United Kingdom	Department of Haematology St. George's University of London	London
United Kingdom	Imperial College Healthcare NHS Trust Hammersmith Hospital	London
United Kingdom	The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United Kingdom	Genesis Care Oxford	Oxford
United Kingdom	University Hospitals Plymouth NHS Trust, Derriford Hopital	Plymouth
United Kingdom	The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital	Surrey Quays
United States	Alpha Research Institute, LLC	Baytown	Texas
United States	MetroHealth Medical Center	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Revive Research Institute	Farmington Hills	Michigan
United States	Orange Coast Memorial Medical Center	Fountain Valley	California
United States	Valley Cancer Associates	Harlingen	Texas
United States	BRCR Medical Center Inc	Hollywood	Florida
United States	Long Beach Memorial Medical Center	Long Beach	California
United States	Inspira Medical Center Mullica Hill	Mullica Hill	New Jersey
United States	Community Cancer Trials of Utah	Ogden	Utah
United States	The Oncology Institute of Hope and Innovation	Riverside	California
United States	Mercy Clinic Cancer & Hematology - Chub O'Reilly Cancer Center	Springfield	Missouri
United States	Revive Research Institute	Sterling Heights	Michigan
United States	The Oncology Institute of Hope and Innovation	Tucson	Arizona

Sponsors (2)

Lead Sponsor	Collaborator
MEI Pharma, Inc.	Kyowa Kirin, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Georgia,  Greece,  Hungary,  Italy,  Japan,  Korea, Republic of,  Netherlands,  New Zealand,  Poland,  Serbia,  Spain,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival	PFS is defined as the time from randomization date until the date of disease progression, or death from any cause	1 year 7 months
Secondary	Overall Response Rate (ORR)	ORR is defined as the proportion of subjects who have a best overall response of CR or PR according to the Lugano Classification over the entire duration of the study, including the efficacy follow-up period.	1 year 7 months
Secondary	Complete Response Rate (CRR)	CRR is defined as the proportion of subjects who have a best overall response of CR during the study (i.e., up to time of analysis of PFS).	1 year 7 months
Secondary	Overall Survival	OS is defined as the time (in days) from randomization until death from any cause. For subjects alive at the time of analysis, they will be censored at the last documented alive date.	1 year 7 months
Secondary	Number of Treatment Emergent AEs (Zandelisib When Combined With Rituximab)	Measured by the number of Treatment Emergent AEs	1 year 7 months
Secondary	Number of SAEs (Zandelisib When Combined With Rituximab)	Measured by the number of SAEs	1 year 7 months
Secondary	Number of Lab Abnormalities (Zandelisib When Combined With Rituximab)	Measured by the number of laboratory abnormalities	1 year 7 months