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

NCT ID: NCT04745832

Last Updated: 2024-11-04

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 82 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-13
• Study Completion Date: 2023-03-20

Brief 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.

Detailed 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.

Conditions

Follicular Lymphoma (FL); Non Hodgkin Lymphoma; Marginal Zone Lymphoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rituximab plus Zandelisib

Rituximab plus Zandelisib for 6 cycles followed by Zandelisib for 20 cycles

Group Type: EXPERIMENTAL

Zandelisib

Intervention Type: DRUG

Zandelisib 60 mg capsules taken daily for two cycles followed by intermittent schedule starting at Cycle 3

Rituximab

Intervention Type: DRUG

Rituximab IV 375 mg/m2 for 6 cycles

Rituximab plus chemotherapy

Rituximab and Bendamustine or Rituximab with (CHOP) for 6 cycles

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

Rituximab IV 375 mg/m2 for 6 cycles

Bendamustine

Intervention Type: DRUG

Bendamustine IV 90 mg/m2 on Days 1 and 2 for 6 cycles

CHOP

Intervention Type: DRUG

Cyclophosphamide, Vindcristine IV, and Prednisone daily orally

Interventions

Zandelisib

Zandelisib 60 mg capsules taken daily for two cycles followed by intermittent schedule starting at Cycle 3

Intervention Type: DRUG

Rituximab

Rituximab IV 375 mg/m2 for 6 cycles

Intervention Type: DRUG

Bendamustine

Bendamustine IV 90 mg/m2 on Days 1 and 2 for 6 cycles

Intervention Type: DRUG

CHOP

Cyclophosphamide, Vindcristine IV, and Prednisone daily orally

Intervention Type: DRUG

Other Intervention Names

ME-401; Rituxan; MabThera; Bendeka, Treanda, Belrapzo; cyclophosphamide 750 mg/m2, hydroxydoxorubicin IV 50 mg/m2, vincristine IV 1.4 mg/m2 and prednisone 100 mg daily

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Kyowa Kirin, Inc.

INDUSTRY

Sponsor Role: collaborator

MEI Pharma, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Oncology Institute of Hope and Innovation

Tucson, Arizona, United States

Orange Coast Memorial Medical Center

Fountain Valley, California, United States

Long Beach Memorial Medical Center

Long Beach, California, United States

The Oncology Institute of Hope and Innovation

Riverside, California, United States

BRCR Medical Center Inc

Hollywood, Florida, United States

Henry Ford Hospital

Detroit, Michigan, United States

Revive Research Institute

Farmington Hills, Michigan, United States

Revive Research Institute

Sterling Heights, Michigan, United States

Mercy Clinic Cancer & Hematology - Chub O'Reilly Cancer Center

Springfield, Missouri, United States

Inspira Medical Center Mullica Hill

Mullica Hill, New Jersey, United States

MetroHealth Medical Center

Cleveland, Ohio, United States

Alpha Research Institute, LLC

Baytown, Texas, United States

Valley Cancer Associates

Harlingen, Texas, United States

Community Cancer Trials of Utah

Ogden, Utah, United States

Canberra Hospital

Garran, , Australia

The Perth Blood Institute (PBI)

West Perth, , Australia

Westmead Hospital

Westmead, , Australia

AZ Sint-Jan Burgge-Oostende AV

Bruges, , Belgium

UZ Brussel

Brussels, , Belgium

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Center Hospitalier de Jolimont

Haine-Saint-Paul, , Belgium

UZ Leuven Campus Gasthuisberg

Leuven, , Belgium

Eastern Regional Health Authority

St. John's, Newfoundland and Labrador, Canada

Centre intégré universitaire de santé et de services sociaux de l'Estrie

Sherbrooke, Quebec, Canada

McGill University Health Centre

Québec, , Canada

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, , France

Institut De Cancerologie Gustave Roussy

Villejuif, , France

LTD Israeli-Georgian Medical Research Clinic "Helsicore"

Tbilisi, , Georgia

M. Zodelava Hematology Center

Tbilisi, , Georgia

J.S.C. K. Eristavi National Center of Experimental and Clinic

Tbilisi, , Georgia

LTD "Medinvest" Institute of Hematology and Transfusiology

Tbilisi, , Georgia

General Hospital of Athens "Laiko", Department of Haematology and Bone Marrow Transplantation

Athens, , Greece

University General Hospital of Ioannina, Department of Haematology

Ioannina, , Greece

University General Hospital of Patras "Panagia H. Voitheia"

Pátrai, , Greece

General Hospital of Thessaloniki "G. Papanikolaou"

Thessaloniki, , Greece

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,

Nyíregyháza, , Hungary

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

Florence, , 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

Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano

Milan, , Italy

Dipartimento di Oncoematologia, Unità Linfomi, Ospedale

Milan, , Italy

Divisione Oncoematologia, Istituto Europeo di Oncologia

Milan, , 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, , Italy

National Hospital Organization Nagoya Medical Center

Naka-ku, Aichi-ken, Japan

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, Japan

National Hospital Organization Kyushu Cancer Center

Minami, Fukuoka, Japan

Gunma University Hospital

Maebashi, Gunma, Japan

Kobe City Medical Center General Hospital

Kobe, Hyōgo, Japan

Kagoshima University Hospital

Sakuragaoka, Kagoshima-Shi, Kagoshima, Japan

University Hospital Kyoto Prefectural University of Medicine

Kamigyō-ku, Kyoto, Japan

Kindai University Hospital

Osakasayama-shi, Osaka, 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

National Hospital Organization Kumamoto Medical Center

Kumamoto, , Japan

Kyoto University Hospital

Kyoto, , Japan

National University Corporation Tohoku University Hospital

Miyagi, , Japan

Aichi Cancer Center Hospital

Nagoya, , Japan

Okayama University Hospital

Okayama, , Japan

Osaka International Cancer Institute

Osaka, , Japan

Osaka University Hospital

Osaka, , Japan

Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital

Tokyo, , Japan

The Cancer Institute Hospital of Japanese Foundation For Cancer Research

Tokyo, , Japan

Keio University Hospital

Tokyo, , Japan

Albert Schweizer Ziekenhuis, Hematology Department

Dordrecht, , Netherlands

Spaarne Gasthuis, Oncology Department

Hoofddorp, , Netherlands

Canterbury District Health Board, Haematology Department

Christchurch, , New Zealand

Dunedin Hospital, Southern Blood and Cancer Service

Dunedin, , New Zealand

Klinika Hematologii, Szpital Uniwersytecki

Bydgoszcz, , Poland

Pratia MCM Krakow

Krakow, , Poland

ARS Medical - Szpital, Oddzial hematologiczny

Piła, , Poland

Centrum Medyczne Pratia Poznan

Skorzewo, , Poland

University Clinical Center of Serbia, Clinic for Hematology

Belgrade, , Serbia

Zvezdara University Medical Center, Clinical department for Hematology and Oncology

Belgrade, , Serbia

Clinical Hospital Center "Zemun", Clinic for Internal Medicine, Department for Hematology

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, , Serbia

Inje University Busan Paik Hospital

Busan, , South Korea

Dong-A university Hospital

Busan, , South Korea

Pusan National University Hospital

Busan, , South Korea

Kyungpook National University Hospital

Daegu, , South Korea

Chonnam National University Hwasun Hospital

Jeollyang, , South Korea

Korea University Anam Hospital

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Samsung Medical Center

Seoul, , South Korea

The Catholic University of Korea

Seoul, , South Korea

Ewka Womans University Mokdong Hospital

Seoul, , South Korea

Ulsan University Hospital

Ulsan, , South Korea

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

Seville, , Spain

Hospital Universitario Miguel Servet

Zaragoza, , Spain

China Medical University Hospital

Taichung, , Taiwan

Taichung Veterans General Hospital

Taichung, , Taiwan

National Cheng Kung University Hospital

Tainan City, , Taiwan

Chi Mei Hospital

Tainan City, , Taiwan

Gazi University Health Research and Application Hospital, Hematology Department

Ankara, , Turkey (Türkiye)

Istanbul University Istanbul Medical Faculty, Hematology Department

Istanbul, , Turkey (Türkiye)

Erciyes University Medical Faculty, Department of Hematology

Kayseri, , Turkey (Türkiye)

Ondokuz Mayis University Medical Faculty, Hematology Department

Samsun, , Turkey (Türkiye)

Namik Kemal University Hospital

Tekirdağ, , Turkey (Türkiye)

Karadeniz Technical University Medical Faculty Department of Hematology

Trabzon, , Turkey (Türkiye)

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

The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital

London, , United Kingdom

Imperial College Healthcare NHS Trust Hammersmith 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 Kingdom

Countries

United States; Australia; Belgium; Canada; France; Georgia; Greece; Hungary; Italy; Japan; Netherlands; New Zealand; Poland; Serbia; South Korea; Spain; Taiwan; Turkey (Türkiye); United Kingdom

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2020-004199-16

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ME-401-004

Identifier Type: -

Identifier Source: org_study_id