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

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

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.

Study Overview

• Status: Terminated
• Conditions: Marginal Zone Lymphoma; Non Hodgkin Lymphoma; Follicular Lymphoma (FL)
• Intervention / Treatment: Drug: Zandelisib; Drug: Rituximab; Drug: Bendamustine; Drug: CHOP

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.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Garran, Australia, 2605
    • Canberra Hospital
  • West Perth, Australia, 6005
    • The Perth Blood Institute (PBI)
  • Westmead, Australia, 2145
    • Westmead Hospital
• Belgium
  • Brugge, Belgium, 8000
    • AZ Sint-Jan Burgge-Oostende AV
  • Brussel, Belgium, 1090
    • UZ Brussel
  • Edegem, Belgium, 655, 2650
    • Universitair Ziekenhuis Antwerpen
  • Haine-Saint-Paul, Belgium, 7100
    • Center Hospitalier de Jolimont
  • Leuven, Belgium
    • Uz Leuven Campus Gasthuisberg
• Canada
  • Québec, Canada, H4A 3J1
    • McGill University Health Centre
  • Newfoundland and Labrador
    • Saint John's, Newfoundland and Labrador, Canada, A1B3V6
      • Eastern Regional Health Authority
  • Quebec
    • Sherbrooke, Quebec, Canada, JIH5N4
      • Centre integre universitaire de sante et de services sociaux de l'Estrie
• France
  • Clermont-Ferrand, France, 63003
    • CHU Estaing. Service d'hématologie clinique et de thérapie cellulaire adulte,
  • Le Mans, France, 72000
    • Centre Hospitalier du Mans
  • Le Mans, France, 72000
    • Centre Hospitalier De Dunkerque - Service d'hématologie
  • Lyon, France, 69373
    • Centre Leon Berard
  • Paris, France, 75010
    • Hopital Saint-Louis
  • Pessac, France, 33600
    • CHU de Bordeaux - Maladies Du Sang, Centre François Magendie
  • Rouen, France, 76038
    • Centre Henri Becquerel, Service d'Hematologie
  • Tours Cedex 1, France, 37044
    • CHU de Tours, Hôpital Bretonneau Centre
  • Villejuif, France, 94805
    • Institut de Cancérologie Gustave Roussy
• Georgia
  • Tbilisi, Georgia, 0112
    • LTD Israeli-Georgian Medical Research Clinic "Helsicore"
  • Tbilisi, Georgia, 0112
    • M. Zodelava Hematology Center
  • Tbilisi, Georgia, 0159
    • J.S.C. K. Eristavi National Center of Experimental and Clinic
  • Tbilisi, Georgia, 0186
    • LTD "Medinvest" Institute of Hematology and Transfusiology
• Greece
  • Athens, Greece, 11527
    • General Hospital of Athens "Laiko", Department of Haematology and Bone Marrow Transplantation
  • Ioánnina, Greece, 455 00
    • University General Hospital of Ioannina, Department of Haematology
  • Patras, Greece, 26504
    • University General Hospital of Patras "Panagia H. Voitheia"
  • Thessaloníki, Greece, 57010
    • General Hospital of Thessaloniki "G. Papanikolaou"
• Hungary
  • Budapest, Hungary, H-1122
    • Országos Onkológiai Intézet Gyógyszerterápiás Központ Hematológia és Lymphoma Osztály
  • Debrecen, Hungary, H-4032
    • Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Klinika
  • Nyiregyhaza, Hungary, H-4400
    • Szabolcs-Szatmár-Bereg Megyei Kórházak és Egyetemi Oktatókórház,
• Italy
  • Aviano, Italy, 33081
    • SOC Oncologia Medica e dei Tumori Immunocorrelati
  • Bologna, Italy, 40138
    • UO di Ematologia "L.e A.Seragnoli" Policlinico Sant'Orsola Malpighi
  • Cuneo, Italy, 12100
    • U.O. Ematologia, Azienda Ospedaliera S. Croce e Carle
  • Firenze, Italy, 50134
    • U.O. Ematologia - Azienda Ospedaliero-Universitaria Careggi
  • Genova, Italy, 16132
    • U.O. Clinica Ematologica
  • Meldola, Italy, 47014
    • SC Oncologia Medica
  • Messina, Italy, 98158
    • UOC Ematologia, Presidio Ospedaliero Papardo
  • Mestre, Italy, 30174
    • UO Ematologia 1 Azienda ULSS 3 Serenissima, Distertto del veneziano - Ospedale dell'Angelo di Mestre
  • Milano, Italy, 20122
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano
  • Milano, Italy, 20132
    • Dipartimento di Oncoematologia, Unità Linfomi, Ospedale
  • Milano, Italy, 20141
    • Divisione Oncoematologia, Istituto Europeo di Oncologia
  • Palermo, Italy, 90146
    • Azienda Ospedaliera Ospedali Riuniti Via Sofia
  • Ravenna, Italy, 48121
    • UO Ematologia, Ospedale Civile S.Maria delle Croci
  • Rimini, Italy, 47923
    • UO Ematologia, Ospedale Infermi di Rimini AUSL Romagna
  • Roma, Italy, 00144
    • Istituti Fisioterapici Ospitalieri
  • Terni, Italy, 05110
    • S.C. Oncoematologia Azienda Ospedaliera Santa Maria
• Japan
  • Aichi, Japan, 446-8602
    • Anjo Kosei Hospital
  • Aichi, Japan, 466-8650
    • Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital
  • Aomori, Japan, 030-8553
    • Aomori Prefectural Central Hospital
  • Chiba, Japan, 260-8717
    • Chiba Cancer Center
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Hiroshima, Japan, 720-0001
    • Chugoku Central Hospital
  • Hokkaido, Japan, 060-8648
    • Hokkaido University Hospital
  • Kumamoto, Japan, 860-0008
    • National Hospital Organization Kumamoto Medical Center
  • Kyoto, Japan, 606-8507
    • Kyoto University Hospital
  • Miyagi, Japan, 980-8574
    • National University Corporation Tohoku University Hospital
  • Nagoya, Japan, 464-8681
    • Aichi Cancer Center Hospital
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Osaka, Japan, 565-0871
    • Osaka University Hospital
  • Osaka, Japan, 541-8567
    • Osaka International Cancer Institute
  • Tokyo, Japan, 160-8582
    • Keio University Hospital
  • Tokyo, Japan, 135-8550
    • The Cancer Institute Hospital of Japanese Foundation for Cancer Research
  • Tokyo, Japan, 113-8677
    • Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital
  • Aichi
    • Naka-ku, Aichi, Japan, 460-0001
      • National Hospital Organization Nagoya Medical Center
  • Ehime
    • Matsuyama-Shi, Ehime, Japan, 791-0280
      • National Hospital Organization Shikoku Cancer Center
  • Fukuoka
    • Minami, Fukuoka, Japan, 811-1395
      • National Hospital Organization Kyushu Cancer Center
  • Gunma
    • Maebashi, Gunma, Japan, 371-8511
      • Gunma University Hospital
  • Hyogo
    • Kobe, Hyogo, Japan, 650-0047
      • Kobe City Medical Center General Hospital
  • Kagoshima-Shi, Kagoshima
    • Sakuragaoka, Kagoshima-Shi, Kagoshima, Japan, 890-8520
      • Kagoshima University Hospital
  • Kyoto
    • Kamigyo-ku, Kyoto, Japan, 602-8566
      • University Hospital Kyoto Prefectural University of Medicine
  • Osaka
    • Osakasayama-shi, Osaka, Japan, 589-8511
      • Kindai University Hospital
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Pusan National University Hospital
  • Busan, Korea, Republic of, 49201
    • Dong-A University Hospital
  • Busan, Korea, Republic of, 47392
    • Inje University Busan Paik Hospital
  • Daegu, Korea, Republic of, 41944
    • Kyungpook National University Hospital
  • Jeollyang, Korea, Republic of, 58128
    • Chonnam National University Hwasun Hospital
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 02841
    • Korea University Anam Hospital
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
  • Seoul, Korea, Republic of, 06591
    • The Catholic University of Korea
  • Seoul, Korea, Republic of, 07985
    • Ewka Womans University Mokdong Hospital
  • Ulsan, Korea, Republic of, 44033
    • Ulsan University Hospital
• Netherlands
  • Dordrecht, Netherlands, 3318
    • Albert Schweizer Ziekenhuis, Hematology Department
  • Hoofddorp, Netherlands, 2134
    • Spaarne Gasthuis, Oncology Department
• New Zealand
  • Christchurch, New Zealand, 8011
    • Canterbury District Health Board, Haematology Department
  • Dunedin, New Zealand, 9016
    • Dunedin Hospital, Southern Blood and Cancer Service
• Poland
  • Bydgoszcz, Poland, 85-168
    • Klinika Hematologii, Szpital Uniwersytecki
  • Kraków, Poland, 30-510
    • PRATIA MCM Kraków
  • Piła, Poland, 64-920
    • ARS Medical - Szpital, Oddzial hematologiczny
  • Skorzewo, Poland, 60-185
    • Centrum Medyczne Pratia Poznań
• Serbia
  • Belgrade, Serbia, 11000
    • University Clinical Center of Serbia, Clinic for Hematology
  • Belgrade, Serbia, 11000
    • Zvezdara University Medical Center, Clinical department for Hematology and Oncology
  • Belgrade, Serbia, 11080
    • Clinical Hospital Center "Zemun", Clinic for Internal Medicine, Department for Hematology
  • Kamenica, Serbia, 21204
    • Oncology Institute of Vojvodina, Clinic for Internal Oncology
  • Kragujevac, Serbia, 34000
    • University Clinical Center Kragujevac, Clinic for Hematology
  • Novi Sad, Serbia, 21000
    • Clinical Center of Vojvodina, Clinic for Hematology
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Oncology
  • Barcelona, Spain, 08221
    • Hospital Universitario Mútua Terrassa
  • Barcelona, Spain, 08908
    • Institut Catalá d'Oncologia, Hospital Duran i Reynals
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Navarro, Spain, 31008
    • Complejo Hospitalario de Navarra
  • Santa Cruz De Tenerife, Spain, 38320
    • Hospital Universitario de Canarias
  • Sevilla, Spain, 41009
    • Hospital Universitario Virgen Macarena
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Madrid
    • Alcorcón, Madrid, Spain, 28223
      • Hospital Universitario Quirónsalud
• Taiwan
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Taichung, Taiwan, 404332
    • China Medical University Hospital
  • Tainan, Taiwan, 704
    • National Cheng Kung University Hospital
  • Tainan City, Taiwan, 73657
    • Chi Mei Hospital
• Turkey
  • Ankara, Turkey, 29 06560
    • Gazi University Health Research and Application Hospital, Hematology Department
  • Istanbul, Turkey, 34093
    • Istanbul University Istanbul Medical Faculty, Hematology Department
  • Kayseri, Turkey, 38039
    • Erciyes University Medical Faculty, Department of Hematology
  • Samsun, Turkey, 55200
    • Ondokuz Mayis University Medical Faculty, Hematology Department
  • Tekirdağ, Turkey, 59100
    • Namik Kemal University Hospital
  • Trabzon, Turkey, 61080
    • Karadeniz Technical University Medical Faculty Department of Hematology
• United Kingdom
  • Cornwell, United Kingdom, TR1 3LJ
    • Royal Cornwall Hospital
  • London, United Kingdom, W12 0HS
    • Imperial College Healthcare NHS Trust Hammersmith Hospital
  • London, United Kingdom, SW17 0RE
    • Department of Haematology St. George's University of London
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Oxford, United Kingdom, OX4 6LB
    • Genesis Care Oxford
  • Plymouth, United Kingdom, PL6 8DH
    • University Hospitals Plymouth NHS Trust, Derriford Hopital
  • Surrey Quays, United Kingdom, SM2 5PT
    • The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital
  • Denbighshire
    • Bodelwyddan, Denbighshire, United Kingdom, LL18 5UJ
      • North Wales Cancer Treatment Centre
• United States
  • Arizona
    • Tucson, Arizona, United States, 85745
      • The Oncology Institute of Hope and Innovation
  • California
    • Fountain Valley, California, United States, 92708
      • Orange Coast Memorial Medical Center
    • Long Beach, California, United States, 90806
      • Long Beach Memorial Medical Center
    • Riverside, California, United States, 92506
      • The Oncology Institute of Hope and Innovation
  • Florida
    • Hollywood, Florida, United States, 33021
      • BRCR Medical Center Inc
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
    • Farmington Hills, Michigan, United States, 48334
      • Revive Research Institute
    • Sterling Heights, Michigan, United States, 48314
      • Revive Research Institute
  • Missouri
    • Springfield, Missouri, United States, 65804
      • Mercy Clinic Cancer & Hematology - Chub O'Reilly Cancer Center
  • New Jersey
    • Mullica Hill, New Jersey, United States, 08062
      • Inspira Medical Center Mullica Hill
  • Ohio
    • Cleveland, Ohio, United States, 44109
      • MetroHealth Medical Center
  • Texas
    • Baytown, Texas, United States, 77521
      • Alpha Research Institute, LLC
    • Harlingen, Texas, United States, 78550
      • Valley Cancer Associates
  • Utah
    • Ogden, Utah, United States, 84405
      • Community Cancer Trials of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rituximab plus Zandelisib; Rituximab plus Zandelisib for 6 cycles followed by Zandelisib for 20 cycles	Drug: Zandelisib; Zandelisib 60 mg capsules taken daily for two cycles followed by intermittent schedule starting at Cycle 3; Other Names: ME-401; Drug: Rituximab; Rituximab IV 375 mg/m2 for 6 cycles; Other Names: Rituxan; MabThera
Experimental: Rituximab plus chemotherapy; Rituximab and Bendamustine or Rituximab with (CHOP) for 6 cycles	Drug: Rituximab; Rituximab IV 375 mg/m2 for 6 cycles; Other Names: Rituxan; MabThera; Drug: Bendamustine; Bendamustine IV 90 mg/m2 on Days 1 and 2 for 6 cycles; Other Names: Bendeka, Treanda, Belrapzo; Drug: CHOP; Cyclophosphamide, Vindcristine IV, and Prednisone daily orally; Other Names: cyclophosphamide 750 mg/m2, hydroxydoxorubicin IV 50 mg/m2, vincristine IV 1.4 mg/m2 and prednisone 100 mg daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
Number of Treatment Emergent AEs (Zandelisib When Combined With Rituximab)	Measured by the number of Treatment Emergent AEs	1 year 7 months
Number of SAEs (Zandelisib When Combined With Rituximab)	Measured by the number of SAEs	1 year 7 months
Number of Lab Abnormalities (Zandelisib When Combined With Rituximab)	Measured by the number of laboratory abnormalities	1 year 7 months

Collaborators and Investigators

• Sponsor: MEI Pharma, Inc.
• Collaborators: Kyowa Kirin, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2021
• Primary Completion (Actual): March 20, 2023
• Study Completion (Actual): March 20, 2023

Study Registration Dates

• First Submitted: February 4, 2021
• First Submitted That Met QC Criteria: February 4, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Estimated): November 4, 2024
• Last Update Submitted That Met QC Criteria: October 31, 2024
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, B-Cell; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell, Marginal Zone; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Bendamustine Hydrochloride; Rituximab; Prednisone; Cyclophosphamide; Vincristine
• Other Study ID Numbers: ME-401-004; 2020-004199-16 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No