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

Sponsor
MEI Pharma, Inc. (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04745832
Collaborator
Kyowa Kirin, Inc. (Industry)
534
Enrollment
135
Locations
2
Arms
120.6
Anticipated Duration (Months)
4
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 3

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 Design

Study Type:
Interventional
Anticipated Enrollment :
534 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Intervention Model Description:
Arm 1: Rituximab plus Zandelisib Arm 2: Rituximab plus chemotherapy (CHOP or Bendamustine)Arm 1: Rituximab plus Zandelisib Arm 2: Rituximab plus chemotherapy (CHOP or Bendamustine)
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Aug 13, 2021
Anticipated Primary Completion Date :
Apr 1, 2026
Anticipated Study Completion Date :
Sep 1, 2031

Arms and Interventions

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

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Progression Free Survival [5 years]

      PFS is defined as the time from randomization date until the date of disease progression, or death from any cause

    Secondary Outcome Measures

    1. Overall Response Rate (ORR) [5 years]

      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.

    2. Complete Response Rate (CRR) [5 years]

      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).

    3. Overall Survival [10 years]

      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.

    4. Number of Treatment Emergent AEs (Zandelisib when combined with Rituximab) [5 years]

      Measured by the number of Treatment Emergent AEs

    5. Number of SAEs (Zandelisib when combined with Rituximab) [5 years]

      Measured by the number of SAEs

    6. Number of Lab Abnormalities (Zandelisib when combined with Rituximab) [5 years]

      Measured by the number of laboratory abnormalities

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 The Oncology Institute of Hope and Innovation Tucson Arizona United States 85745
    2 Orange Coast Memorial Medical Center Fountain Valley California United States 92708
    3 Long Beach Memorial Medical Center Long Beach California United States 90806
    4 The Oncology Institute of Hope and Innovation Riverside California United States 92506
    5 BRCR Medical Center Inc Hollywood Florida United States 33021
    6 Henry Ford Hospital Detroit Michigan United States 48202
    7 Revive Research Institute Farmington Hills Michigan United States 48334
    8 Revive Research Institute Sterling Heights Michigan United States 48314
    9 Mercy Clinic Cancer & Hematology - Chub O'Reilly Cancer Center Springfield Missouri United States 65804
    10 Inspira Medical Center Mullica Hill Mullica Hill New Jersey United States 08062
    11 MetroHealth Medical Center Cleveland Ohio United States 44109
    12 Alpha Research Institute, LLC Baytown Texas United States 77521
    13 Valley Cancer Associates Harlingen Texas United States 78550
    14 Community Cancer Trials of Utah Ogden Utah United States 84405
    15 The Perth Blood Institute (PBI) West Perth Australia 6005
    16 Westmead Hospital Westmead Australia 2145
    17 AZ Sint-Jan Burgge-Oostende AV Brugge Belgium 8000
    18 UZ Brussel Brussel Belgium 1090
    19 Universitair Ziekenhuis Antwerpen Edegem Belgium 655, 2650
    20 Center Hospitalier de Jolimont Haine-Saint-Paul Belgium 7100
    21 UZ Leuven Campus Gasthuisberg Leuven Belgium
    22 Eastern Regional Health Authority Saint John's Newfoundland and Labrador Canada A1B3V6
    23 Centre intégré universitaire de santé et de services sociaux de l'Estrie Sherbrooke Quebec Canada JIH5N4
    24 McGill University Health Centre Québec Canada H4A 3J1
    25 Centre Hospitalier De Dunkerque - Service d'hématologie Le Mans France 72000
    26 Centre Hospitalier du Mans Le Mans France 72000
    27 Hôpital Saint-Louis Paris France 75010
    28 CHU de Bordeaux - Maladies Du Sang, Centre François Magendie Pessac France 33600
    29 Centre Henri Becquerel, Service d'Hematologie Rouen France 76038
    30 CHU de Tours, Hôpital Bretonneau Centre Tours Cedex 1 France 37044
    31 Institut De Cancerologie Gustave Roussy Villejuif France 94805
    32 LTD Israeli-Georgian Medical Research Clinic "Helsicore" Tbilisi Georgia 0112
    33 M. Zodelava Hematology Center Tbilisi Georgia 0112
    34 J.S.C. K. Eristavi National Center of Experimental and Clinic Tbilisi Georgia 0159
    35 LTD "Medinvest" Institute of Hematology and Transfusiology Tbilisi Georgia 0186
    36 General Hospital of Athens "Laiko", Department of Haematology and Bone Marrow Transplantation Athens Greece 11527
    37 University General Hospital of Ioannina, Department of Haematology Ioánnina Greece 455 00
    38 University General Hospital of Patras "Panagia H. Voitheia" Patras Greece 26504
    39 General Hospital of Thessaloniki "G. Papanikolaou" Thessaloníki Greece 57010
    40 Országos Onkológiai Intézet Gyógyszerterápiás Központ Hematológia és Lymphoma Osztály Budapest Hungary H-1122
    41 Debreceni Egyetem Klinikai Kozpont, Belgyogyaszati Klinika Debrecen Hungary H-4032
    42 Szabolcs-Szatmar-Bereg Megyei Korhazak es Egyetemi Oktatokorhaz, Nyiregyhaza Hungary H-4400
    43 SOC Oncologia Medica e dei Tumori Immunocorrelati Aviano Italy 33081
    44 UO di Ematologia "L.e A.Seragnoli" Policlinico Sant'Orsola Malpighi Bologna Italy 40138
    45 U.O. Ematologia, Azienda Ospedaliera S. Croce e Carle Cuneo Italy 12100
    46 U.O. Ematologia - Azienda Ospedaliero-Universitaria Careggi Firenze Italy 50134
    47 SC Oncologia Medica Meldola Italy 47014
    48 UOC Ematologia, Presidio Ospedaliero Papardo Messina Italy 98158
    49 UO Ematologia 1 Azienda ULSS 3 Serenissima, Distertto del veneziano - Ospedale dell'Angelo di Mestre Mestre Italy 30174
    50 Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano Milano Italy 20122
    51 Dipartimento di Oncoematologia, Unità Linfomi, Ospedale Milano Italy 20132
    52 Divisione Oncoematologia, Istituto Europeo di Oncologia Milano Italy 20141
    53 Azienda Ospedaliera Ospedali Riuniti Via Sofia Palermo Italy 90146
    54 UO Ematologia, Ospedale Civile S.Maria delle Croci Ravenna Italy 48121
    55 UO Ematologia, Ospedale Infermi di Rimini AUSL Romagna Rimini Italy 47923
    56 Istituti Fisioterapici Ospitalieri Roma Italy 00144
    57 S.C. Oncoematologia Azienda Ospedaliera Santa Maria Terni Italy 05110
    58 National Hospital Organization Nagoya Medical Center Naka-ku Aichi Japan 460-0001
    59 National Hospital Organization Shikoku Cancer Center Matsuyama-Shi Ehime Japan 791-0280
    60 National Hospital Organization Kyushu Cancer Center Minami Fukuoka Japan 811-1395
    61 Gunma University Hospital Maebashi Gunma Japan 371-8511
    62 Kobe City Medical Center General Hospital Kobe Hyogo Japan 650-0047
    63 Kagoshima University Hospital Sakuragaoka Kagoshima-Shi, Kagoshima Japan 890-8520
    64 University Hospital Kyoto Prefectural University of Medicine Kamigyo-ku Kyoto Japan 602-8566
    65 Kindai University Hospital Osakasayama-shi Osaka Japan 589-8511
    66 Anjo Kosei Hospital Aichi Japan 446-8602
    67 Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital Aichi Japan 466-8650
    68 Aomori Prefectural Central Hospital Aomori Japan 030-8553
    69 Chiba Cancer Center Chiba Japan 260-8717
    70 Kyushu University Hospital Fukuoka Japan 812-8582
    71 Chugoku Central Hospital Hiroshima Japan 720-0001
    72 Hokkaido University Hospital Hokkaido Japan 060-8648
    73 National Hospital Organization Kumamoto Medical Center Kumamoto Japan 860-0008
    74 Kyoto University Hospital Kyoto Japan 606-8507
    75 National University Corporation Tohoku University Hospital Miyagi Japan 980-8574
    76 Aichi Cancer Center Hospital Nagoya Japan 464-8681
    77 Okayama University Hospital Okayama Japan 700-8558
    78 Osaka International Cancer Institute Osaka Japan 541-8567
    79 Osaka University Hospital Osaka Japan 565-0871
    80 Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Tokyo Japan 113-8677
    81 The Cancer Institute Hospital of Japanese Foundation For Cancer Research Tokyo Japan 135-8550
    82 Keio University Hospital Tokyo Japan 160-8582
    83 Inje University Busan Paik Hospital Busan Korea, Republic of 47392
    84 Dong-A university Hospital Busan Korea, Republic of 49201
    85 Pusan National University Hospital Busan Korea, Republic of 49241
    86 Kyungpook National University Hospital Daegu Korea, Republic of 41944
    87 Chonnam National University Hwasun Hospital Jeollyang Korea, Republic of 58128
    88 Korea University Anam Hospital Seoul Korea, Republic of 02841
    89 Seoul National University Hospital Seoul Korea, Republic of 03080
    90 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 03722
    91 Asan Medical Center Seoul Korea, Republic of 05505
    92 Samsung Medical Center Seoul Korea, Republic of 06351
    93 The Catholic University of Korea Seoul Korea, Republic of 06591
    94 Ewka Womans University Mokdong Hospital Seoul Korea, Republic of 07985
    95 Ulsan University Hospital Ulsan Korea, Republic of 44033
    96 Albert Schweizer Ziekenhuis, Hematology Department Dordrecht Netherlands 3318
    97 Spaarne Gasthuis, Oncology Department Hoofddorp Netherlands 2134
    98 Canterbury District Health Board, Haematology Department Christchurch New Zealand 8011
    99 Dunedin Hospital, Southern Blood and Cancer Service Dunedin New Zealand 9016
    100 Klinika Hematologii, Szpital Uniwersytecki Bydgoszcz Poland 85-168
    101 Pratia MCM Krakow Kraków Poland 30-510
    102 ARS Medical - Szpital, Oddzial hematologiczny Piła Poland 64-920
    103 Centrum Medyczne Pratia Poznan Skorzewo Poland 60-185
    104 University Clinical Center of Serbia, Clinic for Hematology Belgrade Serbia 11000
    105 Zvezdara University Medical Center, Clinical department for Hematology and Oncology Belgrade Serbia 11000
    106 Clinical Hospital Center "Zemun", Clinic for Internal Medicine, Department for Hematology Belgrade Serbia 11080
    107 Oncology Institute of Vojvodina, Clinic for Internal Oncology Kamenica Serbia 21204
    108 Clinical Center of Vojvodina, Clinic for Hematology Novi Sad Serbia 21000
    109 Hospital Universitario Quironsalud Alcorcón Madrid Spain 28223
    110 Hospital Universitari Vall d'Hebron, Vall d'Hebron Institute of Oncology Barcelona Spain 08035
    111 Hospital Universitario Mútua Terrassa Barcelona Spain 08221
    112 Institut Catalá d'Oncologia, Hospital Duran i Reynals Barcelona Spain 08908
    113 Hospital Universitario Ramón y Cajal Madrid Spain 28034
    114 Complejo Hospitalario de Navarra Navarro Spain 31008
    115 Hospital Universitario de Canarias Santa Cruz De Tenerife Spain 38320
    116 Hospital Universitario Virgen Macarena Sevilla Spain 41009
    117 Hospital Universitario Miguel Servet Zaragoza Spain 50009
    118 China Medical University Hospital Taichung Taiwan 404332
    119 Taichung Veterans General Hospital Taichung Taiwan 40705
    120 Chi Mei Hospital Tainan City Taiwan 73657
    121 National Cheng Kung University Hospital Tainan Taiwan 704
    122 Gazi University Health Research and Application Hospital, Hematology Department Ankara Turkey 29 06560
    123 Erciyes University Medical Faculty, Department of Hematology Kayseri Turkey 38039
    124 Ondokuz Mayis University Medical Faculty, Hematology Department Samsun Turkey 55200
    125 Namik Kemal University Hospital Tekirdağ Turkey 59100
    126 Karadeniz Technical University Medical Faculty Department of Hematology Trabzon Turkey 61080
    127 North Wales Cancer Treatment Centre Bodelwyddan Denbighshire United Kingdom LL18 5UJ
    128 Royal Cornwall Hospital Cornwell United Kingdom TR1 3LJ
    129 Department of Haematology St. George's University of London London United Kingdom SW17 0RE
    130 The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital London United Kingdom SW3 6JJ
    131 Imperial College Healthcare NHS Trust Hammersmith Hospital London United Kingdom W12 0HS
    132 The Christie NHS Foundation Trust Manchester United Kingdom M20 4BX
    133 Genesis Care Oxford Oxford United Kingdom OX4 6LB
    134 University Hospitals Plymouth NHS Trust, Derriford Hopital Plymouth United Kingdom PL6 8DH
    135 The Royal Marsden NHS Foundation Trust - Royal Marsden Hospital Surrey Quays United Kingdom SM2 5PT

    Sponsors and Collaborators

    • MEI Pharma, Inc.
    • Kyowa Kirin, Inc.

    Investigators

    None specified.

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    MEI Pharma, Inc.
    ClinicalTrials.gov Identifier:
    NCT04745832
    Other Study ID Numbers:
    • ME-401-004
    • 2020-004199-16
    First Posted:
    Feb 9, 2021
    Last Update Posted:
    Jul 28, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Lymphoma
    Lymphoma, Non-Hodgkin
    Lymphoma, B-Cell, Marginal Zone
    Prednisone
    Cyclophosphamide
    Bendamustine Hydrochloride
    Rituximab
    Vincristine

    Study Results

    No Results Posted as of Jul 28, 2022