Zandelisib (ME-401) in Subjects With Follicular Lymphoma or Marginal Zone Lymphoma After Failure of Two or More Prior Therapies (TIDAL)

• ClinicalTrials.gov Identifier: NCT03768505
• Recruitment Status: Active, not recruiting
• First Posted: December 7, 2018
• Last Update Posted: January 13, 2023
• Sponsor: MEI Pharma, Inc.
• Information provided by (Responsible Party): MEI Pharma, Inc.

Study Description

Brief Summary:

This is the study of the PI3Kδ inhibitor Zandelisib (ME-401) in subjects with relapsed/refractory follicular lymphoma or marginal zone lymphoma after failure of at least 2 prior lines of systemic therapy

Condition or disease	Intervention/treatment	Phase
Follicular Lymphoma (FL); Non Hodgkin Lymphoma; Marginal Zone Lymphoma	Drug: Zandelisib (ME-401)	Phase 2

Detailed Description:

This is a global, multicenter open-label, single-arm, Phase 2 study of the PI3Kδ inhibitor Zandelisib (ME-401) in subjects with relapsed/refractory follicular lymphoma or marginal zone lymphoma after failure of at least 2 prior lines of systemic therapy which must have included an anti-CD20 antibody and chemotherapy with an alkylating agent or a purine analogue.

Approximately 180 subjects will be enrolled and treated with Zandelisib (ME-401) on the intermittent schedule.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 180 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: Treatment with Zandelisib (ME-401) (60 mg) given orally once a day on an intermittent schedule
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multicenter, Open Label Single-Arm, Phase 2 Study of Zandelisib (ME-401) in Subjects With Follicular Lymphoma and Marginal Zone Lymphoma After Failure of Two or More Prior Systemic Therapies (The TIDAL Study)
• Actual Study Start Date: June 25, 2019
• Estimated Primary Completion Date: December 2024
• Estimated Study Completion Date: April 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Zandelisib (ME-401) open label; Subjects with relapsed/refractory FL or MZL will be administered 60 mg of ME-401 orally, once a day on an intermittent schedule (IS).	Drug: Zandelisib (ME-401); Zandelisib (ME-401) 60 mg

Outcome Measures

Primary Outcome Measures :

1. Objective response rate (ORR) of ME-401 in relapsed or refractory FL or MZL based on the Independent Review Committee assessment [ Time Frame: 2 years ]
   ORR is measured as the proportion of subjects achieving the best response rating of CR or PR prior to first PD

Secondary Outcome Measures :

1. Duration of response (DOR) [ Time Frame: 2 years ]
   Duration of Response will be measured as the time from documentation from CR or PR to time of disease progression
2. Complete response (CR) rate [ Time Frame: 2 years ]
   Complete response rate will be measured by the number of subjects that achieve CR
3. Progression-free survival (PFS) [ Time Frame: 2 years ]
   Progression-free survival will be measurement of time from initiation of treatment (Day 1) until disease progression or death
4. Overall Survival [ Time Frame: 2 years ]
   Overall survival will be measured as the time from initiation of treatment (Day 1) until death
5. Overall incidence of treatment emergent adverse events (TEAEs) [ Time Frame: 2 years ]
   The incidence of TEAEs is measured by the proportion of subjects with at least one TEAE.
6. PK of ME-401 [ Time Frame: 6 months ]
   The PK of ME-401 will be determined by the peak plasma concentration (Cmax)

Eligibility Criteria

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

Criteria

Inclusion Criteria:

• Histologically confirmed diagnosis as defined in the World Health Organization (WHO) classification scheme

  1. Follicular Lymphoma (FL) limited to Grade 1,2 or 3a or
  2. Marginal Zone Lymphoma (MZL) including nodal, extranodal and splenic MZL
• Subjects that have had progression of disease or had no response to therapy after at least 2 prior systemic therapies for FL or MZL
• Age ≥ 18
• At least one bi-dimensionally measurable nodal lesion > 1.5 cm in its longest diameter by computed tomography (CT) scan as defined by the Lugano Classification
• Adequate hematologic, renal and hepatic parameters at screening unless abnormal values are due to FL per Investigator assessment
• QT-interval corrected according to Fridericia's formula (QTcF) ≤ 450 milliseconds (msec);
• Left ventricular ejection fraction (LVEF) ≥ 45%

Exclusion Criteria:

• Histologically confirmed FL Grade 3b transformation from FL to an aggressive lymphoma
• Known lymphomatous involvement of the central nervous system
• Uncontrolled clinically significant illness
• Ongoing or history of drug-induced pneumonitis
• History of clinically significant cardiovascular abnormalities
• History of clinically significant GI conditions
• Known history of, or active HIV infection

Contacts and Locations

Locations

United States, Arizona

Oncology Institute of Hope and Innovation

Tucson, Arizona, United States, 85710

United States, California

Pacific Cancer Medical Center, Inc.

Anaheim, California, United States, 92801

Tower Hematology Oncology

Beverly Hills, California, United States, 90211

The Oncology Institute of Hope and Innovation

Downey, California, United States, 90241

Sharp Memorial Hospital

San Diego, California, United States, 92123

United States, Florida

H. Lee Moffit Cancer Center

Tampa, Florida, United States, 33612

Cleveland Clinic-Florida

Weston, Florida, United States, 333331

United States, Illinois

Rush University Medical Center

Chicago, Illinois, United States, 60612

Advocate Health & Hospitals Corporation

Niles, Illinois, United States, 61761

United States, Indiana

Investigative Clinical Research of Indiana LLC

Indianapolis, Indiana, United States, 46260

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02215

United States, Michigan

University of Michigan Medical School

Ann Arbor, Michigan, United States, 48109

United States, Montana

St. Vincent Frontier Cancer Center

Billings, Montana, United States, 59102

United States, Nevada

The Oncology Institute of Hope and Innovation

Henderson, Nevada, United States, 89052

United States, New Jersey

Memorial Sloan Kettering

Basking Ridge, New Jersey, United States, 07920

Memorial Sloan Kettering

Middletown, New Jersey, United States, 07748

Memorial Sloan Kettering

Montvale, New Jersey, United States, 07645

United States, New Mexico

San Juan Oncology

Farmington, New Mexico, United States, 87401

United States, New York

Memorial Sloan Kettering

Commack, New York, United States, 11725

Memorial Sloan Kettering

Harrison, New York, United States, 10604

Clinical Research Alliance

Lake Success, New York, United States, 11042

Memorial Sloan Kettering

New York, New York, United States, 10065

Memorial Sloan Kettering

Uniondale, New York, United States, 11553

United States, North Carolina

Duke Cancer Center

Durham, North Carolina, United States, 27710

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

United States, Oregon

Oregon Health and Science University

Portland, Oregon, United States, 97239

United States, Tennessee

Vanderbilt University

Nashville, Tennessee, United States, 37203

United States, Texas

Renovatio Clinical

Houston, Texas, United States, 77056

United States, Washington

Swedish Cancer Institute

Edmonds, Washington, United States, 98026

Swedish Cancer Institute

Seattle, Washington, United States, 98104

Medical Oncology Associates PS

Spokane, Washington, United States, 99208

United States, Wisconsin

University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, United States, 53705

Marshfield Medical Center

Marshfield, Wisconsin, United States, 54449

Australia, Victoria

Peninsula and South Eastern Haematology and Oncology Group

Frankston, Victoria, Australia, 3199

Australia, Western Australia

The Perth Blood Institute

West Perth, Western Australia, Australia, 6005

Australia

Liverpool Hospital

Sydney, Australia, NSW2170

Austria

Kepler Universitatsklinikum GmBH

Linz, Austria, 4021

Medical University of Vienna

Vienna, Austria, 1160

Belgium

AZ Sint-Jan Brugge-Oostende

Brugge, Belgium, 8000

Institut Jules Bordet

Brussels, Belgium, 1000

Cliniques Universitaires Saint-Luc

Brussels, Belgium, 1200

Antwerp University Hospital

Edegem, Belgium, 2650

France

C H de la Cote Basque, Service d'Hematologie

Bayonne, France, 64100

CHD Vendee, Onco-hematologie

La Roche-Sur-Yon Cedex 9, France, 85925

Centre Hospitalier du Mans

Le Mans, France, F720000

Centre Hospitalier de Mulhouse

Mulhouse, France, 68100

Centre Hospitalier Universitaire (CHU) de Poitiers - Hôpital de la Miletrie

Poitiers, France, 86021

Institut Gustave Roussy

Villejuif, France, 94805

Germany

Klinikum Mutterhaus Feldstr

Trier, Rheinland-Pfalz, Germany

Hamatologisch-Onkolgische Praxis

Nordheim, Stolberg, Germany, 52222

Universitatsklinikum Halle

Halle, Germany, 06120

Munich Municipal Hospital

Munich, Germany, 80804

Universitatsklinikum Munster

Münster, Germany, 48149

Universitatsklinikum Ulm

Ulm, Germany, 89081

Italy

Centro di Riferimento Oncologico di Aviano (CRO) IRCCS

Aviano, Italy, 33081

Policlinico Sant'Orsola Malpighi

Bologna, Italy, 40138

IRCCS AOU Policlinico San Martino

Genova, Italy, 16132

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori I.R.S.T.

Meldola, Italy, 47014

UOC Oncoematologia

Napoli, Italy, 80131

Ospedale Santa Maria delle Croci

Ravenna, Italy, 48121

Infermi Hospital Rimini

Rimini, Italy, 47923

Universita Cattolica del Sacro Cuore

Roma, Italy, 00168

IRCCS Regina Elena National Cancer Institute

Rome, Italy, 00144

Azienda Ospedaliera Santa Maria

Terni, Italy, 05100

Ospedale DellAngelo Di Mestre Umberto I

Venice, Italy, 30174

Korea, Republic of

Dong-A University Hospital

Busan, Korea, Republic of, 49201

Pusan National University Hospital

Busan, Korea, Republic of, 49241

Korea University Anam Hospital

Seoul, Korea, Republic of, 02841

Seoul National University Hospital

Seoul, Korea, Republic of, 03080

Asan Medical Center

Seoul, Korea, Republic of, 05505

Samsung Medical Center

Seoul, Korea, Republic of, 06351

Ewha Womans University Mokdong Hospital

Seoul, Korea, Republic of, 07985

The Catholic University of Korea-Seoul St. Marys Hospital

Seoul, Korea, Republic of, 6591

Ulsan University Hospital

Ulsan, Korea, Republic of, 44033

New Zealand

North Shore Hospital

Auckland, New Zealand, 0622

Southern District Hospital

Dunedin, New Zealand, 9054

Poland

Szpital Uniwersytecki nr 2 im.

Bydgoszcz, Poland, 85-168

Pratia MCM Krakow

Kraków, Poland, 30-510

Primary Specialty Oncology

Warszawa, Poland, 02-034

Instytut Hematologii i Transfuzjologii

Warszawa, Poland, 02-776

Dolnoslaskie Centrum Transplantacji Komorkowych z Krajowym Bankiem Dawcow Szpiku

Wroclaw, Poland, 53-439

ojewodzkie Wielospecjalistyczne Centrum

Łódź, Poland, 93-510

Spain

Hospital Universitario de Canarias

La Laguna, Tenerife, Spain, 38320

Hospital Universitari Vall d'Hebron

Barcelona, Spain, 08035

Hospital Universitari Mutua Terrasa

Barcelona, Spain, 08221

ICO-Hospital Duran i Reynals

Barcelona, Spain, 08908

MD Anderson Cancer Center

Madrid, Spain, 28033

Hospital Universitario Ramon y Cajal

Madrid, Spain, 28034

Fundacion Jimenez Diaz

Madrid, Spain, 28040

Hospital Universitario Quiron Salud Madrid

Madrid, Spain, 28223

Complejo Hospitalario de Navarra

Pamplona, Spain, 31008

Hospital Clinico de Salamanca

Salamanca, Spain, 37007

Hospital Universitario Virgen Macarena

Sevilla, Spain, 41009

Hospital Virgen del Rocio

Sevilla, Spain, 41013

Miguel Servet Hospital

Zaragoza, Spain, 50009

Switzerland

Ente Ospedaliero Cantonale (EOC)

Bellinzona, Switzerland, 6500

Taiwan

China Medical University Hospital

Taichung, Taiwan, 40447

National Cheng Kung University Hospital

Tainan City, Taiwan, 70403

Chi-Mei Medical Center, Liouying

Tainan, Taiwan, 736

National Taiwan University Hospital NTUH

Taipei City, Taiwan, 10002

United Kingdom

North Wales Cancer Treatment Centre, Glan Clwyd Hospital

Rhyl, Denbighire, United Kingdom, LL185UJ

Royal Marsden Hospital

London, Sutton, United Kingdom, SM25PT

Nottingham University Hospital

Nottingham, UK, United Kingdom, NG51PB

Belfast Health and Social Care Trust - Belfast City Hospital

Belfast, United Kingdom, 28040

Royal Cornwall Hospital

Cornwell, United Kingdom, TR1 3LJ

e Clatterbridge Cancer Centre

Liverpool, United Kingdom, L78XP

Royal Liverpool University Hospital

Liverpool, United Kingdom, L78XP

Lewisham and Greenwich University Hospital Lewisham

London, United Kingdom, SE136LH

St George's Hospital

London, United Kingdom, SW170QT

Centre for Haematology, Imperial College London

London, United Kingdom, W12ONN

The Christie NHS Foundation Trust

Manchester, United Kingdom, M20

Norfolk and Norwich University Hospital NHS Foundation Trust

Norwich, United Kingdom, NR4 7UY

Oxford University Hospitals

Oxford, United Kingdom, 0X46LB

Royal Hallamshire Hospital

Sheffield, United Kingdom, S102JF

Sponsors and Collaborators

MEI Pharma, Inc.

More Information

• Responsible Party: MEI Pharma, Inc.
• ClinicalTrials.gov Identifier: NCT03768505
• Other Study ID Numbers: ME-401-003; 2018-002896-17 ( EudraCT Number )
• First Posted: December 7, 2018
• Last Update Posted: January 13, 2023
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• 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, Follicular; Lymphoma, B-Cell, Marginal Zone; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell