stop_circleTerminated/Withdrawn

Lymphoma, Non-Hodgkin

Study of copanlisib in combination with standard immunochemotherapy in relapsed indolent non-Hodgkin’s lymphoma (iNHL)

Trial purpose

The purpose of this study is to assess whether copanlisib in combination with standard immunochemotherapy (rituximab in combination with bendamustine [R-B] and rituximab in combination with a 4 drug combination of cyclophosphamide, doxorubicin, vincristine and prednisone/prednisolone [R-CHOP]) is effective and safe, compared with placebo in combination with standard immunochemotherapy (R-B or R-CHOP) in patients with relapsed iNHL who have received at least one, but at most three, lines of treatment, including rituximab-based immunochemotherapy and alkylating agents.

Key Participants Requirements

Sex

Both

Age

18 - N/A
  • - Histologically confirmed diagnosis of B lymphocyte antigen CD20 positive iNHL with histological subtype limited to:
     -- Follicular lymphoma G1-2-3a
     -- Small lymphocytic lymphoma with absolute lymphocyte count <5x10E9/L at study entry
     -- Lymphoplasmacytoid lymphoma / Waldenström macroglobulinemia (LPL / WM)
     -- Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)
    - Patients must have relapsed (recurrence after complete response or presented progression after partial response) or progressed after at least one but at most three prior lines of therapy, including rituximab, and/or rituximab biosimilars, and/or anti-CD20 monoclonal antibody (e.g. obinutuzumab) -based immunochemotherapy and alkylating agents (if given concomitantly is considered one line of therapy). A previous regimen is defined as one of the following: at least 2 months of single-agent therapy (less than 2 months of therapy with single agent rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody can be considered a previous regimen in the case the patient responded to it); at least 2 consecutive cycles of polychemotherapy; autologous transplant; or radioimmunotherapy. Previous exposure to other PI3K Inhibitors (except copanlisib) is acceptable provided there is no resistance (resistance defined as no response (response defined as partial response [PR] or complete response [CR]) at any time during therapy, or progressive disease (PD) after any response (PR/CR) or after stable disease within 6 months from the end of the therapy with a PI3K inhibitor.
    - Non-WM patients must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) according to the Lugano Classification. For patients with splenic MZL this requirement may be restricted to splenomegaly alone since that is usually the only manifestation of measurable disease.
    - Patients affected by WM who do not have at least one bi-dimensionally measurable lesion in the baseline radiologic assessment must have measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level ≥ 2 x upper limit of normal and positive immunofixation test.
    - Male or female patients ≥ 18 years of age
    - Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
    - Life expectancy of at least 3 months
    - Availability of fresh tumor tissue and/or archival tumor tissue at Screening
    - Adequate baseline laboratory values as assessed within 7 days before
    starting study treatment.
    - Left ventricular ejection fraction ≥ 50%
  • - Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed disease, or chronic lymphocytic leukemia. In patients with clinical suspicion of transformed disease, a fresh biopsy is recommended.
    - Rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody (e.g. obinutuzumab) resistance at any line of therapy (resistance defined as lack of response, or progression within 6 months of the last date of rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody administration, including maintenance with these drugs).
    - HbA1c > 8.5% at screening
    - History or concurrent condition of interstitial lung disease and/or severely impaired lung function (as judged by the investigator)
    - Known lymphomatous involvement of the central nervous system
    - Known history of human immunodeficiency virus (HIV) infection
    - Hepatitis B (HBV) or hepatitis C (HCV) infection. Patients positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-DNA, these patients should receive prophylactic antiviral therapy as per rituximab label. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.
    - Cytomegalovirus (CMV) infection. Patients who are CMV PCR positive at baseline will not be eligible.CMV PCR test is considered positive if, the result can be interpreted as a CMV viremia according to local standard of care.
    - Uncontrolled hypertension despite optimal medical management (per investigator´s assessment)
    - Congestive heart failure > New York Heart Association (NYHA) class 2

Trial summary

Enrollment Goal
547
Trial Dates
January 2016 - November 2023
Phase
Phase 3
Could I Receive a placebo
Yes
Products
Copanlisib/RB or RCHOP (BAY80-6946)
Accepts Healthy Volunteer
No

Where to participate

StatusInstitutionLocation
Completed
The Alfred HospitalMelbourne, 3004, Australia
Completed
Klinikum der Universität München GrosshadernMünchen, 81377, Germany
Completed
Universitätsklinikum Münster (UKM)Münster, 48149, Germany
Completed
HUS, Meilahden sairaalaHelsinki, FIN-00260, Finland
Completed
Tampereen yliopistollinen sairaalaTampere, 33520, Finland
Withdrawn
Keski-Suomen sairaala NovaJyväskylä, 40620, Finland
Completed
National Cancer Center SingaporeSingapore, 168583, Singapore
Completed
National Taiwan University HospitalTaipei, 100, Taiwan
Completed
Taipei Veterans General HospitalTaipei, 11217, Taiwan
Completed
Rigshospitalet - HjertesygdommeKøbenhavn Ø, 2100, Denmark
Withdrawn
Hôpital Henri MondorCRETEIL, 94010, France
Withdrawn
Centre Henri BecquerelRouen, 76038, France
Completed
Hôpital DupuytrenLIMOGES CEDEX, 87042, France
Completed
Hôpital de la MilétriePOITIERS, 86021, France
Completed
Wojew. Szpital Specjalistyczny im. M. KopernikaLodz, 93-513, Poland
Withdrawn
Hospital Clínic i Provincial de BarcelonaBarcelona, 8036, Spain
Completed
UZ Leuven GasthuisbergLEUVEN, 3000, Belgium
Withdrawn
Edith Wolfson Medical Center | Internal Medicine DepartmentHolon, 5822012, Israel
Completed
Seoul National University HospitalSeoul, 3080, Korea,_republic_of
Completed
Samsung Medical CenterSeoul, 6351, Korea,_republic_of
Completed
Hospital Universitario Clinica Puerta de HierroMajadahonda, 28222, Spain
Completed
UZ GentGENT, 9000, Belgium
Withdrawn
A.O.U. di Bologna Policlinico S.Orsola MalpighiBologna, 40138, Italy
Completed
Humanitas Mirasole S.p.A.Milano, 20089, Italy
Withdrawn
Freeman HospitalNewcastle, NE7 7DN, United Kingdom
Completed
Fiona Stanley HospitalMurdoch, 6961, Australia
Withdrawn
Royal Brisbane & Women's HospitalBrisbane, 4029, Australia
Completed
Dokuz Eylul Universitesi Tip FakultesiIzmir, 35100, Turkey
Completed
Marmara Uni. Tip Fak. Pendik EAH Hematoloji BDIstanbul, 34899, Turkey
Completed
Ashford Cancer Centre Research Pty LtdKurralta Park, 5037, Australia
Completed
Fakultni nemocnice Kralovske VinohradyPraha 10, 10034, Czech Republic
Withdrawn
Hackensack University Medical CenterHackensack, 07601, United States
Completed
Memorial Sloan-Kettering Cancer CenterNew York, 10065, United States
Completed
Gabrail Cancer CenterCanton, 44718, United States
Withdrawn
Medical Oncology Associates, PSSpokane, 99208-1129, United States
Withdrawn
Detroit Clinical Research CenterFarmington Hills, 48334, United States
Withdrawn
Compassionate Cancer Care Medical Group, Inc.Fountain Valley, 92708, United States
Withdrawn
Royal Marsden NHS Trust (Surrey)Sutton, SM2 5PT, United Kingdom
Withdrawn
GZA ZiekenhuizenWilrijk, 2610, Belgium
Withdrawn
AZ Groeninge Campus KennedylaanKORTRIJK, 8500, Belgium
Completed
Tianjin Union Medicine Centre (People's Hospital of Tianjin)Tianjin, 300121, China
Completed
The 1st Affiliated Hospital of Zhejiang UniversityHangzhou, 310000, China
Completed
Zhejiang Cancer HospitalHangzhou, 310022, China
Completed
Fudan University Shanghai Cancer CenterShanghai, 200000, China
Completed
1st Affiliated hospital of Soochow UniversitySuzhou, 215000, China
Withdrawn
Cancer Hospital, Chinese Academy of Medical SciencesBeijing, 100000, China
Completed
Fifth Medical Center, General Hospital of the Chinese PeopleBeijing, 100000, China
Withdrawn
Frankston HospitalFrankston, 3199, Australia
Withdrawn
The Kinghorn Cancer Centre - Medical Oncology DepartmentDarlinghurst, 2010, Australia
Completed
FuJian Medical University Union HospitalFuzhou, 350000, China
Completed
Beijing Friendship Hospital, Capital Medical UniversityBeijing, 100050, China
Completed
Jiangsu Cancer HospitalNanjing, 210000, China
Completed
Singleton HospitalSwansea, SA2 8QA, United Kingdom
Recruiting
Royal Marsden Hospital (London)London, SW3 6JJ, United Kingdom
Completed
Dorset County HospitalDorchester, DT1 2JY, United Kingdom
Completed
West China Hospital Sichuan UniversityChengdu, 610041, China
Completed
Oulun yliopistollinen sairaalaOulu, 90220, Finland
Completed
Turun yliopistollinen keskussairaalaTurku, 20520, Finland
Completed
Hadassah Hebrew University Hospital Ein KeremJerusalem, 9112001, Israel
Completed
Rambam Health CorporationHaifa, 3109601, Israel
Completed
Shamir Medical Center (Assaf Harofeh)Zerifin, 7030000, Israel
Completed
Mater Misericordiae University HospitalDublin, D07R2WY, Ireland
Completed
Cork University HospitalCork, T12DC4A, Ireland
Completed
Centre Universitaire de Sante de l'EstrieSherbrooke, J1H 5N4, Canada
Completed
Hopital Maisonneuve-RosemontMontreal, H1T 2M4, Canada
Completed
Hopital de L'Enfant JesusQuebec City, G1J 1Z4, Canada
Completed
Calvary Mater Hospital NewcastleWaratah, 2298, Australia
Withdrawn
Clínica Santa MaríaSantiago, 7520378, Chile
Completed
Instituto Nacional del CáncerSantiago, 838-0455, Chile
Completed
Centro de Investigaciones Clínicas Vina del Mar Ltda.Vina del Mar, 2540364, Chile
Withdrawn
Fundación Arturo López PerezSantiago, 7500921, Chile
Completed
Hôpital Saint LouisPARIS, 75010, France
Completed
Hôpital Saint-EloiMONTPELLIER CEDEX, 34059, France
Active, not recruiting
St George's HospitalKogarah, 2217, United Kingdom
Completed
Guangdong Provincial People's HospitalGuangzhou, 510000, China
Completed
Tianjin Medical University Cancer Institute & HospitalTianjin, 300000, China
Completed
Asan Medical CenterSeoul, 138-736, Korea,_republic_of
Completed
Severance Hospital, Yonsei University Health SystemSeoul, 03722, Korea,_republic_of
Withdrawn
Pusan National University HospitalBusan, 49241, Korea,_republic_of
Completed
Northwick Park HospitalHarrow, HA1 3UJ, United Kingdom
Completed
Royal Devon & Exeter HospitalExeter, EX2 5DW, United Kingdom
Completed
Changhua Christian HospitalChanghua, 50006, Taiwan
Completed
National Cheng Kung University HospitalTainan, 704, Taiwan
Completed
Chang Gung Memorial Hospital KaohsiungKaohsiung, 833, Taiwan
Completed
IRCCS Fondazione Policlinico San MatteoPavia, 27100, Italy
Completed
A.O.U. Ospedali Riuniti "Umberto I - G.M.Lancisi - G.Salesi"Ancona, 60126, Italy
Completed
Narodny onkologicky ustavBratislava, 833 10, Slovakia
Withdrawn
Vychodoslovensky onkologicky ustav a.s.Kosice, 041 91, Slovakia
Withdrawn
Centre Hospitalier Lyon SudPIERRE BENITE, 69495, France
Completed
Centre Hospitalier Universite de GrenobleGrenoble, 38043, France
Completed
Centre François Magendie - PessacPESSAC, 33600, France
Withdrawn
Centre Léon Bérardlyon, 69008, France
Withdrawn
Kantonsspital Baselland - Standort LiestalLiestal, 4410, Switzerland
Withdrawn
Ospedale Regionale BellinzonaBellinzona, 6500, Switzerland
Completed
Ankara Universitesi Tip Fakultesi HastanesiAnkara, 6100, Turkey
Completed
Karadeniz Teknik Universitesi Tip FakultesiTrabzon, 61080, Turkey
Completed
Erciyes Universitesi Tip FakultesiKayseri, 38039, Turkey
Completed
Xinhua Hos Affiliated to SH Jiaotong Uni School of MedicineShanghai, 200092, China
Completed
Istanbul Universitesi Istanbul Tip FakultesiIstanbul, 34093, Turkey
Withdrawn
CHU de Caen - Hôpital Côte de NacreCAEN cedex 9, 14033, France
Completed
Jilin Cancer HospitalChangchun, 130000, China
Completed
Henan Cancer HospitalZhengzhou, 450000, China
Completed
Tumor Hospital of Hebei ProvinceHebei, 050000, China
Completed
Prince of Wales HospitalShatin, MISSING, Hong Kong
Withdrawn
Queen Mary HospitalHong Kong, Hong Kong
Withdrawn
Tuen Mun HospitalHongkong, Hong Kong
Withdrawn
Queen Elizabeth Hospital Hong KongKowloon, Hong Kong
Completed
Med. Fakultät der Martin-Luther-Universität Halle-WittenbergHalle, 6120, Germany
Completed
Fakultni Nemocnice Hradec KraloveHradec Kralove, 500 05, Czech Republic
Completed
Ege Universitesi Tip FakultesiIzmir, 35100, Turkey
Completed
Trakya Univ. Tip Fak.Edirne, 22030, Turkey
Completed
Ondokuz Mayis Uni Tip FakultesiSamsun, 55139, Turkey
Completed
Institut Jules Bordet/Jules Bordet InstituutBruxelles, 1070, Belgium
Completed
CHU de LiègeLIEGE, 4000, Belgium
Completed
Albert Alberts Stem Cell Transplant Research CentrePretoria, 44, South Africa
Completed
Outeniqua Cancercare Oncology UnitGeorge, 6530, South Africa
Completed
Cancercare LangenhovenPort Elizabeth, 6045, South Africa
Completed
State Institution - Institute of Blood Pathology and Transfusion Medicine NAMS of UkraineLviv, 79044, Ukraine
Completed
Governmental Noncommercial Institution "National Cancer InstituteKyiv, 03022, Ukraine
Completed
CNE "Zaporizhzhia Regional Clinical Hospital" of Zaporizhzhia regional councilZaporizhzhya, 69600, Ukraine
Completed
CNE "Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of the Cherkasy Regional Council"Cherkasy, 18009, Ukraine
Completed
IPO PortoPorto, 4200-072, Portugal
Withdrawn
Centro Hospitalar Universitario de Sao Joao | Polo Porto - Centro de Investigacao e Ensaios ClinicosPorto, 4200-319, Portugal
Completed
Centro Hospitalar Universitario do PortoPorto, 4099-001, Portugal
Completed
Centro Hospitalar Vila Nova de Gaia e Espinho | Unit 1 - Clinical Research CenterPorto, 4434-502, Portugal
Completed
Centro Clinico Academico Braga | Braga, PortugalBraga, 4710-243, Portugal
Completed
Centro Multidisciplinar de Estudos Clínicos EPP - Ltda.São Bernardo do Campo, 09715-090, Brazil
Completed
IRCCS Ospedale Policlinico San MartinoGenova, 16132, Italy
Completed
Odense Universitetshospital - Hæmatologisk afdelingOdense C, 5000, Denmark
Withdrawn
Klinikum Wels-Grieskirchen GmbHWels, 4600, Austria
Withdrawn
Kantonsspital AarauAarau, 5001, Switzerland
Withdrawn
Royal Cornwall HospitalTruro, TR1 3LJ, United Kingdom
Completed
Institut Català d'Oncologia HospitaletHospitalet de Llobregat, 08907, Spain
Completed
Hospital Regional de Malaga | OncologiaMalaga, 29010, Spain
Withdrawn
Complejo Hospitalario Universitario A Coruña | OncologiaA Coruña, 15006, Spain
Completed
Hospital Clínico Universitario Lozano BlesaZaragoza, 50009, Spain
Completed
The Affiliated Hospital of Qingdao Universityshandong, 266000, China
Completed
Haematologie-Onkologie im Zentrum MVZ GmbHAugsburg, 86150, Germany
Completed
Institut Català d'Oncologia BadalonaBadalona, 8916, Spain
Completed
Flinders Medical CentreBedford Park, 5042, Australia
Completed
General Hospital of Athens LAIKOAthens, 11527, Greece
Completed
University General Hospital of Athens "ATTIKON"Chaidari, 12462, Greece
Completed
EVANGELISMOS General Hospital of AthensAthens, 106 76, Greece
Completed
University General Hospital of PatrasPatras, 26500, Greece
Completed
Univ. General Hospital of LarissaLarissa, 41110, Greece
Withdrawn
PAPANIKOLAOU General Hospital of ThessalonikiThessaloniki, 57010, Greece
Withdrawn
Meir Medical CenterKfar Saba, 4428164, Israel
Completed
Hospital de Clinicas de Porto Alegre | Clinical Research Center - Surgery Research CenterPorto Alegre, 90035-903, Brazil
Completed
Hospital Israelita Albert Einstein | Morumbi - Clinical Research DepartmentSao Paulo, 05651-901, Brazil
Completed
Instituto Nacional do Cancer Jose Alencar Gomes da SilvaRio de Janeiro, 20231-050, Brazil
Withdrawn
Hosp Bruno Born Sociedade Beneficência e Caridade de LajeadoLajeado, TBC, Brazil
Completed
Centro de Pesquisas OncológicasFlorianópolis, 88034-000, Brazil
Withdrawn
Casa de Saúde Santa MarcelinaSão Paulo, 08.270-070, Brazil
Completed
Centro Integrado de Oncologia de CuritibaCuritiba, 80810-050, Brazil
Completed
UMHAT Sveti GeorgiPlovdiv, 4000, Bulgaria
Completed
University Multiprofile Hosp. for Active Treat. Sveti IvanSofia, 1431, Bulgaria
Completed
SHATHD Spec. Hospi. for Active Treatm. of Haematol. Dis. EADSofia, 1756, Bulgaria
Completed
Multiprofile Hospital for Active Treatment Hristo Botev ADVratsa, 3000, Bulgaria
Completed
Semmelweis UniversityBudapest, 1083, Hungary
Completed
Pecsi Tudomanyegyetem Klinikai KozpontPecs, 7623, Hungary
Completed
Somogy Varmegyei Kaposi Mor Oktato KorhazKaposvar, 7400, Hungary
Completed
Komarom-Esztergom Varmegyei Szent Borbala KorhazTatabanya, 2800, Hungary
Completed
Semmelweis UniversityBudapest, 1083, Hungary
Withdrawn
St. Petersburg Clinical Hospital of RASSt. Petersburg, 194017, Russia
Completed
Oncology Dispensary #2Sochi, 354057, Russia
Completed
Republican Clinical Oncology DispensaryUfa, 450054, Russia
Completed
RSRI of Hematology and TransfusiologySaint-Petersburg, 191024, Russia
Withdrawn
Regional Clinical Hospital YaroslavlYaroslavl, 150062, Russia
Completed
Siberian State Medical UniversityTomsk, 634050, Russia
Withdrawn
Institut de Cancérologie de l'Ouest - Saint HerblainSaint-Herblain, 44800, France
Completed
Oncologianova GmbHRecklinghausen, 45659, Germany
Withdrawn
Bacs-Kiskun Varmegyei OktatokorhazKecskemét, 6000, Hungary
Completed
Eastern Health Integrated Renal ServiceBox Hill, 3128, Australia
Completed
Stauferklinikum Schwäbisch-GmündMutlangen, 73557, Germany
Withdrawn
Mayo Clinic - RochesterRochester, 55905, United States
Withdrawn
Hartford HospitalHartford, 06102-5037, United States
Completed
Singapore General HospitalSingapore, 169608, Singapore
Completed
National University HospitalSingapore, 119074, Singapore
Withdrawn
Raffles HospitalSingapore, 188770, Singapore
Withdrawn
Onkolog. Gemeinschaftspraxis Dres. D.Reichert & J.JanssenWesterstede, 26655, Germany
Withdrawn
University of Mississippi Medical Center | Shafi GroupJackson, 39216, United States
Withdrawn
Universität Rostock - Medizinische FakultätRostock, 18057, Germany
Withdrawn
Alaska Cancer Treatment CenterAnchorage, 99503, United States
Withdrawn
Prairie Lakes Cancer CenterWatertown, 57201, United States
Withdrawn
Mountain Blue Cancer Care CenterEnglewood, 80113, United States
Completed
National Cancer Center HospitalChuo-ku, 104-0045, Japan
Completed
Tohoku University HospitalSendai, 980-8574, Japan
Withdrawn
National Hospital Organization Nagoya Medical CenterNagoya, 460-0001, Japan
Completed
Nagoya City University HospitalNagoya, 467-8602, Japan
Withdrawn
Kyoto Prefectural University of MedicineKyoto, 602-8566, Japan
Completed
Kobe University HospitalKobe, 650-0017, Japan
Completed
Orszagos Onkologiai IntezetBudapest, 1122, Hungary
Withdrawn
Kaluga Regional Clinical HospitalKaluga, 248007, Russia
Completed
Research Institute of OncologyRostov-on-Don, 344037, Russia
Completed
Clinical Oncological Dispensary of Omsk RegionOmsk, 644013, Russia
Completed
Kemerovo Regional Clinical HospitalKemerovo, 650066, Russia
Withdrawn
St James' HospitalDublin, D08NHY1, Ireland
Completed
Phramongkutklao HospitalBangkok, 10400, Thailand
Completed
Siriraj Hospital, MahidolBangkok, 10700, Thailand
Completed
Hospital General de México SSMéxico, D. F., 6726, Mexico
Withdrawn
Instituto Nacional de CancerologíaMéxico, 14080, Mexico
Completed
PRATIA MCM KRAKÓWKrakow, 30-727, Poland
Completed
Szpital Morski im. PCKGdynia, 81-519, Poland
Withdrawn
Centrum Onkologii Ziemi Lubelskiej im. Sw. Jana z DukliLublin, 20-090, Poland
Completed
SC ONCO CARD SRLBrasov, 500152, Romania
Withdrawn
Sp. Univ. de Urgenta Militar Central Dr. Carol DavilaBucuresti, 10825, Romania
Completed
Sp. Judetean de Urgenta Dr. Constantin Opris Baia MareBaia Mare, 430031, Romania
Withdrawn
Institutul Oncologic Prof. Dr. Ion ChiricutaCluj-Napoca, 400124, Romania
Completed
Fundeni Clinical InstituteBucuresti, 22328, Romania
Completed
Spitalul Clinic ColentinaBucuresti, 20125, Romania
Completed
Spitalul Clinic ColteaBucuresti, 30171, Romania
Withdrawn
Spitalul Clinic Judetean de Urgenta Targu-MuresTargu Mures, 540136, Romania
Completed
Institutul Regional de Oncologie IasiIasi, 700483, Romania
Completed
Spitalul Clinic Municipal Filantropia CraiovaCraiova, 200143, Romania
Withdrawn
Henry Ford Health SystemDetroit, 48202, United States
Completed
Centre Hospitalier Intercommunal de la Côte Basque-BayonneBAYONNE, 64100, France
Completed
Centro de Investigación Clínica Chapultepec S.A. de C.V.Morelia, 58260, Mexico
Completed
Lewis Hall Singletary Oncology CenterThomasville, 31792, United States
Withdrawn
Tangdu Hospital, the 4th Military Medical University of PLAXian, 710000, China
Completed
Chaim Sheba Medical CenterRamat Gan, 5262000, Israel
Withdrawn
Shanghai East Hospital Affiated to Tongji Universityshanghai, 200100, China
Completed
IEP São LucasSão Paulo, 01234-030, Brazil
Completed
Hospital das Clínicas da Faculdade de Medicina da USPSao Paulo, 05403-000, Brazil
Completed
Faculdade de Ciencias Medicas-Universidade Estadual CampinasCampinas, 130839 970, Brazil
Withdrawn
Hanoi, Viet Nam
Withdrawn
Ho Chi Minh City, Viet Nam
Completed
Centre Hospitalier Universitaire - AngersAngers, 49933, France
Completed
Sun Yat-sen University Cancer CenterGuangzhou, 510000, China
Withdrawn
Ho Chi Minh City, Viet Nam
Withdrawn
Pacific Shores Medical GroupLong Beach, 90813, United States
Withdrawn
Japanese RedCross Aichi Medical Center Nagoya Daini HospitalNagoya, 466-8650, Japan
Completed
National Hospital Organization Kyushu Cancer CenterFukuoka, 811-1395, Japan
Completed
Aichi Cancer Center HospitalNagoya, 464-8681, Japan
Completed
Gunma University HospitalMaebashi, 371-8511, Japan
Withdrawn
Niigata Cancer Center HospitalNiigata, 951-8566, Japan
Withdrawn
Jichi Medical University HospitalShimotsuke, 329-0498, Japan
Withdrawn
Toranomon HospitalMinato-ku, 105-8470, Japan
Completed
Osaka Metropolitan University HospitalOsaka, 545-8586, Japan
Withdrawn
Shimane University HospitalIzumo, 693-8501, Japan
Completed
Yamagata University HospitalYamagata, 990-9585, Japan
Completed
Hyogo Cancer CenterAkashi, 673-8558, Japan
Completed
Aomori Prefectural Central HospitalAomori, 030-8553, Japan
Withdrawn
Shinshu University HospitalMatsumoto, 390-8621, Japan
Completed
National Hospital Organization Kumamoto Medical CenterKumamoto, 860-0008, Japan
Completed
Szabolcs-Szatmar-Bereg Varmegyei OktatokorhazNyiregyhaza, 4400, Hungary
Withdrawn
Univ.of California-San Diego Moores Cancer CenterLa Jolla, 92093-0698, United States
Completed
Clinique Saint AnneSTRASBOURG, 67000, France
Completed
Marienhospital Herne UniversitätsklinikHerne, 44625, Germany
Withdrawn
Valley Hospital Bolger Medical Arts BuildingWestwood, 7675, United States
Withdrawn
St. Luke's Mountain States Tumor Institute - BoiseBoise, 83712, United States
Withdrawn
DBA-Envision Cancer Care, LLCSan Antonio, 78235, United States
Completed
Brian J. LeBerthon, MDWest Covina, 91790, United States
Completed
Constantiaberg Medi ClinicCape Town, 7800, South Africa
Withdrawn
Loyola University Medical CenterMaywood, 60153, United States
Completed
Sociedad de Investigaciones Medicas LtdaTemuco, 4810469, Chile
Withdrawn
Vista Oncology Inc PSOlympia, 98506, United States
Completed
New York Cancer and Blood SpecialistsPort Jefferson Station, 11776, United States
Completed
Ironwood Physicians P.C. DBA Ironwood Cancer & Res. Ctr.Chandler, 85224, United States
Withdrawn
Grand Hôpital de CharleroiGILLY, 6060, Belgium
Withdrawn
Southwest Oklahoma Cancer ResearchLawton, 73505, United States
Withdrawn
Department of OncologyPietermaritzburg, 3201, South Africa
Completed
SCL Health Research at St Joseph's Hospital Denver CODenver, 80218, United States
Completed
Centro Especializado en Investigación Clínica S.C.Boca del Río, 94290, Mexico
Completed
Centro de Atencion e Investigacion Clinica en Oncologia SCPMerida, 97134, Mexico
Completed
Medizinische Hochschule Hannover (MHH)Hannover, 30625, Germany
Completed
Ciutat Sanitaria i Universitaria de la Vall d'HebronBarcelona, 08035, Spain
Withdrawn
MVZ Praxis Pihusch GbRRosenheim, 83022, Germany
Completed
Oncology ConsultantsHouston, 77024-2645, United States
Withdrawn
Detroit Clinical Research CenterFarmington Hills, 48334, United States
Withdrawn
Manchester Royal InfirmaryManchester, M13 9WL, United Kingdom
Completed
Irmandade da Santa Casa de Misericordia de Porto Alegre | Hospital Sao Francisco - Centro Medico Pesquisa Clinica CardiologiaPorto Alegre, 90020-090, Brazil
Withdrawn
Morristown Memorial HospitalMorristown, 07962-1956, United States
Withdrawn
NYU Langone Medical CenterBrooklyn, 11220, United States
Withdrawn
University Health SystemLubbock, 79415, United States
Completed
Hospital Universitario "José Eleuterio González"Monterrey, TBC, Mexico
Completed
Hopital du Sacre-Coeur de MontrealMontreal, QC H4J 1C5, Canada
Withdrawn
Joe Arrington Cancer Research & Treatment CenterLubbock, 79410, United States
Completed
Texas Oncology- McAllenMcAllen, 78503, United States
Withdrawn
Mid Ohio Oncology/Hematology Inc.Columbus, 43219, United States
Withdrawn
Hematology Oncology Center at Nyack HospitalNyack, 19060, United States
Withdrawn
Mission HospitalAsheville, 28801, United States
Withdrawn
Mid Florida Cancer CentersOrange City, 32763-8316, United States
Withdrawn
AUSL della RomagnaForlì Cesena, 47521, Italy
Withdrawn
Istituto Europeo di Oncologia s.r.lMilano, 20141, Italy
Withdrawn
East Carolina UniversityGreenville, 27834, United States
Completed
Municipal Non-Profit Enterprise "City Clinical Hospital ?4" of the Dnipro City CouncilDnipro, 49102, Ukraine
Withdrawn
Winthrop-University HospitalMineola, United States
Completed
Kindai University HospitalOsakasayama-shi, 589-8511, Japan
Completed
Kumamoto University HospitalKumamoto, 860-8556, Japan
Withdrawn
Kurume University HospitalKurume, 830-0011, Japan
Completed
Saitama Medical University International Medical CenterHidaka, 350-1298, Japan
Completed
JCHO Kyushu HospitalKitakyushu, 806-8501, Japan
Withdrawn
Pindara Private HospitalBenowa, 4217, Australia
Withdrawn
The Queen's Medical CenterHonolulu, 96813, United States
Withdrawn
Memorial Sloan Kettering Cancer Center- MonmouthMiddletown, 7748, United States
Withdrawn
Memorial Sloan Kettering Cancer Center- Basking RidgeBasking Ridge, 07920, United States
Completed
Memorial Sloan Kettering Cancer Center- BergenNew York, 10021, United States
Withdrawn
Memorial Sloan Kettering Cancer Center- CommackCommack, 11725, United States
Withdrawn
Memorial Sloan Kettering- NassauUniondale, 11553, United States
Withdrawn
Memorial Sloan Kettering Cancer Center- WestchesterHarrison, 10604, United States
Withdrawn
University of Texas MD Anderson Cancer CenterHouston, 77030, United States
Completed
Hopital Hotel Dieu - NantesNANTES, 44000, France
Withdrawn
Alexian Brothers Medical CenterElk Grove Village, 60007, United States
Completed
Clinique Victor Hugo - Le MansLE MANS CEDEX 2, 72015, France
Completed
Centre Hospitalier de la Durance - AvignonAVIGNON, 84000, France
Withdrawn
Saitama Medical CenterKawagoe, 350-8550, Japan
Withdrawn
Hopital Saint Antoine - ParisPARIS, 75571, France
Withdrawn
Greenebaum Comprehensive Cancer CenterBaltimore, 21201, United States
Withdrawn
Ruppiner Kliniken GmbHNeuruppin, 16816, Germany
Completed
Hiroshima Red Cross & Atomic-bomb Survivors HospitalHiroshima, 730-8619, Japan
Withdrawn
Shizuoka Cancer CenterSunto, 411-8777, Japan
Completed
Osaka Red Cross HospitalOsaka, 543-8555, Japan
Completed
Kanagawa Cancer CenterYokohama, 241-8515, Japan
Completed
Tenri HospitalTenri, 632-8552, Japan
Completed
Spitalul Clinic Judetean de Urgenta SibiuSibiu, 550245, Romania
Withdrawn
Hospital Samaritano de São Paulo LTDASao Paulo, 01236-000, Brazil
Withdrawn
John B. Amos Cancer CenterColumbus, 31904, United States

Primary Outcome

  • SRI: Occurrence of dose-limiting toxicities (DLT)
    Dose-limiting toxicity is defined as any of the following occurring during Cycle 1 at a given dose level and regarded by the investigator and/or the sponsor to be possibly, probably, or definitely related to copanlisib given in combination with R-B or R-CHOP. General: any grade 5 hematologic or non-hematologic toxicity or any delay of >2 weeks of Cycle 2 due to study treatment-related toxicity; Non-hematologic DLT: any non-hematologic toxicity grade ≥ 3; Hematologic DLT: grade 4 absolute neutrophil count decrease lasting >7 days, or grade 4 febrile neutropenia, or grade 4 platelet count decreased or grade 3 platelet count decreased with serious bleeding, or signs of serious bleeding and/or international normalized ratio (INR) increased or partial thromboplastin time (PTT) prolonged of grade 3.
    date_rangeTime Frame:
    At Cycle 1: 28 days for Copa+R-B or 21 days for Copa+R-CHOP
  • Phase 3: Progression-free survival (PFS) by independent central review
    PFS is defined as the time from randomization to progressive disease (PD) or death from any cause (if no progression is documented).
    date_rangeTime Frame:
    Approximately 6 years 4 months

Secondary Outcome

  • SRI: Best overall response
    Best overall response is defined as the best response achieved during the treatment and active follow-up periods; prior to end of study or start of new anti-tumor treatment, whichever occurs first.
    date_rangeTime Frame:
    Approximately 7 years 8 months
  • SRI: Number of subjects with treatment-emergent adverse event (TEAE)
    A treatment-emergent AE is defined as any event arising or worsening after start of study drug administration until 30 days after the last study drug intake.
    date_rangeTime Frame:
    Approximately 4 years 10 months
  • Phase 3: Objective tumor response rate (ORR)-Independent central review
    ORR, as assessed by independent central review, is defined as the percentage of participants who had a best response rating of CR or PR according to the Lugano classification and for subjects with LPL/WM, a response rating of CR, VGPR, PR, or MR according to the Owen criteria, over the whole duration of the study (i.e., until time of analysis of PFS).
    date_rangeTime Frame:
    Up to 6 years 4 months
  • Phase 3: ORR-Investigator assessment
    ORR, as assessed by investigator, is defined as the percentage of participants who had a best response rating of CR or PR according to the Lugano classification and for subjects with LPL/WM, a response rating of CR, VGPR, PR, or MR according to the Owen criteria, over the whole duration of the study (i.e., until time of analysis of PFS).
    date_rangeTime Frame:
    Up to 6 years 4 months
  • Phase 3: Duration of tumor response (DOR)-Independent central review
    DOR, as assessed by independent central review, is defined as the time (in days) from first observed tumor response (CR, VGPR, PR, or MR) until progression or death from any cause, whichever occurred earlier. The DOR was only defined for patients with at least 1 CR, VGPR, PR, or MR.
    date_rangeTime Frame:
    Approximately 6 years 4 months
  • Phase 3: DOR-Investigator assessment
    DOR, as assessed by investigator, is defined as the time (in days) from first observed tumor response (CR, VGPR, PR, or MR) until progression or death from any cause, whichever occurred earlier. The DOR was only defined for patients with at least 1 CR, VGPR, PR, or MR.
    date_rangeTime Frame:
    Approximately 6 years 4 months
  • Phase 3: Complete tumor response rate (CRR)-Independent central review
    CRR, as assessed by independent central review, is defined as the proportion of patients who had a best response rating of CR according to the Lugano classification, and for patients with LPL/WM, a response rating of CR according to the Owen criteria, over the whole duration of the study (i.e., until the time of analysis of PFS).
    date_rangeTime Frame:
    Approximately 6 years 4 months
  • Phase 3: CRR-Investigator assessment
    CRR, as assessed by investigator, is defined as the proportion of patients who had a best response rating of CR according to the Lugano classification, and for patients with LPL/WM, a response rating of CR according to the Owen criteria, over the whole duration of the study (i.e., until the time of analysis of PFS).
    date_rangeTime Frame:
    Approximately 6 years 4 months
  • Phase 3: Disease control rate (DCR)-Independent central review
    DCR, as assessed by independent central review, is defined as the proportion of patients who had a best response rating of CR, VGPR, PR, MR, or stable disease (excluding unconfirmed early stable disease).
    date_rangeTime Frame:
    Approximately 6 years 4 months
  • Phase 3: DCR-Investigator assessment
    DCR, as assessed by investigator, is defined as the proportion of patients who had a best response rating of CR, VGPR, PR, MR, or stable disease (excluding unconfirmed early stable disease).
    date_rangeTime Frame:
    Approximately 6 years 4 months
  • Phase 3: Time to tumor progression (TTP)-Independent central review
    TTP, as assessed by independent central review, is defined as the time from randomization to progression or death related to progression, whichever occurred earlier. Death related to progression was any death except for: death due to an AE unrelated to progression; or death with a specification of “other” as reason (which excludes PD).
    date_rangeTime Frame:
    Approximately 6 years 4 months
  • Phase 3: TTP-Investigator assessment
    TTP, as assessed by investigator, is defined as the time from randomization to progression or death related to progression, whichever occurred earlier. Death related to progression was any death except for: death due to an AE unrelated to progression; or death with a specification of “other” as reason (which excludes PD).
    date_rangeTime Frame:
    Approximately 6 years 4 months
  • Phase 3: Time to next anti-lymphoma treatment (TTNT)
    A new anti-lymphoma therapy is any new systemic anticancer treatment or radiotherapy for lymphoma, with a consolidation intent. TTNT was defined as the time from the date of randomization to the start of new anti-lymphoma therapy, where the date of randomization was considered Day 1. '99999' denotes value could not be estimated due to censored data
    date_rangeTime Frame:
    Approximately 6 years 4 months
  • Phase 3: Overall survival (OS)
    Overall survival is defined as the time from randomization until death from any cause. The OS for patients alive at the time of the database cut-off date was censored to the last date they were known to be alive. Deaths that occurred after the database cut-off date, reported during data cleaning, were considered for establishing the last known alive date at data cut-off. '99999' denotes value could not be estimated due to censored data.
    date_rangeTime Frame:
    Approximately 6 years 4 months
  • Phase 3: time to deterioration in disease-related symptoms-physical (DRS-P) of at least 3 points of lymphoma
    Time to deterioration in DRS-P of at least 3 points, as measured by the FLymSI-18 questionnaire, was evaluated in all patients. It is defined as the time from randomization to DRS-P decline, progression, or death from any reason, whichever occurred earlier.
    date_rangeTime Frame:
    Approximately 6 years 4 months
  • Phase 3: time to improvement in disease-related symptoms-physical (DRS-P) of at least 3 points of lymphoma
    Time to improvement in DRS-P of at least 3 points, as measured by the FLymSI-18 questionnaire, was evaluated for all patients. It is defined as the time from randomization to DRS-P improvement of at least 3 points.
    date_rangeTime Frame:
    Approximately 6 years 4 months
  • Phase 3: Number of subjects with treatment-emergent adverse event (TEAE)
    A treatment-emergent AE is defined as any event arising or worsening after start of study drug administration until 30 days after the last study drug intake.
    date_rangeTime Frame:
    Approximately 4 years

Trial design

A Phase III, randomized, double-blind, controlled multicenter study of intravenous PI3K inhibitor copanlisib in combination with standard immunochemotherapy versus standard immunochemotherapy in patients with relapsed indolent non-Hodgkin’s lymphoma (iNHL)
Trial Type
Interventional
Intervention Type
Drug
Trial Purpose
Treatment
Allocation
Randomized
Blinding
Double Blind
Assignment
Parallel Assignment
Trial Arms
2