Non Hodgkin Lymphoma Clinical Trial

Study of Copanlisib in Combination With Standard Immunochemotherapy in Relapsed Indolent Non-Hodgkin’s Lymphoma (iNHL)

Summary

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.

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Full Description

Patients should be in need of and fit for immunochemotherapy and should not be resistant to rituximab (resistance defined as lack of response or progression within 6 months of the last date of rituximab administration, including rituximab, and/or rituximab biosimilars, and/or anti-CD20 monoclonal antibody).

This study will be composed of two parts: Safety run-in and phase III part. The purpose of the safety run-in part of this study is to assess whether the drug being tested (copanlisib) in combination with standard immunochemotherapy (R-B or R-CHOP) is safe and at what dose level of the study drug (copanlisib - 45mg or 60 mg) patients are able to tolerate the study treatment combination. In addition to finding a safe and tolerable dose level for the phase III part of the study, efficacy will also be evaluated for patients that stay on the study treatment during the safety run-in. The phase III part of the study started with the determined recommended dose of copanlisib of 60 mg in combination with R-B. Combination treatment of copanlisib at the recommended/approved dose of 60 mg with R-B or R-CHOP was completed in April 2021.

A maximum of 24 patients will take part in the safety run-in part of this study. In the phase III part approximately 520 patients will be randomly assigned to blinded treatment arms of copanlisib plus R-B or R-CHOP or placebo plus R-B or R-CHOP. Combination therapy (copanlisib/placebo with R-B or R-CHOP) will be administered for a maximum of 6 cycles (C1-C6). Copanlisib/placebo (study drug) monotherapy will be administered from C7 onwards.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

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> 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%

Exclusion Criteria

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

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 3

Estimated Enrollment:

551

Study ID:

NCT02626455

Recruitment Status:

Active, not recruiting

Sponsor:

Bayer

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There are 195 Locations for this study

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Ironwood Physicians P.C. DBA Ironwood Cancer & Res. Ctr.
Chandler Arizona, 85224, United States
Brian J. LeBerthon, MD
West Covina California, 91790, United States
SCL Health Research at St Joseph's Hospital Denver CO
Denver Colorado, 80218, United States
Lewis Hall Singletary Oncology Center
Thomasville Georgia, 31792, United States
Memorial Sloan Kettering Cancer Center
New York New York, 10021, United States
New York Cancer and Blood Specialists
Port Jefferson Station New York, 11776, United States
Gabrail Cancer Center
Canton Ohio, 44718, United States
Oncology Consultants
Houston Texas, 77030, United States
Texas Oncology- McAllen
McAllen Texas, 78503, United States
Calvary Mater Hospital Newcastle
Waratah New South Wales, 2298, Australia
Flinders Medical Centre
Adelaide South Australia, 5042, Australia
Ashford Cancer Centre Research Pty Ltd
Kurralta Park South Australia, 5037, Australia
The Alfred Hospital
Prahran Victoria, 3181, Australia
Fiona Stanley Hospital
Murdoch Western Australia, 6150, Australia
Eastern Health Integrated Renal Service
Box Hill , 3128, Australia
Institut Jules Bordet/Jules Bordet Instituut
Bruxelles - Brussel , 1000, Belgium
UZ Gent
Gent , 9000, Belgium
UZ Leuven Gasthuisberg
Leuven , 3000, Belgium
CHU de Liège
Liege , 4000, Belgium
Centro Integrado de Oncologia de Curitiba
Curitiba Parana, 80810, Brazil
Irmandade Santa Casa de Misericordia de Porto Alegre
Porto Alegre Rio Grande Do Sul, 90050, Brazil
Hospital de Clínicas de Porto Alegre
Porto Alegre Rio Grande Do Sul, , Brazil
Centro de Pesquisas Oncológicas
Florianópolis Santa Catarina, 88034, Brazil
Faculdade de Ciencias Medicas-Universidade Estadual Campinas
Campinas Sao Paulo, 13083, Brazil
Centro Multidisciplinar de Estudos Clínicos EPP - Ltda.
Santo Andre Sao Paulo, , Brazil
IEP São Lucas
São Paulo Sao Paulo, 01236, Brazil
Hospital das Clínicas da Faculdade de Medicina da USP
São Paulo Sao Paulo, 05403, Brazil
Instituto Nacional do Cancer Jose Alencar Gomes da Silva
Rio de Janeiro , 20230, Brazil
Hospital Israelita Albert Einstein
Sao Paulo , 05651, Brazil
UMHAT Sveti Georgi
Plovdiv , 4002, Bulgaria
University Multiprofile Hosp. for Active Treat. Sveti Ivan
Sofia , 1431, Bulgaria
SHATHD Spec. Hospi. for Active Treatm. of Haematol. Dis. EAD
Sofia , 1756, Bulgaria
Multiprofile Hospital for Active Treatment Hristo Botev AD
Vratsa , 3000, Bulgaria
Hopital du Sacre-Coeur de Montreal
Montreal Quebec, H4J 1, Canada
Recherche soins intensifs, hôpital Maisonneuve-Rosemont
Montréal Quebec, H1T 2, Canada
Hopital de L'Enfant Jesus
Quebec City Quebec, G1J 1, Canada
Centre Universitaire de Sante de l'Estrie
Sherbrooke Quebec, J1H 5, Canada
Sociedad de Investigaciones Medicas Ltda
Temuco Araucanía, 48104, Chile
Centro de Investigaciones Clínicas Vina del Mar Ltda.
Vina del Mar Valparaíso, 25403, Chile
Instituto Nacional del Cáncer
Santiago , 838-0, Chile
FuJian Medical University Union Hospital
Fuzhou Fujian, 35000, China
Sun Yat-sen University Cancer Center
Guangzhou Guangdong, 51006, China
Guangdong Provincial People's Hospital
Guangzhou Guangdong, 51010, China
Tumor Hospital of Hebei Province
Shijiazhuang Hebei, 05001, China
Henan Cancer Hospital
Zhengzhou Henan, 45000, China
Jiangsu Cancer Hospital
Nanjing Jiangsu, 21000, China
1st Affiliated hospital of Soochow University
Suzhou Jiangsu, 21500, China
Jilin Cancer Hospital
Changchun Jilin, 13000, China
The Affiliated Hospital of Qingdao University
Qingdao Shandong, 26650, China
West China Hospital Sichuan University
Chengdu Sichuan, 61004, China
The 1st Affiliated Hospital of Zhejiang University
Hangzhou Zhejiang, 31000, China
Zhejiang Cancer Hospital
Hangzhou Zhejiang, 31002, China
Beijing Friendship Hospital, Capital Medical University
Beijing , 10005, China
Fifth Medical Center, General Hospital of the Chinese People
Beijing , 10007, China
Fudan University Shanghai Cancer Center
Shanghai , 20003, China
Xinhua Hos Affiliated to SH Jiaotong Uni School of Medicine
Shanghai , 20009, China
Tianjin Medical University Cancer Institiute & Hospital
Tianjin , 30006, China
Tianjin Union Medicine Centre (People's Hospital of Tianjin)
Tianjin , 30012, China
Fakultni Nemocnice Hradec Kralove
Hradec Kralove , 50005, Czechia
Fakultni nemocnice Kralovske Vinohrady
Praha 10 , 100 3, Czechia
Rigshospitalet
Copenhagen , 2100, Denmark
Odense OUH, Haematologisk afdeling
Odense C , 5000, Denmark
HUS, Meilahden sairaala
Helsinki , 00290, Finland
Oulun yliopistollinen sairaala
Oulu , 90020, Finland
Tampereen yliopistollinen sairaala, keskussairaala
Tampere , 33521, Finland
Turun yliopistollinen keskussairaala
Turku , 20520, Finland
Centre Hospitalier Universitaire - Angers
Angers , 49100, France
Centre Hospitalier de la Durance - Avignon
Avignon , 84000, France
Centre Hospitalier Intercommunal de la Côte Basque-Bayonne
Bayonne , 64100, France
Centre Hospitalier Universite de Grenoble
Grenoble , 38043, France
Clinique Victor Hugo - Le Mans
Le Mans Cedex 2 , 72015, France
Hôpital Dupuytren
Limoges Cedex , 87042, France
Hôpital Saint-Eloi
Montpellier Cedex , 34295, France
Hopital Hotel Dieu - Nantes
Nantes Cedex , 44093, France
Hôpital Saint Louis
Paris , 75010, France
Centre François Magendie - Pessac
Pessac , 33600, France
Hôpital de la Milétrie
Poitiers , 86021, France
Clinique Saint Anne
Strasbourg , 67000, France
Stauferklinikum Schwäbisch-Gmünd
Mutlangen Baden-Württemberg, 73557, Germany
Gemeinschaftspraxis Dr.Heinrich/ Prof.Bangerter
Augsburg Bayern, 86150, Germany
Klinikum der Universität München Grosshadern
München Bayern, 81377, Germany
Medizinische Hochschule Hannover (MHH)
Hannover Niedersachsen, 30625, Germany
Marienhospital Herne Universitätsklinik
Herne Nordrhein-Westfalen, 44625, Germany
Universitätsklinikum Münster (UKM)
Münster Nordrhein-Westfalen, 48149, Germany
Oncologianova GmbH
Recklinghausen Nordrhein-Westfalen, 45659, Germany
Med. Fakultät der Martin-Luther-Universität Halle-Wittenberg
Halle Sachsen-Anhalt, 06120, Germany
EVANGELISMOS General Hospital of Athens
Athens , 106 7, Greece
LAIKO General Hospital of Athens
Athens , 115 2, Greece
University General Hospital of Athens "ATTIKON"
Chaidari , 12462, Greece
Univ. General Hospital of Larissa
Larissa , 41100, Greece
University General Hospital of Patras
Patras , 26500, Greece
Prince of Wales Hospital Hong Kong
Shatin , , Hong Kong
Semmelweis University
Budapest , 1083, Hungary
Semmelweis University
Budapest , 1088, Hungary
Orszagos Onkologiai Intezet
Budapest , 1122, Hungary
Somogy Megyei Kaposi Mor Oktato Korhaz
Kaposvar , 7400, Hungary
SzSzBMK es EOK Josa Andras Oktatokorhaz
Nyiregyhaza , 4400, Hungary
Pecsi Tudomanyegyetem Klinikai Kozpont
Pecs , 7624, Hungary
Szent Borbala Hospital
Tatabanya , 2800, Hungary
Cork University Hospital
Cork , , Ireland
Mater Misericordiae Hospital
Dublin , D07 R, Ireland
Rambam Health Corporation
Haifa , 31096, Israel
Hadassah Hebrew University Hospital Ein Kerem
Jerusalem , 91120, Israel
Chaim Sheba Medical Center
Ramat Gan , 52620, Israel
Shamir Medical Center (Assaf Harofeh)
Zerifin , 60930, Israel
IRCCS Ospedale Policlinico San Martino
Genova Liguria, 16132, Italy
Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.
Milano Lombardia, 20089, Italy
Fondazione IRCCS Policlinico San Matteo
Pavia Lombardia, 27100, Italy
A.O.U. Ospedali Riuniti "Umberto I - G.M.Lancisi - G.Salesi"
Ancona Marche, 60126, Italy
Aichi Cancer Center Hospital
Nagoya Aichi, 464-8, Japan
Nagoya City University Hospital
Nagoya Aichi, 467-8, Japan
JCHO Kyushu Hospital
Kitakyushu Fukuoka, 806-8, Japan
Gunma University Hospital
Maebashi Gunma, 371-8, Japan
Hyogo Cancer Center
Akashi Hyogo, 673-8, Japan
Kobe University Hospital
Kobe Hyogo, 650-0, Japan
Kanagawa Cancer Center
Yokohama Kanagawa, 241-8, Japan
Tohoku University Hospital
Sendai Miyagi, 980-8, Japan
Tenri Hospital
Tenri Nara, 632-8, Japan
Kindai University Hospital
Osakasayama Osaka, 589-8, Japan
Saitama Medical University International Medical Center
Hidaka Saitama, 350-1, Japan
National Cancer Center Hospital
Chuo-ku Tokyo, 104-0, Japan
Aomori Prefectural Central Hospital
Aomori , 030-8, Japan
National Hospital Organization Kyushu Cancer Center
Fukuoka , 811-1, Japan
Hiroshima Red Cross & Atomic-bomb Survivors Hospital
Hiroshima , 730-8, Japan
National Hospital Organization Kumamoto Medical Center
Kumamoto , 860-0, Japan
Kumamoto University Hospital
Kumamoto , 860-8, Japan
Osaka Red Cross Hospital
Osaka , 543-8, Japan
Osaka Metropolitan University Hospital
Osaka , 545-8, Japan
Yamagata University Hospital
Yamagata , 990-9, Japan
Severance Hospital, Yonsei University Health System
Seoul , 03722, Korea, Republic of
Asan Medical Center
Seoul , 05505, Korea, Republic of
Samsung Medical Center
Seoul , 06351, Korea, Republic of
Seoul National University Hospital
Seoul , 110-7, Korea, Republic of
Hospital General de México SS
Ciudad de México Distrito Federal, 06729, Mexico
Centro de Investigación Clínica Chapultepec S.A. de C.V.
Morelia Michoacán, 58260, Mexico
Hospital Universitario "José Eleuterio González"
Monterrey Nuevo Leon, 64460, Mexico
Centro Especializado en Investigación Clínica S.C.
Boca del Río Veracruz, 94290, Mexico
Centro de Atencion e Investigacion Clinica en Oncologia SCP
Merida Yucatán, 97134, Mexico
Szpital Morski im. PCK
Gdynia , 81-51, Poland
Malopolskie Centrum Medyczne
Krakow , 30-51, Poland
Wojew. Szpital Specjalistyczny im. M. Kopernika
Lodz , 93-51, Poland
Centro Clinico Academico - Braga
Braga , 4710-, Portugal
Centro Hospitalar Universitario do Porto
Porto , 4099-, Portugal
IPO Porto
Porto , 4200-, Portugal
CHVNGE - Hospital Eduardo Santos Silva
Vila Nova de Gaia , 4434-, Portugal
Sp. Judetean de Urgenta Dr. Constantin Opris Baia Mare
Baia Mare , 43003, Romania
S.C. Policlinica de Diagnostic Rapid S.A.
Brasov , 50015, Romania
Fundeni Clinical Institute
Bucharest , 02232, Romania
Spitalul Clinic Coltea
Bucharest , 03017, Romania
Spitalul Clinic Colentina
Bucuresti , 02012, Romania
Spitalul Clinic Municipal Filantropia Craiova
Craiova , 20014, Romania
Institutul Regional de Oncologie Iasi
Iasi , 70011, Romania
Spitalul Clinic Judetean de Urgenta Sibiu
Sibiu , 55024, Romania
Kemerovo Regional Clinical Hospital
Kemerovo , 65006, Russian Federation
Clinical Oncological Dispensary of Omsk Region
Omsk , 64401, Russian Federation
Research Institute of Oncology
Rostov-on-Don , 34403, Russian Federation
RSRI of Hematology and Transfusiology
Saint-Petersburg , 19102, Russian Federation
Oncology Dispensary #2
Sochi , 35405, Russian Federation
Siberian State Medical University
Tomsk , 63405, Russian Federation
Republican Clinical Oncology Dispensary Ufa
Ufa , 45005, Russian Federation
National University Hospital
Singapore , 11922, Singapore
National Cancer Center Singapore
Singapore , 16961, Singapore
Singapore General Hospital
Singapore , 16985, Singapore
Narodny onkologicky ustav
Bratislava , 833 1, Slovakia
Outeniqua Cancercare Oncology Unit
George Eastern Cape, 6530, South Africa
Cancercare Langenhoven
Port Elizabeth Eastern Cape, 6045, South Africa
Albert Alberts Stem Cell Transplant Research Centre
Pretoria Gauteng, 0044, South Africa
Constantiaberg Medi Clinic
Cape Town Western Cape, 7800, South Africa
Institut Català d'Oncologia Badalona
Badalona Barcelona, 08916, Spain
Institut Català d'Oncologia Hospitalet
L'Hospitalet de Llobregat Barcelona, 08907, Spain
Hospital Universitario Clinica Puerta de Hierro
Majadahonda Madrid, 28222, Spain
Hospital Regional de Malaga | Oncologia
Malaga Málaga, 29010, Spain
Ciutat Sanitària i Universitaria de la Vall d'Hebron
Barcelona , 08035, Spain
Hospital Clínico Universitario Lozano Blesa
Zaragoza , 50009, Spain
Changhua Christian Hospital
Changhua , 50006, Taiwan
Chang Gung Memorial Hospital Kaohsiung
Kaohsiung , 833, Taiwan
National Cheng Kung University Hospital
Tainan , 704, Taiwan
National Taiwan University Hospital
Taipei , 10002, Taiwan
Taipei Veterans General Hospital
Taipei , 11217, Taiwan
Pramongkutklao Hospital
Bangkok , 10400, Thailand
Siriraj Hospital, Mahidol
Bangkok , 10700, Thailand
Ankara Universitesi Tip Fakultesi Hastanesi
Ankara , 06100, Turkey
Trakya Univ. Tip Fak.
Edirne , 22030, Turkey
Istanbul Universitesi Istanbul Tip Fakultesi
Istanbul , 34093, Turkey
Marmara Uni. Tip Fakultesi Pendik Egitim ve Aras. Hastanesi
Istanbul , 34899, Turkey
Ege Universitesi Tip Fakultesi
Izmir , 35100, Turkey
Dokuz Eylul Universitesi Tip Fakultesi
Izmir , 35340, Turkey
Erciyes Universitesi Tip Fakultesi
Kayseri , 38039, Turkey
Ondokuz Mayis Uni Tip Fakultesi
Samsun , 55139, Turkey
Karadeniz Teknik Universitesi Tip Fakultesi
Trabzon , 61080, Turkey
Cherkasy Oncological Dispensary
Cherkasy , 18009, Ukraine
Multidisciplinary Clinical Hosp. 4 Dnipro
Dnipro , 49102, Ukraine
National Cancer Institute-Ukraine
Kiev , 03022, Ukraine
Institute of Blood Pathology and Transfusion medicine
Lviv , 79044, Ukraine
Zaporizhzhia Regional Clinical Hospital
Zaporizhzhya , 69600, Ukraine
Royal Devon & Exeter Hospital
Exeter Devon, EX2 5, United Kingdom
Northwick Park Hospital
Harrow London, HA1 3, United Kingdom
Dorset County Hospital
Dorchester , DT1 2, United Kingdom
St. George's Hospital
London , SW17 , United Kingdom
Singleton Hospital
Swansea , SA2 8, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Non Hodgkin Lymphoma

Phase:

Phase 3

Estimated Enrollment:

551

Study ID:

NCT02626455

Recruitment Status:

Active, not recruiting

Sponsor:


Bayer

How clear is this clinincal trial information?

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