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.
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.
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/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%
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
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There are 196 Locations for this study
Chandler Arizona, 85224, United States
West Covina California, 91790, United States
Denver Colorado, 80218, United States
Thomasville Georgia, 31792, United States
New York New York, 10021, United States
New York New York, 10021, United States
Port Jefferson Station New York, 11776, United States
Canton Ohio, 44718, United States
Houston Texas, 77030, United States
McAllen Texas, 78503, United States
Waratah New South Wales, 2298, Australia
Adelaide South Australia, 5042, Australia
Kurralta Park South Australia, 5037, Australia
Prahran Victoria, 3181, Australia
Murdoch Western Australia, 6961, Australia
Box Hill , 3128, Australia
Bruxelles - Brussel , 1000, Belgium
Gent , 9000, Belgium
Leuven , 3000, Belgium
Liege , 4000, Belgium
Curitiba Parana, 80810, Brazil
Porto Alegre Rio Grande Do Sul, 90035, Brazil
Porto Alegre Rio Grande Do Sul, 90050, Brazil
Florianópolis Santa Catarina, 88034, Brazil
Campinas Sao Paulo, 13083, Brazil
Santo Andre Sao Paulo, , Brazil
São Paulo Sao Paulo, 01236, Brazil
São Paulo Sao Paulo, 05403, Brazil
Rio de Janeiro , 20230, Brazil
Sao Paulo , 05651, Brazil
Plovdiv , 4002, Bulgaria
Sofia , 1431, Bulgaria
Sofia , 1756, Bulgaria
Vratsa , 3000, Bulgaria
Montreal Quebec, H1T 2, Canada
Montreal Quebec, QC H4, Canada
Quebec City Quebec, G1J 1, Canada
Sherbrooke Quebec, J1H 5, Canada
Temuco AraucanÃa, 48104, Chile
Vina del Mar ValparaÃso, 25403, Chile
Santiago , 838-0, Chile
Fuzhou Fujian, 35000, China
Guangzhou Guangdong, 51006, China
Guangzhou Guangdong, 51010, China
Shijiazhuang Hebei, 05001, China
Zhengzhou Henan, 45000, China
Nanjing Jiangsu, 21000, China
Suzhou Jiangsu, 21500, China
Changchun Jilin, 13000, China
Qingdao Shandong, 26650, China
Chengdu Sichuan, 61004, China
Hangzhou Zhejiang, 31000, China
Hangzhou Zhejiang, 31002, China
Beijing , 10005, China
Beijing , 10007, China
Shanghai , 20003, China
Shanghai , 20009, China
Tianjin , 30006, China
Tianjin , 30012, China
Hradec Kralove , 50005, Czechia
Praha 10 , 100 3, Czechia
Copenhagen , 2100, Denmark
Odense C , 5000, Denmark
Helsinki , 00290, Finland
Oulu , 90020, Finland
Tampere , 33521, Finland
Turku , 20520, Finland
Angers , 49100, France
Avignon , 84000, France
Bayonne , 64100, France
Grenoble , 38043, France
Le Mans Cedex 2 , 72015, France
Limoges Cedex , 87042, France
Montpellier Cedex , 34295, France
Nantes Cedex , 44093, France
Paris , 75010, France
Pessac , 33600, France
Poitiers , 86021, France
Strasbourg , 67000, France
Mutlangen Baden-Württemberg, 73557, Germany
Augsburg Bayern, 86150, Germany
München Bayern, 81377, Germany
Hannover Niedersachsen, 30625, Germany
Herne Nordrhein-Westfalen, 44625, Germany
Münster Nordrhein-Westfalen, 48149, Germany
Recklinghausen Nordrhein-Westfalen, 45659, Germany
Halle Sachsen-Anhalt, 06120, Germany
Athens , 106 7, Greece
Athens , 115 2, Greece
Chaidari , 12462, Greece
Larissa , 41100, Greece
Patras , 26500, Greece
Shatin , , Hong Kong
Budapest , 1083, Hungary
Budapest , 1088, Hungary
Budapest , 1122, Hungary
Kaposvar , 7400, Hungary
Nyiregyhaza , 4400, Hungary
Pecs , 7624, Hungary
Tatabanya , 2800, Hungary
Cork , , Ireland
Dublin , D07 R, Ireland
Haifa , 31096, Israel
Jerusalem , 91120, Israel
Ramat Gan , 52620, Israel
Zerifin , 60930, Israel
Genova Liguria, 16132, Italy
Milano Lombardia, 20089, Italy
Pavia Lombardia, 27100, Italy
Ancona Marche, 60126, Italy
Nagoya Aichi, 464-8, Japan
Nagoya Aichi, 467-8, Japan
Kitakyushu Fukuoka, 806-8, Japan
Maebashi Gunma, 371-8, Japan
Akashi Hyogo, 673-8, Japan
Kobe Hyogo, 650-0, Japan
Yokohama Kanagawa, 241-8, Japan
Sendai Miyagi, 980-8, Japan
Tenri Nara, 632-8, Japan
Osakasayama Osaka, 589-8, Japan
Hidaka Saitama, 350-1, Japan
Chuo-ku Tokyo, 104-0, Japan
Aomori , 030-8, Japan
Fukuoka , 811-1, Japan
Hiroshima , 730-8, Japan
Kumamoto , 860-0, Japan
Kumamoto , 860-8, Japan
Osaka , 543-8, Japan
Osaka , 545-8, Japan
Yamagata , 990-9, Japan
Seoul , 03722, Korea, Republic of
Seoul , 05505, Korea, Republic of
Seoul , 06351, Korea, Republic of
Seoul , 110-7, Korea, Republic of
Ciudad de México Distrito Federal, 06729, Mexico
Morelia Michoacán, 58260, Mexico
Monterrey Nuevo Leon, 64460, Mexico
Boca del RÃo Veracruz, 94290, Mexico
Merida Yucatán, 97134, Mexico
Gdynia , 81-51, Poland
Krakow , 30-51, Poland
Lodz , 93-51, Poland
Braga , 4710-, Portugal
Porto , 4099-, Portugal
Porto , 4200-, Portugal
Vila Nova de Gaia , 4434-, Portugal
Baia Mare , 43003, Romania
Brasov , 50015, Romania
Bucharest , 02232, Romania
Bucharest , 03017, Romania
Bucuresti , 02012, Romania
Craiova , 20014, Romania
Iasi , 70011, Romania
Sibiu , 55024, Romania
Kemerovo , 65006, Russian Federation
Omsk , 64401, Russian Federation
Rostov-on-Don , 34403, Russian Federation
Saint-Petersburg , 19102, Russian Federation
Sochi , 35405, Russian Federation
Tomsk , 63405, Russian Federation
Ufa , 45005, Russian Federation
Singapore , 11922, Singapore
Singapore , 16961, Singapore
Singapore , 16985, Singapore
Bratislava , 833 1, Slovakia
George Eastern Cape, 6530, South Africa
Port Elizabeth Eastern Cape, 6045, South Africa
Pretoria Gauteng, 0044, South Africa
Cape Town Western Cape, 7800, South Africa
Badalona Barcelona, 08916, Spain
L'Hospitalet de Llobregat Barcelona, 08907, Spain
Majadahonda Madrid, 28222, Spain
Malaga Málaga, 29010, Spain
Barcelona , 08023, Spain
Zaragoza , 50009, Spain
Changhua , 50006, Taiwan
Kaohsiung , 833, Taiwan
Tainan , 704, Taiwan
Taipei , 10002, Taiwan
Taipei , 11217, Taiwan
Bangkok , 10400, Thailand
Bangkok , 10700, Thailand
Ankara , 06100, Turkey
Edirne , 22030, Turkey
Istanbul , 34093, Turkey
Istanbul , 34899, Turkey
Izmir , 35100, Turkey
Izmir , 35340, Turkey
Kayseri , 38039, Turkey
Samsun , 55139, Turkey
Trabzon , 61080, Turkey
Cherkasy , 18009, Ukraine
Dnipro , 49102, Ukraine
Kiev , 03022, Ukraine
Lviv , 79044, Ukraine
Zaporizhzhya , 69600, Ukraine
Exeter Devon, EX2 5, United Kingdom
Harrow London, HA1 3, United Kingdom
Dorchester , DT1 2, United Kingdom
London , SW17 , United Kingdom
Swansea , SA2 8, United Kingdom
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