Trial Condition(s):

Lymphoma,Non-Hodgkin

Copanlisib and rituximab in relapsed indolent B-cell non-Hodgkin’s lymphoma (iNHL) (CHRONOS-3)

Bayer Identifier:

17067

ClinicalTrials.gov Identifier:

NCT02367040

EudraCT Number:

2013-003893-29

Recruitment Complete

Trial Purpose

The purpose of this study was to evaluate whether copanlisib in combination with rituximab is superior to placebo in combination with rituximab in prolonging progression free survival (PFS) in patients with relapsed iNHL who have received one or more lines of treatment, including rituximab and who either had a treatment-free interval of ≥ 12 months after completion of the last rituximab-containing treatment, or who are unwilling to receive chemotherapy/for whom chemotherapy is contraindicated on reason of age, comorbidities, and/or residual toxicity.

Inclusion Criteria
- Histologically confirmed diagnosis of  Indolent non-Hodgkin’s lymphoma (iNHL) in CD20 positive patients, with histological subtype limited to:
 -- Follicular lymphoma(FL) grade1-2-3a
 -- Small lymphocytic lymphoma(SLL) with absolute lymphocyte count <5x10*9/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) after the last rituximab-, rituximab biosimilars-, or anti-CD20 monoclonal antibody (e.g. obinutuzumab)-containing therapy (other previous treatment lines after rituximab are allowed). A previous regimen is defined as one of the following: at least 2 months of single-agent therapy (less than 2 months of therapy is allowed for patients who responded to single-agent rituximab, rituximab biosimilars, or anti-CD20 monoclonal antibody); at least 2 consecutive cycles of polychemotherapy; autologous transplant; radioimmunotherapy. Previous exposure to PI3K is acceptable (except to copanlisib) provided there is no resistance. Patients with prior intolerance to PI3K inhibitors other than copanlisib are eligible.
 - Non-WM must have at least one bi-dimensionally measurable lesion (which has not been previously irradiated) according to the Lugano Classification. For patients with splenic MZL (Marginal-zone lymphoma) 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 (ULN) 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 for central pathology(obtained within 5 years of the consent date) at Screening
 - Adequate baseline laboratory values collected no more than 7 days before starting study treatment 
 - Left ventricular ejection fraction ≥ 45% 
 - Patients must either:
-- have had a progression-free and treatment-free interval of at least 12 months after completion of the rituximab-, rituximab biosimilars-, or anti-CD20 monoclonal
antibody-containing treatment OR
-- be considered unfit to receive chemotherapy on reason of age, concomitant morbidities, and/or residual toxicity from previous treatments, or unwillingness to receive chemotherapy. These patients must also have had a progression-free and treatment-free interval of at least 6 months after completion of the last rituximab-,
rituximab biosimilars-, or anti-CD20 monoclonal antibody-containing treatment. Patients in whom chemotherapy is contraindicated are defined by one of the following features:
--- Age ≥ 80 years
--- Age < 80 years and at least 1 of the following conditions:
---- at least 3 grade 3 CIRS-G comorbidities OR
---- at least 1 grade 4 CIRS-G comorbidity (if compatible to participation
in the study).
Exclusion Criteria
- Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed disease, or chronic lymphocytic leukemia
 - Progression free interval or treatment free interval of less than 12 months since the last rituximab-, rituximab biosimilars-, or anti-CD20 monoclonal antibody (e.g. obinutuzumab)-containing treatment(including maintenance with these drugs). For patients considered unwilling/unfit to receive chemotherapy : progression free interval or treatment free interval of less than 6 months since the last rituximab-, rituximab biosimilars-, or anti-CD20 monoclonal antibody-containing treatment (including maintenance with these drugs), as assessed by the investigator  
 - History or concurrent condition of interstitial lung disease  of any severity and/or severely impaired lung function
 - Known lymphomatous involvement of the central nervous system
 - Patients with HbA1c > 8.5% at Screening 
 - Known history of human immunodeficiency virus (HIV) infection
 - Hepatitis B (HBV) or hepatitis C (HCV). Patients positive for HBsAg or HBcAb will be eligible if they are negative for HBV-DNA, these patients should receive prophylactic antiviral therapy. Patients positive for anti- HCV antibody will be eligible if they are negative for HCV-RNA
- Documented evidence of resistance to prior treatment with idelalisib or other PI3K inhibitors.
- Prior treatment with copanlisib
- Cytomegalovirus (CMV) infection. Patients who are CMV PCR positive at baseline will not be eligible.

Trial Summary

Enrollment Goal
458
Trial Dates
black-arrow
Phase
3
Could I receive a placebo?
Yes
Products
Copanlisib + Rituximab (BAY80-6946)
Accepts Healthy Volunteers
No

Where to Participate

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Locations
Status
LocationsStatus
Locations

Investigative Site

George, South Africa, 6530

Status
Completed
 
Locations

Investigative Site

Johannesburg, South Africa, 2013

Status
Active, not recruiting
 
Locations

Investigative Site

Singapore, Singapore, 169608

Status
Active, not recruiting
 
Locations

Investigative Site

Singapore, Singapore, 169610

Status
Active, not recruiting
 
Locations

Investigative Site

PESSAC, France, 33600

Status
Completed
 
Locations

Investigative Site

Genova, Italy, 16132

Status
Completed
 
Locations

Investigative Site

Firenze, Italy, 50141

Status
Completed
 
Locations

Investigative Site

Milano, Italy, 20133

Status
Completed
 
Locations

Investigative Site

Ballarat, Australia, 3350

Status
Active, not recruiting
 
Locations

Investigative Site

Ankara, Turkey, 06100

Status
Active, not recruiting
 
Locations

Investigative Site

Izmir, Turkey, 35100

Status
Active, not recruiting
 
Locations

Investigative Site

Istanbul, Turkey, 34093

Status
Active, not recruiting
 
Locations

Investigative Site

Trabzon, Turkey, 61080

Status
Active, not recruiting
 
Locations

Investigative Site

Kayseri, Turkey, 38039

Status
Active, not recruiting
 
Locations

Investigative Site

Seoul, South Korea, 03080

Status
Completed
 
Locations

Investigative Site

Seoul, South Korea, 03722

Status
Active, not recruiting
 
Locations

Investigative Site

Seoul, South Korea, 06351

Status
Completed
 
Locations

Investigative Site

Seoul, South Korea, 05505

Status
Active, not recruiting
 
Locations

Investigative Site

Medellín, Colombia, 050034

Status
Completed
 
Locations

Investigative Site

Bogotá, Colombia, 111511

Status
Active, not recruiting
 
Locations

Investigative Site

Omsk, Russia, 644013

Status
Active, not recruiting
 
Locations

Investigative Site

Kemerovo, Russia, 650066

Status
Active, not recruiting
 
Locations

Investigative Site

Volgograd, Russia, 400138

Status
Active, not recruiting
 
Locations

Investigative Site

Dnipro, Ukraine, 49102

Status
Active, not recruiting
 
Locations

Investigative Site

Canton, United States, 44718

Status
Active, not recruiting
 
Locations

Investigative Site

Krakow, Poland, 30-510

Status
Active, not recruiting
 
Locations

Investigative Site

Gdynia, Poland, 81-519

Status
Active, not recruiting
 
Locations

Investigative Site

Temuco, Chile, 4800827

Status
Active, not recruiting
 
Locations

Investigative Site

Budapest, Hungary, 1088

Status
Active, not recruiting
 
Locations

Investigative Site

Pecs, Hungary, 7624

Status
Completed
 
Locations

Investigative Site

Lviv, Ukraine, 79044

Status
Active, not recruiting
 
Locations

Investigative Site

Cherkasy, Ukraine, 18009

Status
Active, not recruiting
 
Locations

Investigative Site

Vinnitsa, Ukraine, 21029

Status
Completed
 
Locations

Investigative Site

Kiev, Ukraine, 03022

Status
Active, not recruiting
 
Locations

Investigative Site

Kaunas, Lithuania, LT-50009

Status
Completed
 
Locations

Investigative Site

Pathumthani, Thailand, 10120

Status
Completed
 
Locations

Investigative Site

New York, United States, 10021

Status
Active, not recruiting
 
Locations

Investigative Site

Chiang Mai, Thailand, 50200

Status
Active, not recruiting
 
Locations

Investigative Site

Dublin, Ireland, D08 NHY1

Status
Active, not recruiting
 
Locations

Investigative Site

Galway, Ireland, H91 YR71

Status
Active, not recruiting
 
Locations

Investigative Site

Dublin, Ireland, D07 R2WY

Status
Completed
 
Locations

Investigative Site

Sao Paulo, Brazil, 05651-901

Status
Active, not recruiting
 
Locations

Investigative Site

Passo Fundo, Brazil, 99020-240

Status
Completed
 
Locations

Investigative Site

OTTIGNIES, Belgium, 1340

Status
Completed
 
Locations

Investigative Site

Taipei, Taiwan, China, 100

Status
Active, not recruiting
 
Locations

Investigative Site

Taipei, Taiwan, China, 11217

Status
Active, not recruiting
 
Locations

Investigative Site

Changhua, Taiwan, China, 50006

Status
Completed
 
Locations

Investigative Site

Porto, Portugal, 4200-072

Status
Completed
 
Locations

Investigative Site

Vila Nova de Gaia, Portugal, 4434-502

Status
Active, not recruiting
 
Locations

Investigative Site

Singapore, Singapore, 119228

Status
Completed
 
Locations

Investigative Site

Buenos Aires, Argentina, C1431FWO

Status
Completed
 
Locations

Investigative Site

Recklinghausen, Germany, 45659

Status
Completed
 
Locations

Investigative Site

München, Germany, 81377

Status
Active, not recruiting
 
Locations

Investigative Site

Berlin, Germany, 10967

Status
Completed
 
Locations

Investigative Site

Kaposvar, Hungary, 7400

Status
Active, not recruiting
 
Locations

Investigative Site

Majadahonda, Spain, 28222

Status
Active, not recruiting
 
Locations

Investigative Site

Barcelona, Spain, 08041

Status
Completed
 
Locations

Investigative Site

Tatabanya, Hungary, 2800

Status
Completed
 
Locations

Investigative Site

Barcelona, Spain, 08003

Status
Active, not recruiting
 
Locations

Investigative Site

Salamanca, Spain, 37007

Status
Completed
 
Locations

Investigative Site

Barcelona, Spain, 08023

Status
Completed
 
Locations

Investigative Site

Plovdiv, Bulgaria, 4002

Status
Active, not recruiting
 
Locations

Investigative Site

Varna, Bulgaria, 9010

Status
Completed
 
Locations

Investigative Site

Plovdiv, Bulgaria, 4002

Status
Terminated
 
Locations

Investigative Site

NICE Cedex 2, France, 06189

Status
Active, not recruiting
 
Locations

Investigative Site

BAYONNE, France, 64100

Status
Completed
 
Locations

Investigative Site

NANTES, France, 44805

Status
Completed
 
Locations

Investigative Site

BREST, France, 29470

Status
Active, not recruiting
 
Locations

Investigative Site

POITIERS, France, 86021

Status
Active, not recruiting
 
Locations

Investigative Site

Ha Noi, Vietnam, 10000

Status
Completed
 
Locations

Investigative Site

Ho Chi Minh City, Vietnam, 70000

Status
Completed
 
Locations

Investigative Site

Porto Alegre, Brazil, 90880-480

Status
Active, not recruiting
 
Locations

Investigative Site

São Paulo, Brazil, 01236-030

Status
Completed
 
Locations

Investigative Site

São Paulo, Brazil, 05403-000.

Status
Active, not recruiting
 
Locations

Investigative Site

Jaú, Brazil, 17210-120

Status
Completed
 
Locations

Investigative Site

Barretos, Brazil, 14784-400

Status
Completed
 
Locations

Investigative Site

Salt Lake City, United States, 84106

Status
Completed
 
Locations

Investigative Site

Louisville, United States, 40207

Status
Active, not recruiting
 
Locations

Investigative Site

Pasig City, Philippines, 1600

Status
Completed
 
Locations

Investigative Site

Quezon City, Philippines, 1112

Status
Completed
 
Locations

Investigative Site

Athens, Greece, 115 26

Status
Completed
 
Locations

Investigative Site

Chaidari, Greece, 12462

Status
Active, not recruiting
 
Locations

Investigative Site

Athens, Greece, 106 76

Status
Completed
 
Locations

Investigative Site

Monterrey, Mexico, 64460

Status
Active, not recruiting
 
Locations

Investigative Site

Udine, Italy, 33100

Status
Completed
 
Locations

Investigative Site

Graz, Austria, 8036

Status
Completed
 
Locations

Investigative Site

Tauranga, New Zealand, 3112

Status
Completed
 
Locations

Investigative Site

Kazan, Russia, 420029

Status
Active, not recruiting
 
Locations

Investigative Site

Shatin, Hong Kong, China

Status
Active, not recruiting
 
Locations

Investigative Site

Hong Kong, Hong Kong, China

Status
Completed
 
Locations

Investigative Site

Kirov, Russia, 610027

Status
Active, not recruiting
 
Locations

Investigative Site

Córdoba, Argentina, X5000AOQ

Status
Completed
 
Locations

Investigative Site

São Paulo, Brazil, 08270-120

Status
Active, not recruiting
 
Locations

Investigative Site

METZ CEDEX 03, France, 57085

Status
Completed
 
Locations

Investigative Site

Chai Wan, Hong Kong, China

Status
Active, not recruiting
 
Locations

Investigative Site

Dresden, Germany, 01307

Status
Completed
 
Locations

Investigative Site

Halle, Germany, 06120

Status
Completed
 
Locations

Investigative Site

Sofia, Bulgaria, 1756

Status
Completed
 
Locations

Investigative Site

Patras, Greece, 26500

Status
Active, not recruiting
 
Locations

Investigative Site

Jeollanam-do, South Korea, 58128

Status
Completed
 
Locations

Investigative Site

Beijing, China, 100021

Status
Active, not recruiting
 
Locations

Investigative Site

Tianjin, China, 300121

Status
Active, not recruiting
 
Locations

Investigative Site

Shanghai, China, 200030

Status
Active, not recruiting
 
Locations

Investigative Site

Nanjing, China, 210009

Status
Active, not recruiting
 
Locations

Investigative Site

Hangzhou, China, 310003

Status
Active, not recruiting
 
Locations

Investigative Site

Tianjin, China, 300000

Status
Active, not recruiting
 
Locations

Investigative Site

Beijing, China, 100050

Status
Active, not recruiting
 
Locations

Investigative Site

Beijing, China, 100083

Status
Completed
 
Locations

Investigative Site

Hangzhou, China, 310022

Status
Completed
 
Locations

Investigative Site

Chengdu, China, 610041

Status
Active, not recruiting
 
Locations

Investigative Site

Shanghai, China, 200025

Status
Completed
 
Locations

Investigative Site

Beijing, China, 100730

Status
Completed
 
Locations

Investigative Site

Wuhan, China, 430079

Status
Active, not recruiting
 
Locations

Investigative Site

Beijing, China, 100071

Status
Completed
 
Locations

Investigative Site

Urumqi, China, 830011

Status
Active, not recruiting
 
Locations

Investigative Site

Guangzhou, China, 510060

Status
Active, not recruiting
 
Locations

Investigative Site

Shengyang, China, 110042

Status
Active, not recruiting
 
Locations

Investigative Site

Changchun, China, 130000

Status
Active, not recruiting
 
Locations

Investigative Site

Nanchang, China, 330029

Status
Completed
 
Locations

Investigative Site

Fuzhou, China, 350001

Status
Active, not recruiting
 
Locations

Investigative Site

Shanghai, China, 200032

Status
Completed
 
Locations

Investigative Site

Chongqing, China, 400030

Status
Active, not recruiting
 
Locations

Investigative Site

Suzhou, China, 215006

Status
Active, not recruiting
 
Locations

Investigative Site

Nedlands, Australia, 6009

Status
Active, not recruiting
 
Locations

Investigative Site

Gyor, Hungary, 9023

Status
Active, not recruiting
 
Locations

Investigative Site

Málaga, Spain, 29010

Status
Active, not recruiting
 
Locations

Investigative Site

Poprad, Slovakia, 085 01

Status
Active, not recruiting
 
Locations

Investigative Site

Kuala Lumpur, Malaysia, 56000

Status
Completed
 
Locations

Investigative Site

Kuala Lumpur, Malaysia, 59100

Status
Completed
 
Locations

Investigative Site

Kota Kinabalu, Malaysia, 88586

Status
Active, not recruiting
 
Locations

Investigative Site

Madrid, Spain, 28041

Status
Active, not recruiting
 
Locations

Investigative Site

Tainan, Taiwan, China, 704

Status
Completed
 
Locations

Investigative Site

Kaohsiung, Taiwan, China, 833

Status
Active, not recruiting
 
Locations

Investigative Site

Lublin, Poland, 20-090

Status
Active, not recruiting
 
Locations

Investigative Site

St. Petersburg, Russia, 197022

Status
Active, not recruiting
 
Locations

Investigative Site

Montería, Colombia, 230002

Status
Completed
 
Locations

Investigative Site

Perak, Malaysia, 30450

Status
Active, not recruiting
 
Locations

Investigative Site

Spokane, United States, 99208-1129

Status
Active, not recruiting
 
Locations

Investigative Site

Chelyabinsk, Russia, 454048

Status
Completed
 
Locations

Investigative Site

Wien, Austria, 1130

Status
Completed
 
Locations

Investigative Site

Morelia, Mexico, 58260

Status
Completed
 
Locations

Investigative Site

Brasov, Romania, 500152

Status
Active, not recruiting
 
Locations

Investigative Site

Bucuresti, Romania, 010825

Status
Completed
 
Locations

Investigative Site

Cluj-Napoca, Romania, 400015

Status
Completed
 
Locations

Investigative Site

Bucuresti, Romania, 022328

Status
Active, not recruiting
 
Locations

Investigative Site

Bucuresti, Romania, 020125

Status
Active, not recruiting
 
Locations

Investigative Site

Bucharest, Romania, 030171

Status
Active, not recruiting
 
Locations

Investigative Site

Irkutsk, Russia, 664035

Status
Active, not recruiting
 
Locations

Investigative Site

Novosibirsk, Russia, 630087

Status
Completed
 
Locations

Investigative Site

Targu Mures, Romania, 540136

Status
Active, not recruiting
 
Locations

Investigative Site

Craiova, Romania, 200143

Status
Active, not recruiting
 
Locations

Investigative Site

Busan, South Korea, 49241

Status
Completed
 
Locations

Investigative Site

Wien, Austria, 1090

Status
Completed
 
Locations

Investigative Site

Cali, Colombia, 760032

Status
Active, not recruiting
 
Locations

Investigative Site

Busan, South Korea, 49201

Status
Completed
 
Locations

Investigative Site

Selangor, Malaysia, 68000

Status
Active, not recruiting
 
Locations

Investigative Site

Pulau Pinang, Malaysia, 10450

Status
Completed
 
Locations

Investigative Site

Chuo-ku, Japan, 104-0045

Status
Active, not recruiting
 
Locations

Investigative Site

Sendai, Japan, 980-8574

Status
Active, not recruiting
 
Locations

Investigative Site

Kobe, Japan, 650-0047

Status
Active, not recruiting
 
Locations

Investigative Site

Nagoya, Japan, 466-8650

Status
Active, not recruiting
 
Locations

Investigative Site

Fukuoka, Japan, 811-1395

Status
Active, not recruiting
 
Locations

Investigative Site

Nagoya, Japan, 464-8681

Status
Active, not recruiting
 
Locations

Investigative Site

Maebashi, Japan, 371-8511

Status
Active, not recruiting
 
Locations

Investigative Site

Niigata, Japan, 951-8566

Status
Active, not recruiting
 
Locations

Investigative Site

Kurashiki, Japan, 710-8602

Status
Active, not recruiting
 
Locations

Investigative Site

Osaka, Japan, 545-8586

Status
Active, not recruiting
 
Locations

Investigative Site

Izumo, Japan, 693-8501

Status
Active, not recruiting
 
Locations

Investigative Site

Yamagata, Japan, 990-9585

Status
Completed
 
Locations

Investigative Site

Guangzhou, China, 510260

Status
Completed
 
Locations

Investigative Site

Kumamoto, Japan, 860-8556

Status
Completed
 
Locations

Investigative Site

Omura, Japan, 856-8562

Status
Active, not recruiting
 
Locations

Investigative Site

Hirakata, Japan, 573-1191

Status
Active, not recruiting
 
Locations

Investigative Site

Aomori, Japan, 030-8553

Status
Completed
 
Locations

Investigative Site

Nankoku, Japan, 783-8505

Status
Completed
 
Locations

Investigative Site

Chongqing, China, 400042

Status
Completed
 
Locations

Investigative Site

West Covina, United States, 91790

Status
Active, not recruiting
 
Locations

Investigative Site

Las Vegas, United States, 89169

Status
Completed
 
Locations

Investigative Site

Gdansk, Poland, 80-214

Status
Completed
 
Locations

MSK Commack

Long Island, United States

Status
Recruiting
 
Locations

Investigative Site

New York, United States, 10065

Status
Recruiting
 
Locations

MSK Commack

Long Island, United States

Status
Completed
 
Locations

MSK Rockville Centre

Long Island, United States

Status
Completed
 
Locations

MSK Westchester

Harrison, United States

Status
Completed
 
Locations

MSK Basking Ridge

New Jersey, United States

Status
Recruiting
 
Locations

MSK Bergen

New Jersey, United States

Status
Recruiting
 
Locations

MSK Monmoth

New Jersey, United States

Status
Completed
 
Locations

Investigative Site

Ashland, United States, 41101

Status
Completed
 
Locations

Investigative Site

Bethesda, United States, 20817

Status
Active, not recruiting
 
Locations

Investigative Site

Rosario, Argentina, S2000DEJ

Status
Active, not recruiting
 
Locations

Investigative Site

San Miguel de Tucumán, Argentina, T4000

Status
Active, not recruiting
 

Trial Design