AzTrials
AzTrials

Lymphoma,Non-HodgkinPhase 3CHRONOS-3NCT02367040

Copanlisib and Rituximab in Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (iNHL)

A Phase 3 study testing Copanlisib (Aliqopa, BAY80-6946) and Rituximab in people with Lymphoma,Non-Hodgkin, run by Bayer at 187 sites in 37 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma,Non-Hodgkin
What is being tested?
Copanlisib (Aliqopa, BAY80-6946) and Rituximab
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
458 participants
Where
187 sitesin 37 countries
Study dates
3 Aug 2015to 15 Nov 2024
Phase
Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).

Who cannot join

  • 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
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  • 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 locations and contacts

187 sites in 37 countries.

187 sites in 37 countries

China24 sites
  • Study site

    Beijing, 100000

  • Study site

    Beijing, 100050

  • Study site

    Beijing, 100083

  • Study site

    Beijing, 100730

  • Study site

    Changchun, Jilin, 130061

  • Study site

    Chengdu, Sichuan, 610041

  • Study site

    Chongqing, 400030

  • Study site

    Chongqing, 400042

  • Study site

    Fuzhou, Fujian, 350000

  • Study site

    Guangzhou, Guangdong, 510000

  • Study site

    Guangzhou, Guangdong, TBC

  • Study site

    Hangzhou, Zhejiang, 310000

  • Study site

    Hangzhou, Zhejiang, 310022

  • Study site

    Nanchang, Jiangxi, 330029

  • Study site

    Nanjing, Jiangsu, 210000

  • Study site

    Shanghai, 200000

  • Study site

    Shanghai, 200025

  • Study site

    Shanghai, 200032

  • Study site

    Shengyang, Liaoning, 110042

  • Study site

    Suzhou, Jiangsu, 215000

  • Study site

    Tianjin, 300000

  • Study site

    Tianjin, 300121

  • Study site

    Ürümqi, Xinjiang, 830011

  • Study site

    Wuhan, Hubei, 430079

Other trials in China

Japan17 sites
  • Study site

    Aomori, 030-8553

  • Study site

    Chuo-ku, Tokyo, 104-0045

  • Study site

    Fukuoka, 811-1395

  • Study site

    Hirakata, Osaka, 573-1191

  • Study site

    Izumo, Shimane, 693-8501

  • Study site

    Kobe, Hyōgo, 650-0047

  • Study site

    Kumamoto, 860-8556

  • Study site

    Kurashiki, Okayama-ken, 710-8602

  • Study site

    Maebashi, Gunma, 371-8511

  • Study site

    Nagoya, Aichi-ken, 464-8681

  • Study site

    Nagoya, Aichi-ken, 466-8650

  • Study site

    Nankoku, Kochi, 783-8505

  • Study site

    Niigata, 951-8566

  • Study site

    Ōmura, Nagasaki, 856-8562

  • Study site

    Osaka, 545-8586

  • Study site

    Sendai, Miyagi, 980-8574

  • Study site

    Yamagata, 990-9585

Other trials in Japan

United States16 sites
  • Study site

    Ashland, Kentucky, 41101

  • Study site

    Bethesda, Maryland, 20817

  • Study site

    Canton, Ohio, 44718

  • MSK Westchester

    Harrison, New York

  • Study site

    Las Vegas, Nevada, 89169

  • MSK Commack

    Long Island City, New York

  • MSK Rockville Centre

    Long Island City, New York

  • Study site

    Louisville, Kentucky, 40207

  • Study site

    Montvale, New Jersey, 07645

  • MSK Basking Ridge

    New Jersey, New Jersey

  • MSK Bergen

    New Jersey, New Jersey

  • MSK Monmoth

    New Jersey, New Jersey

  • Study site

    New York, New York, 10065

  • Study site

    Salt Lake City, Utah, 84106

  • Study site

    Spokane, Washington, 99208

  • Study site

    West Covina, California, 91790

Other trials in United States

Russia9 sites
  • Study site

    Chelyabinsk, 454048

  • Study site

    Irkutsk, 664035

  • Study site

    Kazan', 420029

  • Study site

    Kemerovo, 650066

  • Study site

    Kirov, 610027

  • Study site

    Novosibirsk, 630087

  • Study site

    Omsk, 644013

  • Study site

    Saint Petersburg, 197022

  • Study site

    Volgograd, 400138

Other trials in Russia

Brazil8 sites
  • Study site

    Barretos/SP, São Paulo, 14784-400

  • Study site

    Jaú, São Paulo, 17210-120

  • Study site

    Passo Fundo, Rio Grande do Sul, 99020-240

  • Study site

    Porto Alegre, Rio Grande do Sul, 90850-170

  • Study site

    São Paulo, São Paulo, 01234-030

  • Study site

    São Paulo, São Paulo, 08270-070

  • Study site

    São Paulo, 05403-000

  • Study site

    São Paulo, 05651-901

Other trials in Brazil

Romania8 sites
  • Study site

    Brasov, 500152

  • Study site

    Bucharest, 10825

  • Study site

    Bucharest, 20125

  • Study site

    Bucharest, 22328

  • Study site

    Bucharest, 30171

  • Study site

    Cluj-Napoca, 400015

  • Study site

    Craiova, 200143

  • Study site

    Târgu Mureş, 540136

Other trials in Romania

France7 sites
  • Study site

    Bayonne, 64100

  • Study site

    Brest, 29470

  • Study site

    Metz, 57085

  • Study site

    Nice, 6189

  • Study site

    Pessac, 33600

  • Study site

    Poitiers, 86021

  • Study site

    Saint-Herblain, 44800

Other trials in France

South Korea7 sites
  • Study site

    Busan, 49201

  • Study site

    Busan, 49241

  • Study site

    Hwasun Gun, 58128

  • Study site

    Seoul, Seoul Teugbyeolsi, 03722

  • Study site

    Seoul, Seoul Teugbyeolsi, 05505

  • Study site

    Seoul, Seoul Teugbyeolsi, 3080

  • Study site

    Seoul, 06351

Other trials in South Korea

Spain7 sites
  • Study site

    Barcelona, 08003

  • Study site

    Barcelona, 08035

  • Study site

    Barcelona, 8041

  • Study site

    Madrid, 28041

  • Study site

    Majadahonda, Madrid, 28222

  • Study site

    Málaga, Málaga, 20910

  • Study site

    Salamanca, 37007

Other trials in Spain

Malaysia6 sites
  • Study site

    Cheras, 56000

  • Study site

    Kota Kinabalu, 88586

  • Study site

    Kuala Lumpur, 59100

  • Study site

    Kuala Selangor, 68000

  • Study site

    Perak, 30450

  • Study site

    Pulau Pinang, 10450

Other trials in Malaysia

Germany5 sites
  • Study site

    Berlin, 10967

  • Study site

    Dresden, Saxony, 1307

  • Study site

    Halle, Saxony-Anhalt, 6120

  • Study site

    München, Bavaria, 81377

  • Study site

    Recklinghausen, North Rhine-Westphalia, 45659

Other trials in Germany

Hungary5 sites
  • Study site

    Budapest, 1083

  • Study site

    Győr, 9024

  • Study site

    Kaposvár, 7400

  • Study site

    Pécs, 7623

  • Study site

    Tatabánya, 2800

Other trials in Hungary

Taiwan5 sites
  • Study site

    Changhua, 50006

  • Study site

    Kaohsiung City, 833

  • Study site

    Tainan, 704

  • Study site

    Taipei, 100

  • Study site

    Taipei, 11217

Other trials in Taiwan

Turkey (Türkiye)5 sites
  • Study site

    Ankara, 6100

  • Study site

    Istanbul, 34093

  • Study site

    Izmir, 35100

  • Study site

    Kayseri, 38039

  • Study site

    Trabzon, 61080

Other trials in Turkey (Türkiye)

Ukraine5 sites
  • Study site

    Cherkasy, 18009

  • Study site

    Dnipro, 49102

  • Study site

    Kyiv, 03022

  • Study site

    Lviv, 79044

  • Study site

    Vinnitsa, 21029

Other trials in Ukraine

Argentina4 sites
  • Study site

    Buenos Aires, Ciudad Auton. de Buenos Aires, TBC

  • Study site

    Córdoba, X5000AOQ

  • Study site

    Rosario, Santa Fe Province, S2000DEJ

  • Study site

    San Miguel de Tucumán, Tucumán Province, T4000

Other trials in Argentina

Colombia4 sites
  • Study site

    Bogota, Cundinamarca, 111511

  • Study site

    Cali, Valle del Cauca Department, 760032

  • Study site

    Medellín, Antioquia, 050034

  • Study site

    Montería, Departamento de Córdoba, 230002

Other trials in Colombia

Greece4 sites
  • Study site

    Athens, 106 76

  • Study site

    Athens, 11527

  • Study site

    Chaïdári, 12462

  • Study site

    Pátrai, 26500

Other trials in Greece

Italy4 sites
  • Study site

    Florence, Tuscany, 50134

  • Study site

    Genoa, Liguria, 16132

  • Study site

    Milan, Lombardy, 20133

  • Study site

    Udine, Friuli Venezia Giulia, 33038

Other trials in Italy

Poland4 sites
  • Study site

    Gdansk, 80-214

  • Study site

    Gdynia, 81-519

  • Study site

    Krakow, 30-727

  • Study site

    Lublin, 20-090

Other trials in Poland

Austria3 sites
  • Study site

    Graz, Styria, 8036

  • Study site

    Vienna, 1090

  • Study site

    Vienna, 1130

Other trials in Austria

Bulgaria3 sites
  • Study site

    Plovdiv, 4000

  • Study site

    Sofia, 1756

  • Study site

    Varna, 9010

Other trials in Bulgaria

Ireland3 sites
  • Study site

    Dublin, D07R2WY

  • Study site

    Dublin, D08NHY1

  • Study site

    Galway, H91YR71

Other trials in Ireland

Singapore3 sites
  • Study site

    Singapore, 119074

  • Study site

    Singapore, 168583

  • Study site

    Singapore, 169608

Other trials in Singapore

Australia2 sites
  • Study site

    Ballarat, Victoria, 3350

  • Study site

    Nedlands, 6009

Other trials in Australia

Hong Kong2 sites
  • Study site

    Chai Wan, 0

  • Study site

    Hong Kong, MISSING

Other trials in Hong Kong

Mexico2 sites
  • Study site

    Monterrey, Nuevo León, 64460

  • Study site

    Morelia, Michoacán, 58260

Other trials in Mexico

Philippines2 sites
  • Study site

    City of Taguig, 1102

  • Study site

    Pasig, 1605

Other trials in Philippines

Portugal2 sites
  • Study site

    Porto, 4200-072

  • Study site

    Porto, 4434-502

Other trials in Portugal

South Africa2 sites
  • Study site

    George, Eastern Cape, 6530

  • Study site

    Johannesburg, Gauteng, 2013

Other trials in South Africa

Thailand2 sites
  • Study site

    Chiang Mai, 50200

  • Study site

    Pathum Thani, 10120

Other trials in Thailand

Vietnam2 sites
  • Study site

    Hà Nội, 10000

  • Study site

    Ho Chi Minh City, 70000

Other trials in Vietnam

Belgium1 site
  • Study site

    Ottignies, 1340

Other trials in Belgium

Chile1 site
  • Study site

    Temuco, Araucania, 4800827

Other trials in Chile

Lithuania1 site
  • Study site

    Kaunas, LT-50009

Other trials in Lithuania

New Zealand1 site
  • Study site

    Tauranga, 3112

Other trials in New Zealand

Slovakia1 site
  • Study site

    Poprad, 058 01

Other trials in Slovakia

About this study

Official title: A Phase III, Randomized, Double-blind, Placebo-controlled Study Evaluating the Efficacy and Safety of Copanlisib in Combination With Rituximab in Patients With Relapsed Indolent B-cell Non-Hodgkin's Lymphoma (iNHL) - CHRONOS-3

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.

Being tested
Copanlisib (Aliqopa, BAY80-6946), Placebo, Rituximab
Keywords
Clinical trial, Phase III, Phosphatidylinositol-3-kinase, Non-Hodgkin's lymphoma, Indolent B-cell non-Hodgkin's lymphoma
Medical subject headings
Lymphoma, Non-Hodgkin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Copanlisib (Aliqopa, BAY80-6946)Drug

    Copanlisib is supplied as lyophilized preparation in a 6 mL injection vial. The total amount of copanlisib per vial is 60 mg. The solution for IV infusions is obtained after reconstitution with normal saline solution. Dosing will be administered on Days 1, 8 and 15 of each 28-day cycle. Copanlisib will be administered before rituximab.

  • PlaceboDrug

    Placebo is supplied as lyophilized preparation in a 6 mL injection vial. The developed placebo lyophilisate is equivalent to the 60 mg copanlisib formulation, with regard to the composition of excipients and the instructions for reconstitution and dose preparation. Placebo dosing will be administered on Days 1, 8 and 15 of each 28-day cycle. Placebo will be administered before rituximab.

  • RituximabDrug

    Rituximab dose 375 mg/m2 body surface weekly during Cycle 1 on Days 1, 8, 15 and 22, and then on Day 1 of Cycles 3, 5, 7 and 9.The solution for IV infusions is obtained after reconstitution of a calculated concentration of 1 to 4 mg/ml rituximab into an infusion bag containing sterile, pyrogen-free sodium chloride 9 mg/ml (0.9%) solution for injection or 5% D-Glucose in water.

Study groups in NCT02367040
Study groupRoleWhat they receive
Copanlisib + RituximabExperimentalCombination of the Copanlisib and rituximab
Receives: Drug: Copanlisib (Aliqopa, BAY80-6946); Drug: Rituximab
Placebo + RituximabPlacebo comparatorCombination of Copanlisib placebo and rituximab
Receives: Drug: Placebo; Drug: Rituximab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression Free Survival (PFS) Based on Independent Central Review.

    Progression-free survival (PFS) was defined as the time from randomization to progressive disease (PD) or death due to any cause, whichever was earlier according to the Lugano Classification and Response criteria in patients affected by Waldenström macroglobulinemia (kindly refer to the links in the Protocol section).

    Measured: From first participant randomization (20-Aug-2015) up to data cut-off at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years and final analysis at 15-Nov-2024 up to 9 years

Secondary outcomes (11)
  1. Objective Response Rate (ORR)

    Objective response rate (ORR) was defined as the percentage of participants who have a best response rating over the whole duration of the study (i.e. until time of analysis of PFS) of complete response (CR) or partial response (PR) according to the Lugano Classification and for patients with Waldenström macroglobulinemia (WM) a response rating of CR, very good partial response (VGPR), PR, or minor response (MR) according to the Owen Criteria (kindly refer to the links in the Protocol section).

    Measured: From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years

  2. Complete Response Rate (CRR)

    Complete response rate (CRR) was defined as the percentage of participants who had a best response rating over the whole duration of the study (i.e., until the time of analysis of PFS) according to the Lugano Classification and for patients with Waldenström macroglobulinemia (WM) a response rating of Complete Response according to the Owen Criteria (kindly refer to the links in the Protocol section).

    Measured: From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years

  3. Duration of Response (DOR)

    Duration of response (DOR) was defined as the time (in days) from first observed tumor response Complete Response (CR), Very good partial response (VGPR), Partial Response (PR) or Minor Response (MR) until progression or death from any cause, whichever occurred earlier according to the Owen Criteria (kindly refer to the links in the Protocol section). Only patients with response in FAS were included in the analysis.

    Measured: From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years

  4. Disease Control Rate (DCR)

    Disease control rate was defined as the percentage of participants who had a best response rating as Complete Response (CR), Partial Response (PR) or stable disease (SD) according to the Lugano Classification and for patients with Waldenström macroglobulinemia (WM) as a response rating of CR, very good partial response (VGPR), PR, minor response (MR) or stable disease (SD) according to the Owen Criteria (kindly refer to the links in the Protocol section).

    Measured: From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years

  5. Time to Progression (TTP)

    Time to progression (TTP) was defined as the time (days) from date of randomization to date of first observed disease progression according to the Lugano Classification and Response criteria in patients affected by Waldenström macroglobulinemia (kindly refer to the links in the Protocol section).

    Measured: From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years

  6. Overall Survival (OS)

    Overall survival was defined as the time (in days) from randomization until death from any cause.

    Measured: From randomization up to the final analysis at 15-Nov-2024 up to 9 years

  7. Time to Deterioration in DRS-P (Disease-Related Symptoms - Physical) of at Least Three Points, as Measured by the Functional Assessment of Cancer Therapy Lymphoma Symptom Index-18 (FLymSI-18) Questionnaire.

    Time to deterioration in DRS-P (Disease-Related Symptoms - Physical) of at least three points was defined as the time (in days) from randomization to DRS-P decline, progression, or death due to any reason, whichever occurred earlier. The Lymphoma Symptom Index-18 (FLymSI-18) questionnaire contains 18 items, each of which utilizes a Likert scale with 5 possible responses ranging from 0 'Not at all' to 4 'Very much' and was divided into a total score.

    Measured: From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years

  8. Time to Improvement in DRS-P (Disease-Related Symptoms - Physical) of at Least 3 Points, as Measured by the Functional Assessment of Cancer Therapy Lymphoma Symptom Index-18 (FLymSI-18) Questionnaire.

    Time to improvement in DRS-P (Disease-Related Symptoms - Physical) was defined as the time (in days) from randomization to DRS-P improvement of at least three points. The Lymphoma Symptom Index-18 (FLymSI-18) questionnaire contains 18 items, each of which utilizes a Likert scale with 5 possible responses ranging from 0 'Not at all' to 4 'Very much' and was divided into a total score.

    Measured: From first participant randomization (20-Aug-2015) up to data cut-off date at primary completion (31-Aug-2020), approximately 5 years and 2-year follow-up after primary completion at 31-Aug-2022, up to 7 years

  9. Number of Participants With Treatment-emergent Adverse Events (TEAEs) at Primary Completion Date.

    Adverse events were considered to be treatment-emergent if they have started or worsened after first application of study medication up to 30 days after end of treatment with study medication.

    Measured: Up to 30 days after end of treatment with study drug, data reporting cut-off at 5 years from the first participant randomization date

  10. Number of Participants With Treatment-emergent Adverse Events (TEAEs) at 2-year Follow-up Cut-off Date.

    Adverse events were considered to be treatment-emergent if they have started or worsened after first application of study medication up to 30 days after end of treatment with study medication.

    Measured: Up to 30 days after end of treatment with study drug, data reporting cut-off at 7 years from the first participant randomization date

  11. Number of Participants With Treatment-emergent Adverse Events (TEAEs) at Final Analysis

    Adverse events were considered to be treatment-emergent if they have started or worsened after first application of study medication up to 30 days after end of treatment with study medication.

    Measured: Up to 30 days after end of treatment with study drug, data reporting cut-off at final analysis, up to 9 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 Feb 2015 (estimated)
  2. Study start3 Aug 2015
  3. Primary completion31 Aug 2020
  4. Study completion15 Nov 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
458 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02367040
Sponsor's protocol ID
17067
Other IDs
2013-003893-29
Acronym
CHRONOS-3
Status last verified
Sep 2025
First submitted
12 Feb 2015
Last updated
14 Oct 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No: Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.vivli.org to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the member section of the portal.

Publications

  • Matasar MJ, Capra M, Ozcan M, Lv F, Li W, Yanez E, Sapunarova K, Lin T, Jin J, Jurczak W, Hamed A, Wang MC, Baker R, Bondarenko I, Zhang Q, Feng J, Geissler K, Lazaroiu M, Saydam G, Szomor A, Bouabdallah K, Galiulin R, Uchida T, Soler LM, Cao A, Hiemeyer F, Mehra A, Childs BH, Shi Y, Zinzani PL. Copanlisib plus rituximab versus placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (CHRONOS-3): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 May;22(5):678-689. doi: 10.1016/S1470-2045(21)00145-5. Epub 2021 Apr 10.

    PubMed 33848462
  • Morcos PN, Moss J, Veasy J, Hiemeyer F, Childs BH, Garmann D. Model-Based Benefit/Risk Analysis for the Copanlisib Intermittent Dosing Regimen. Clin Pharmacol Ther. 2024 May;115(5):1092-1104. doi: 10.1002/cpt.3173. Epub 2024 Jan 16.

    PubMed 38226495

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