Study of Copanlisib in Combination With Standard Immunochemotherapy in Relapsed Indolent Non-Hodgkin's Lymphoma (iNHL) (CHRONOS-4)
Primary Purpose
Lymphoma, Non-Hodgkin
Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Copanlisib (BAY80-6946)
Placebo
Rituximab
Cyclophosphamide
Doxorubicin
Vincristine
Bendamustine
Prednisone
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Non-Hodgkin focused on measuring Clinical trial, Phase III, Phosphatidylinositol-3-kinase, Non-Hodgkin's lymphoma, Indolent B-cell non-Hodgkin's lymphoma
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
Sites / Locations
- Ironwood Physicians P.C. DBA Ironwood Cancer & Res. Ctr.
- Brian J. LeBerthon, MD
- SCL Health Research at St Joseph's Hospital Denver CO
- Lewis Hall Singletary Oncology Center
- Memorial Sloan Kettering Cancer Center
- Memorial Sloan-Kettering Cancer Center
- New York Cancer and Blood Specialists
- Gabrail Cancer Center
- Oncology Consultants
- Texas Oncology- McAllen
- Calvary Mater Hospital Newcastle
- Flinders Medical Centre
- Ashford Cancer Centre Research Pty Ltd
- The Alfred Hospital
- Fiona Stanley Hospital
- Eastern Health Integrated Renal Service
- Institut Jules Bordet/Jules Bordet Instituut
- UZ Gent
- UZ Leuven Gasthuisberg
- CHU de Liège
- Centro Integrado de Oncologia de Curitiba
- Hospital de Clínicas de Porto Alegre
- Irmandade Santa Casa de Misericordia de Porto Alegre
- Centro de Pesquisas Oncológicas
- Faculdade de Ciencias Medicas-Universidade Estadual Campinas
- Centro Multidisciplinar de Estudos Clínicos EPP - Ltda.
- IEP São Lucas
- Hospital das Clínicas da Faculdade de Medicina da USP
- Instituto Nacional do Cancer Jose Alencar Gomes da Silva
- Hospital Israelita Albert Einstein | Morumbi - Clinical Research Department
- UMHAT Sveti Georgi
- University Multiprofile Hosp. for Active Treat. Sveti Ivan
- SHATHD Spec. Hospi. for Active Treatm. of Haematol. Dis. EAD
- Multiprofile Hospital for Active Treatment Hristo Botev AD
- Hopital Maisonneuve-Rosemont
- Hopital du Sacre-Coeur de Montreal
- Hopital de L'Enfant Jesus
- Centre Universitaire de Sante de l'Estrie
- Sociedad de Investigaciones Medicas Ltda
- Centro de Investigaciones Clínicas Vina del Mar Ltda.
- Instituto Nacional del Cáncer
- FuJian Medical University Union Hospital
- Sun Yat-sen University Cancer Center
- Guangdong Provincial People's Hospital
- Tumor Hospital of Hebei Province
- Henan Cancer Hospital
- Jiangsu Cancer Hospital
- 1st Affiliated hospital of Soochow University
- Jilin Cancer Hospital
- The Affiliated Hospital of Qingdao University
- West China Hospital Sichuan University
- The 1st Affiliated Hospital of Zhejiang University
- Zhejiang Cancer Hospital
- Beijing Friendship Hospital, Capital Medical University
- Fifth Medical Center, General Hospital of the Chinese People
- Fudan University Shanghai Cancer Center
- Xinhua Hos Affiliated to SH Jiaotong Uni School of Medicine
- Tianjin Medical University Cancer Institiute & Hospital
- Tianjin Union Medicine Centre (People's Hospital of Tianjin)
- Fakultni Nemocnice Hradec Kralove
- Fakultni nemocnice Kralovske Vinohrady
- Rigshospitalet
- Odense OUH, Haematologisk afdeling
- HUS, Meilahden sairaala
- Oulun yliopistollinen sairaala
- Tampereen yliopistollinen sairaala, keskussairaala
- Turun yliopistollinen keskussairaala
- Centre Hospitalier Universitaire - Angers
- Centre Hospitalier de la Durance - Avignon
- Centre Hospitalier Intercommunal de la Côte Basque-Bayonne
- Centre Hospitalier Universite de Grenoble
- Clinique Victor Hugo - Le Mans
- Hôpital Dupuytren
- Hôpital Saint-Eloi
- Hopital Hotel Dieu - Nantes
- Hôpital Saint Louis
- Centre François Magendie - Pessac
- Hôpital de la Milétrie
- Clinique Saint Anne
- Stauferklinikum Schwäbisch-Gmünd
- Gemeinschaftspraxis Dr.Heinrich/ Prof.Bangerter
- Klinikum der Universität München Grosshadern
- Medizinische Hochschule Hannover (MHH)
- Marienhospital Herne Universitätsklinik
- Universitätsklinikum Münster (UKM)
- Oncologianova GmbH
- Med. Fakultät der Martin-Luther-Universität Halle-Wittenberg
- EVANGELISMOS General Hospital of Athens
- LAIKO General Hospital of Athens
- University General Hospital of Athens "ATTIKON"
- Univ. General Hospital of Larissa
- University General Hospital of Patras
- Prince of Wales Hospital Hong Kong
- Semmelweis University
- Semmelweis University
- Orszagos Onkologiai Intezet
- Somogy Varmegyei Kaposi Mor Oktato Korhaz
- SzSzBMK es EOK Josa Andras Oktatokorhaz
- Pecsi Tudomanyegyetem Klinikai Kozpont
- Komarom-Esztergom Varmegyei Szent Borbala Korhaz
- Cork University Hospital
- Mater Misericordiae Hospital
- Rambam Health Corporation
- Hadassah Hebrew University Hospital Ein Kerem
- Chaim Sheba Medical Center
- Shamir Medical Center (Assaf Harofeh)
- IRCCS Ospedale Policlinico San Martino
- Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.
- Fondazione IRCCS Policlinico San Matteo
- A.O.U. Ospedali Riuniti "Umberto I - G.M.Lancisi - G.Salesi"
- Aichi Cancer Center Hospital
- Nagoya City University Hospital
- JCHO Kyushu Hospital
- Gunma University Hospital
- Hyogo Cancer Center
- Kobe University Hospital
- Kanagawa Cancer Center
- Tohoku University Hospital
- Tenri Hospital
- Kindai University Hospital
- Saitama Medical University International Medical Center
- National Cancer Center Hospital
- Aomori Prefectural Central Hospital
- National Hospital Organization Kyushu Cancer Center
- Hiroshima Red Cross & Atomic-bomb Survivors Hospital
- National Hospital Organization Kumamoto Medical Center
- Kumamoto University Hospital
- Osaka Red Cross Hospital
- Osaka Metropolitan University Hospital
- Yamagata University Hospital
- Asan Medical Center
- Samsung Medical Center
- Seoul National University Hospital
- Severance Hospital, Yonsei University Health System
- Hospital General de México SS
- Centro de Investigación Clínica Chapultepec S.A. de C.V.
- Hospital Universitario "José Eleuterio González"
- Centro Especializado en Investigación Clínica S.C.
- Centro de Atencion e Investigacion Clinica en Oncologia SCP
- Szpital Morski im. PCK
- Malopolskie Centrum Medyczne
- Wojew. Szpital Specjalistyczny im. M. Kopernika
- Centro Clinico Academico - Braga
- Centro Hospitalar Universitario do Porto
- IPO Porto
- Centro Hospitalar Vila Nova de Gaia/Espinho | Unit 1 - Clinical Research Office
- Sp. Judetean de Urgenta Dr. Constantin Opris Baia Mare
- S.C. Policlinica de Diagnostic Rapid S.A.
- Fundeni Clinical Institute
- Spitalul Clinic Coltea
- Spitalul Clinic Colentina
- Spitalul Clinic Municipal Filantropia Craiova
- Institutul Regional de Oncologie Iasi
- Spitalul Clinic Judetean de Urgenta Sibiu
- Kemerovo Regional Clinical Hospital
- Clinical Oncological Dispensary of Omsk Region
- Research Institute of Oncology
- RSRI of Hematology and Transfusiology
- Oncology Dispensary #2
- Siberian State Medical University
- Republican Clinical Oncology Dispensary Ufa
- National University Hospital
- National Cancer Center Singapore
- Singapore General Hospital
- Narodny onkologicky ustav
- Outeniqua Cancercare Oncology Unit
- Cancercare Langenhoven
- Albert Alberts Stem Cell Transplant Research Centre
- Constantiaberg Medi Clinic
- Institut Català d'Oncologia Badalona
- Institut Català d'Oncologia Hospitalet
- Hospital Universitario Clinica Puerta de Hierro
- Hospital Regional de Malaga | Oncologia
- Ciutat Sanitaria i Universitaria de la Vall d'Hebron
- Hospital Clínico Universitario Lozano Blesa
- Changhua Christian Hospital
- Chang Gung Memorial Hospital Kaohsiung
- National Cheng Kung University Hospital
- National Taiwan University Hospital
- Taipei Veterans General Hospital
- Pramongkutklao Hospital
- Siriraj Hospital, Mahidol
- Ankara Universitesi Tip Fakultesi Hastanesi
- Trakya Univ. Tip Fak.
- Istanbul Universitesi Istanbul Tip Fakultesi
- Marmara Uni. Tip Fakultesi Pendik Egitim ve Aras. Hastanesi
- Ege Universitesi Tip Fakultesi
- Dokuz Eylul Universitesi Tip Fakultesi
- Erciyes Universitesi Tip Fakultesi
- Ondokuz Mayis Uni Tip Fakultesi
- Karadeniz Teknik Universitesi Tip Fakultesi
- CNE "Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of the Cherkasy Regional Council"
- Communal Non-Profit Enterprise "City Clinical Hospital No. 4" of the Dnipro City Council
- State non-profit enterprise "National Cancer Institute"
- Institute of Blood Pathology and Transfusion medicine
- Zaporizhzhia Regional Clinical Hospital
- Royal Devon & Exeter Hospital
- Northwick Park Hospital
- Dorset County Hospital
- St George's Hospital
- Singleton Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Copanlisib + R-B or R-CHOP / Arm 1
Placebo + R-B or R-CHOP / Arm 2
Arm Description
Combination of copanlisib with standard immunochemotherapy (rituximab and bendamustine) [R-B] or rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone [R-CHOP] (safety run-in and phase III)
Combination of placebo and R-B or R-CHOP (phase III only)
Outcomes
Primary Outcome Measures
Safety run-in_Determination of the recommended Phase-III dose (RP3D) of copanlisib in combination with standard immunochemotherapy assessed by the occurrence of dose-limiting toxicities / adverse events
Phase III_Evaluation whether copanlisib in combination with standard immunochemotherapy is superior to placebo and standard immunochemotherapy assessed by the prolongation of progression free survival (PFS)
Progression free survival is defined as the time (in days) from randomization to disease progression or death from any cause (if no progression documented).
Secondary Outcome Measures
Safety run-in_Best Overall Response (BOR)
Safety run-in_Number of participants with treatment-emergent adverse events
Phase III_Objective tumor response rate (ORR)
Proportion of patients who have a best overall response over the whole duration of the study (i.e. up to time of analysis of PFS) of complete response (CR) or partial response (PR) according to the Lugano Classification and for patients with Waldenström macroglobulinemia a best overall response of CR, very good partial response (VGPR), PR, or minor response (MR) according to the Owen Criteria.
Phase III_Duration of tumor response (DOR)
Time (in days) from first observed tumor response (complete response [CR], very good partial response [VGPR], partial response [PR], or minor response [MR]) until PD or death from any cause, whichever is earlier. DOR will only be analyzed for patients with at least one CR, VGPR, PR, or MR.
Phase III_Complete tumor response rate (CRR)
Proportion of patients who have a best overall response of CR during the study (i.e., up to time of analysis of PFS).
Phase III_Time to tumor progression (TTP)
Time from randomization to PD or death related to PD, whichever is earlier.
Phase III_Time to next anti-lymphoma treatment (TTNT)
Time from stop of study medication to start of new anti-lymphoma therapy.
Phase III_Overall survival (OS)
The time (in days) from randomization until death from any cause.
Phase III_Time to improvement in disease-related physical symptoms measured by Lymphoma Symptom Index-18 questionnaire
Time to improvement in disease-related physical symptoms (DRS-P) is defined as time from randomization to first increase in DRS-P score of at least 3 points from baseline before tumor progression. Will be evaluated for patients with a baseline DRS-P score of 30 points or less.
The Lymphoma Symptom Index-18 (FLymSI-18) questionnaire measures disease-specific symptoms and/or treatment-related concerns in patients with advanced lymphoma.
Phase III_Time to deterioration in disease-related physical symptoms measured by Lymphoma Symptom Index-18 questionnaire
Time to deterioration in disease-related physical symptoms (DRS-P) is defined as time (in days) from randomization to the earliest occurrence of 1) first reduction of DRS-P score from baseline ≥ 3 points, or 2) radiological progression or biochemical progression for Waldenström macroglobulinemia patients without lesions evaluable by imaging, or 3) death from any cause.
The Lymphoma Symptom Index-18 (FLymSI-18) questionnaire measures disease-specific symptoms and/or treatment-related concerns in patients with advanced lymphoma.
Phase III_Number of participants with treatment-emergent adverse events
Phase III_Disease control rate (DCR)
Proportion of patients who have a best response rating of CR, VGPR, PR, MR, or stable disease (SD) (excluding unconfirmed early SD) that is achieved during treatment or within 35 days after termination of study treatment.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02626455
Brief Title
Study of Copanlisib in Combination With Standard Immunochemotherapy in Relapsed Indolent Non-Hodgkin's Lymphoma (iNHL)
Acronym
CHRONOS-4
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 6, 2016 (Actual)
Primary Completion Date
September 15, 2023 (Actual)
Study Completion Date
April 22, 2030 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
Detailed 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Non-Hodgkin
Keywords
Clinical trial, Phase III, Phosphatidylinositol-3-kinase, Non-Hodgkin's lymphoma, Indolent B-cell non-Hodgkin's lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
551 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Copanlisib + R-B or R-CHOP / Arm 1
Arm Type
Experimental
Arm Description
Combination of copanlisib with standard immunochemotherapy (rituximab and bendamustine) [R-B] or rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone [R-CHOP] (safety run-in and phase III)
Arm Title
Placebo + R-B or R-CHOP / Arm 2
Arm Type
Placebo Comparator
Arm Description
Combination of placebo and R-B or R-CHOP (phase III only)
Intervention Type
Drug
Intervention Name(s)
Copanlisib (BAY80-6946)
Intervention Description
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. For patients on R-B dosing of copanlisib will be administered on Days 1, 8 and 15 of each 28-day cycle. Copanlisib will be administered and then rituximab followed by bendamustine. For patients on R-CHOP dosing of copanlisib will be administered on Days 1 and 8 of each 21-day cycle. Treatment with copanlisib/placebo will be continued up to 12 months.
Copanlisib will be administered before rituximab followed by cyclophosphamide, doxorubicin and vincristine infusions. Prednisone/prednisolone tablets to be taken for 5 days.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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 as per copanlisib described above. Applies to the phase III part of the study only.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Intervention Description
Rituximab is administered as an infusion at a dose of 375 mg/m2 body surface on Day 1 of each 28-day cycle for patients assigned to R-B and on Day 2 of each 21-day cycle for patients assigned to R-CHOP.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Intervention Description
Cyclophosphamide is administered as an infusion at a dose of 750 mg/m2 body surface on Day 2 of each 21-day cycle for patients assigned to R-CHOP
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Intervention Description
Doxorubicin is administered as an infusion at a dose of 50 mg/m2 body surface on Day 2 of each 21-day cycle for patients assigned to R-CHOP
Intervention Type
Drug
Intervention Name(s)
Vincristine
Intervention Description
Vincristine is administered as an infusion at a dose of 1.4 mg/m2 body surface (maximum dose 2.0 mg) on Day 2 of each 21-day cycle for patients assigned to R-CHOP
Intervention Type
Drug
Intervention Name(s)
Bendamustine
Intervention Description
Bendamustine is administered as an infusion at a dose of 90 mg/m2 body surface on Day 1 and Day 2 for patients assigned to R-B
Intervention Type
Drug
Intervention Name(s)
Prednisone
Intervention Description
Prednisone is given as 100 mg tablets daily from Day 2 to Day 6 for patients assigned to R-CHOP
Primary Outcome Measure Information:
Title
Safety run-in_Determination of the recommended Phase-III dose (RP3D) of copanlisib in combination with standard immunochemotherapy assessed by the occurrence of dose-limiting toxicities / adverse events
Time Frame
At Cycle 1: 21 days or 28 days
Title
Phase III_Evaluation whether copanlisib in combination with standard immunochemotherapy is superior to placebo and standard immunochemotherapy assessed by the prolongation of progression free survival (PFS)
Description
Progression free survival is defined as the time (in days) from randomization to disease progression or death from any cause (if no progression documented).
Time Frame
Up to 52 months
Secondary Outcome Measure Information:
Title
Safety run-in_Best Overall Response (BOR)
Time Frame
After Cycle 1: Up to 12 months
Title
Safety run-in_Number of participants with treatment-emergent adverse events
Time Frame
Up to 13 months
Title
Phase III_Objective tumor response rate (ORR)
Description
Proportion of patients who have a best overall response over the whole duration of the study (i.e. up to time of analysis of PFS) of complete response (CR) or partial response (PR) according to the Lugano Classification and for patients with Waldenström macroglobulinemia a best overall response of CR, very good partial response (VGPR), PR, or minor response (MR) according to the Owen Criteria.
Time Frame
Up to 52 months
Title
Phase III_Duration of tumor response (DOR)
Description
Time (in days) from first observed tumor response (complete response [CR], very good partial response [VGPR], partial response [PR], or minor response [MR]) until PD or death from any cause, whichever is earlier. DOR will only be analyzed for patients with at least one CR, VGPR, PR, or MR.
Time Frame
Up to 52 months
Title
Phase III_Complete tumor response rate (CRR)
Description
Proportion of patients who have a best overall response of CR during the study (i.e., up to time of analysis of PFS).
Time Frame
Up to 52 months
Title
Phase III_Time to tumor progression (TTP)
Description
Time from randomization to PD or death related to PD, whichever is earlier.
Time Frame
Up to 52 months
Title
Phase III_Time to next anti-lymphoma treatment (TTNT)
Description
Time from stop of study medication to start of new anti-lymphoma therapy.
Time Frame
Up to 52 months
Title
Phase III_Overall survival (OS)
Description
The time (in days) from randomization until death from any cause.
Time Frame
Up to 5 years after last patient´s first treatment
Title
Phase III_Time to improvement in disease-related physical symptoms measured by Lymphoma Symptom Index-18 questionnaire
Description
Time to improvement in disease-related physical symptoms (DRS-P) is defined as time from randomization to first increase in DRS-P score of at least 3 points from baseline before tumor progression. Will be evaluated for patients with a baseline DRS-P score of 30 points or less.
The Lymphoma Symptom Index-18 (FLymSI-18) questionnaire measures disease-specific symptoms and/or treatment-related concerns in patients with advanced lymphoma.
Time Frame
Up to 52 months
Title
Phase III_Time to deterioration in disease-related physical symptoms measured by Lymphoma Symptom Index-18 questionnaire
Description
Time to deterioration in disease-related physical symptoms (DRS-P) is defined as time (in days) from randomization to the earliest occurrence of 1) first reduction of DRS-P score from baseline ≥ 3 points, or 2) radiological progression or biochemical progression for Waldenström macroglobulinemia patients without lesions evaluable by imaging, or 3) death from any cause.
The Lymphoma Symptom Index-18 (FLymSI-18) questionnaire measures disease-specific symptoms and/or treatment-related concerns in patients with advanced lymphoma.
Time Frame
Up to 52 months
Title
Phase III_Number of participants with treatment-emergent adverse events
Time Frame
Up to 52 months
Title
Phase III_Disease control rate (DCR)
Description
Proportion of patients who have a best response rating of CR, VGPR, PR, MR, or stable disease (SD) (excluding unconfirmed early SD) that is achieved during treatment or within 35 days after termination of study treatment.
Time Frame
Up to 52 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
Facility Name
Ironwood Physicians P.C. DBA Ironwood Cancer & Res. Ctr.
City
Chandler
State/Province
Arizona
ZIP/Postal Code
85224
Country
United States
Facility Name
Brian J. LeBerthon, MD
City
West Covina
State/Province
California
ZIP/Postal Code
91790
Country
United States
Facility Name
SCL Health Research at St Joseph's Hospital Denver CO
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Lewis Hall Singletary Oncology Center
City
Thomasville
State/Province
Georgia
ZIP/Postal Code
31792
Country
United States
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Memorial Sloan-Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
New York Cancer and Blood Specialists
City
Port Jefferson Station
State/Province
New York
ZIP/Postal Code
11776
Country
United States
Facility Name
Gabrail Cancer Center
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
Oncology Consultants
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Oncology- McAllen
City
McAllen
State/Province
Texas
ZIP/Postal Code
78503
Country
United States
Facility Name
Calvary Mater Hospital Newcastle
City
Waratah
State/Province
New South Wales
ZIP/Postal Code
2298
Country
Australia
Facility Name
Flinders Medical Centre
City
Bedford Park
State/Province
South Australia
ZIP/Postal Code
5042
Country
Australia
Facility Name
Ashford Cancer Centre Research Pty Ltd
City
Kurralta Park
State/Province
South Australia
ZIP/Postal Code
5037
Country
Australia
Facility Name
The Alfred Hospital
City
Prahran
State/Province
Victoria
ZIP/Postal Code
3181
Country
Australia
Facility Name
Fiona Stanley Hospital
City
Murdoch
State/Province
Western Australia
ZIP/Postal Code
6961
Country
Australia
Facility Name
Eastern Health Integrated Renal Service
City
Box Hill
ZIP/Postal Code
3128
Country
Australia
Facility Name
Institut Jules Bordet/Jules Bordet Instituut
City
Bruxelles - Brussel
ZIP/Postal Code
1000
Country
Belgium
Facility Name
UZ Gent
City
Gent
ZIP/Postal Code
9000
Country
Belgium
Facility Name
UZ Leuven Gasthuisberg
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
CHU de Liège
City
Liege
ZIP/Postal Code
4000
Country
Belgium
Facility Name
Centro Integrado de Oncologia de Curitiba
City
Curitiba
State/Province
Parana
ZIP/Postal Code
80810-050
Country
Brazil
Facility Name
Hospital de Clínicas de Porto Alegre
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90035-903
Country
Brazil
Facility Name
Irmandade Santa Casa de Misericordia de Porto Alegre
City
Porto Alegre
State/Province
Rio Grande Do Sul
ZIP/Postal Code
90050 170
Country
Brazil
Facility Name
Centro de Pesquisas Oncológicas
City
Florianópolis
State/Province
Santa Catarina
ZIP/Postal Code
88034-000
Country
Brazil
Facility Name
Faculdade de Ciencias Medicas-Universidade Estadual Campinas
City
Campinas
State/Province
Sao Paulo
ZIP/Postal Code
130839 970
Country
Brazil
Facility Name
Centro Multidisciplinar de Estudos Clínicos EPP - Ltda.
City
Santo Andre
State/Province
Sao Paulo
Country
Brazil
Facility Name
IEP São Lucas
City
São Paulo
State/Province
Sao Paulo
ZIP/Postal Code
01234-030
Country
Brazil
Facility Name
Hospital das Clínicas da Faculdade de Medicina da USP
City
São Paulo
State/Province
Sao Paulo
ZIP/Postal Code
05403-000.
Country
Brazil
Facility Name
Instituto Nacional do Cancer Jose Alencar Gomes da Silva
City
Rio de Janeiro
ZIP/Postal Code
20230 130
Country
Brazil
Facility Name
Hospital Israelita Albert Einstein | Morumbi - Clinical Research Department
City
Sao Paulo
ZIP/Postal Code
05651-901
Country
Brazil
Facility Name
UMHAT Sveti Georgi
City
Plovdiv
ZIP/Postal Code
4002
Country
Bulgaria
Facility Name
University Multiprofile Hosp. for Active Treat. Sveti Ivan
City
Sofia
ZIP/Postal Code
1431
Country
Bulgaria
Facility Name
SHATHD Spec. Hospi. for Active Treatm. of Haematol. Dis. EAD
City
Sofia
ZIP/Postal Code
1756
Country
Bulgaria
Facility Name
Multiprofile Hospital for Active Treatment Hristo Botev AD
City
Vratsa
ZIP/Postal Code
3000
Country
Bulgaria
Facility Name
Hopital Maisonneuve-Rosemont
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H1T 2M4
Country
Canada
Facility Name
Hopital du Sacre-Coeur de Montreal
City
Montreal
State/Province
Quebec
ZIP/Postal Code
QC H4J 1C5
Country
Canada
Facility Name
Hopital de L'Enfant Jesus
City
Quebec City
State/Province
Quebec
ZIP/Postal Code
G1J 1Z4
Country
Canada
Facility Name
Centre Universitaire de Sante de l'Estrie
City
Sherbrooke
State/Province
Quebec
ZIP/Postal Code
J1H 5N4
Country
Canada
Facility Name
Sociedad de Investigaciones Medicas Ltda
City
Temuco
State/Province
Araucanía
ZIP/Postal Code
4810469
Country
Chile
Facility Name
Centro de Investigaciones Clínicas Vina del Mar Ltda.
City
Vina del Mar
State/Province
Valparaíso
ZIP/Postal Code
2540364
Country
Chile
Facility Name
Instituto Nacional del Cáncer
City
Santiago
ZIP/Postal Code
838-0455
Country
Chile
Facility Name
FuJian Medical University Union Hospital
City
Fuzhou
State/Province
Fujian
ZIP/Postal Code
350001
Country
China
Facility Name
Sun Yat-sen University Cancer Center
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510060
Country
China
Facility Name
Guangdong Provincial People's Hospital
City
Guangzhou
State/Province
Guangdong
ZIP/Postal Code
510100
Country
China
Facility Name
Tumor Hospital of Hebei Province
City
Shijiazhuang
State/Province
Hebei
ZIP/Postal Code
050011
Country
China
Facility Name
Henan Cancer Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450008
Country
China
Facility Name
Jiangsu Cancer Hospital
City
Nanjing
State/Province
Jiangsu
ZIP/Postal Code
210009
Country
China
Facility Name
1st Affiliated hospital of Soochow University
City
Suzhou
State/Province
Jiangsu
ZIP/Postal Code
215006
Country
China
Facility Name
Jilin Cancer Hospital
City
Changchun
State/Province
Jilin
ZIP/Postal Code
130000
Country
China
Facility Name
The Affiliated Hospital of Qingdao University
City
Qingdao
State/Province
Shandong
ZIP/Postal Code
266500
Country
China
Facility Name
West China Hospital Sichuan University
City
Chengdu
State/Province
Sichuan
ZIP/Postal Code
610041
Country
China
Facility Name
The 1st Affiliated Hospital of Zhejiang University
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310000
Country
China
Facility Name
Zhejiang Cancer Hospital
City
Hangzhou
State/Province
Zhejiang
ZIP/Postal Code
310022
Country
China
Facility Name
Beijing Friendship Hospital, Capital Medical University
City
Beijing
ZIP/Postal Code
100050
Country
China
Facility Name
Fifth Medical Center, General Hospital of the Chinese People
City
Beijing
ZIP/Postal Code
100071
Country
China
Facility Name
Fudan University Shanghai Cancer Center
City
Shanghai
ZIP/Postal Code
200030
Country
China
Facility Name
Xinhua Hos Affiliated to SH Jiaotong Uni School of Medicine
City
Shanghai
ZIP/Postal Code
200092
Country
China
Facility Name
Tianjin Medical University Cancer Institiute & Hospital
City
Tianjin
ZIP/Postal Code
300060
Country
China
Facility Name
Tianjin Union Medicine Centre (People's Hospital of Tianjin)
City
Tianjin
ZIP/Postal Code
300121
Country
China
Facility Name
Fakultni Nemocnice Hradec Kralove
City
Hradec Kralove
ZIP/Postal Code
50005
Country
Czechia
Facility Name
Fakultni nemocnice Kralovske Vinohrady
City
Praha 10
ZIP/Postal Code
100 34
Country
Czechia
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Facility Name
Odense OUH, Haematologisk afdeling
City
Odense C
ZIP/Postal Code
5000
Country
Denmark
Facility Name
HUS, Meilahden sairaala
City
Helsinki
ZIP/Postal Code
00290
Country
Finland
Facility Name
Oulun yliopistollinen sairaala
City
Oulu
ZIP/Postal Code
90020
Country
Finland
Facility Name
Tampereen yliopistollinen sairaala, keskussairaala
City
Tampere
ZIP/Postal Code
33521
Country
Finland
Facility Name
Turun yliopistollinen keskussairaala
City
Turku
ZIP/Postal Code
20520
Country
Finland
Facility Name
Centre Hospitalier Universitaire - Angers
City
Angers
ZIP/Postal Code
49933
Country
France
Facility Name
Centre Hospitalier de la Durance - Avignon
City
Avignon
ZIP/Postal Code
84000
Country
France
Facility Name
Centre Hospitalier Intercommunal de la Côte Basque-Bayonne
City
Bayonne
ZIP/Postal Code
64100
Country
France
Facility Name
Centre Hospitalier Universite de Grenoble
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Clinique Victor Hugo - Le Mans
City
Le Mans Cedex 2
ZIP/Postal Code
72015
Country
France
Facility Name
Hôpital Dupuytren
City
Limoges Cedex
ZIP/Postal Code
87042
Country
France
Facility Name
Hôpital Saint-Eloi
City
Montpellier Cedex
ZIP/Postal Code
34295
Country
France
Facility Name
Hopital Hotel Dieu - Nantes
City
Nantes Cedex
ZIP/Postal Code
44093
Country
France
Facility Name
Hôpital Saint Louis
City
Paris
ZIP/Postal Code
75010
Country
France
Facility Name
Centre François Magendie - Pessac
City
Pessac
ZIP/Postal Code
33600
Country
France
Facility Name
Hôpital de la Milétrie
City
Poitiers
ZIP/Postal Code
86021
Country
France
Facility Name
Clinique Saint Anne
City
Strasbourg
ZIP/Postal Code
67000
Country
France
Facility Name
Stauferklinikum Schwäbisch-Gmünd
City
Mutlangen
State/Province
Baden-Württemberg
ZIP/Postal Code
73557
Country
Germany
Facility Name
Gemeinschaftspraxis Dr.Heinrich/ Prof.Bangerter
City
Augsburg
State/Province
Bayern
ZIP/Postal Code
86150
Country
Germany
Facility Name
Klinikum der Universität München Grosshadern
City
München
State/Province
Bayern
ZIP/Postal Code
81377
Country
Germany
Facility Name
Medizinische Hochschule Hannover (MHH)
City
Hannover
State/Province
Niedersachsen
ZIP/Postal Code
30625
Country
Germany
Facility Name
Marienhospital Herne Universitätsklinik
City
Herne
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
44625
Country
Germany
Facility Name
Universitätsklinikum Münster (UKM)
City
Münster
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
48149
Country
Germany
Facility Name
Oncologianova GmbH
City
Recklinghausen
State/Province
Nordrhein-Westfalen
ZIP/Postal Code
45659
Country
Germany
Facility Name
Med. Fakultät der Martin-Luther-Universität Halle-Wittenberg
City
Halle
State/Province
Sachsen-Anhalt
ZIP/Postal Code
06120
Country
Germany
Facility Name
EVANGELISMOS General Hospital of Athens
City
Athens
ZIP/Postal Code
106 76
Country
Greece
Facility Name
LAIKO General Hospital of Athens
City
Athens
ZIP/Postal Code
115 26
Country
Greece
Facility Name
University General Hospital of Athens "ATTIKON"
City
Chaidari
ZIP/Postal Code
12462
Country
Greece
Facility Name
Univ. General Hospital of Larissa
City
Larissa
ZIP/Postal Code
41100
Country
Greece
Facility Name
University General Hospital of Patras
City
Patras
ZIP/Postal Code
26500
Country
Greece
Facility Name
Prince of Wales Hospital Hong Kong
City
Shatin
Country
Hong Kong
Facility Name
Semmelweis University
City
Budapest
ZIP/Postal Code
1083
Country
Hungary
Facility Name
Semmelweis University
City
Budapest
ZIP/Postal Code
1088
Country
Hungary
Facility Name
Orszagos Onkologiai Intezet
City
Budapest
ZIP/Postal Code
1122
Country
Hungary
Facility Name
Somogy Varmegyei Kaposi Mor Oktato Korhaz
City
Kaposvar
ZIP/Postal Code
7400
Country
Hungary
Facility Name
SzSzBMK es EOK Josa Andras Oktatokorhaz
City
Nyiregyhaza
ZIP/Postal Code
4400
Country
Hungary
Facility Name
Pecsi Tudomanyegyetem Klinikai Kozpont
City
Pecs
ZIP/Postal Code
7624
Country
Hungary
Facility Name
Komarom-Esztergom Varmegyei Szent Borbala Korhaz
City
Tatabanya
ZIP/Postal Code
2800
Country
Hungary
Facility Name
Cork University Hospital
City
Cork
Country
Ireland
Facility Name
Mater Misericordiae Hospital
City
Dublin
ZIP/Postal Code
D07 R2WY
Country
Ireland
Facility Name
Rambam Health Corporation
City
Haifa
ZIP/Postal Code
3109601
Country
Israel
Facility Name
Hadassah Hebrew University Hospital Ein Kerem
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Facility Name
Chaim Sheba Medical Center
City
Ramat Gan
ZIP/Postal Code
5262000
Country
Israel
Facility Name
Shamir Medical Center (Assaf Harofeh)
City
Zerifin
ZIP/Postal Code
6093000
Country
Israel
Facility Name
IRCCS Ospedale Policlinico San Martino
City
Genova
State/Province
Liguria
ZIP/Postal Code
16132
Country
Italy
Facility Name
Istituto Clinico Humanitas - Humanitas Mirasole S.p.A.
City
Milano
State/Province
Lombardia
ZIP/Postal Code
20089
Country
Italy
Facility Name
Fondazione IRCCS Policlinico San Matteo
City
Pavia
State/Province
Lombardia
ZIP/Postal Code
27100
Country
Italy
Facility Name
A.O.U. Ospedali Riuniti "Umberto I - G.M.Lancisi - G.Salesi"
City
Ancona
State/Province
Marche
ZIP/Postal Code
60126
Country
Italy
Facility Name
Aichi Cancer Center Hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
464-8681
Country
Japan
Facility Name
Nagoya City University Hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
467-8602
Country
Japan
Facility Name
JCHO Kyushu Hospital
City
Kitakyushu
State/Province
Fukuoka
ZIP/Postal Code
806-8501
Country
Japan
Facility Name
Gunma University Hospital
City
Maebashi
State/Province
Gunma
ZIP/Postal Code
371-8511
Country
Japan
Facility Name
Hyogo Cancer Center
City
Akashi
State/Province
Hyogo
ZIP/Postal Code
673-8558
Country
Japan
Facility Name
Kobe University Hospital
City
Kobe
State/Province
Hyogo
ZIP/Postal Code
650-0017
Country
Japan
Facility Name
Kanagawa Cancer Center
City
Yokohama
State/Province
Kanagawa
ZIP/Postal Code
241-8515
Country
Japan
Facility Name
Tohoku University Hospital
City
Sendai
State/Province
Miyagi
ZIP/Postal Code
980-8574
Country
Japan
Facility Name
Tenri Hospital
City
Tenri
State/Province
Nara
ZIP/Postal Code
632-8552
Country
Japan
Facility Name
Kindai University Hospital
City
Osakasayama
State/Province
Osaka
ZIP/Postal Code
589-8511
Country
Japan
Facility Name
Saitama Medical University International Medical Center
City
Hidaka
State/Province
Saitama
ZIP/Postal Code
350-1298
Country
Japan
Facility Name
National Cancer Center Hospital
City
Chuo-ku
State/Province
Tokyo
ZIP/Postal Code
104-0045
Country
Japan
Facility Name
Aomori Prefectural Central Hospital
City
Aomori
ZIP/Postal Code
030-8553
Country
Japan
Facility Name
National Hospital Organization Kyushu Cancer Center
City
Fukuoka
ZIP/Postal Code
811-1395
Country
Japan
Facility Name
Hiroshima Red Cross & Atomic-bomb Survivors Hospital
City
Hiroshima
ZIP/Postal Code
730-8619
Country
Japan
Facility Name
National Hospital Organization Kumamoto Medical Center
City
Kumamoto
ZIP/Postal Code
860-0008
Country
Japan
Facility Name
Kumamoto University Hospital
City
Kumamoto
ZIP/Postal Code
860-8556
Country
Japan
Facility Name
Osaka Red Cross Hospital
City
Osaka
ZIP/Postal Code
543-8555
Country
Japan
Facility Name
Osaka Metropolitan University Hospital
City
Osaka
ZIP/Postal Code
545-8586
Country
Japan
Facility Name
Yamagata University Hospital
City
Yamagata
ZIP/Postal Code
990-9585
Country
Japan
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
110-744
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
3722
Country
Korea, Republic of
Facility Name
Hospital General de México SS
City
Ciudad de México
State/Province
Distrito Federal
ZIP/Postal Code
06729
Country
Mexico
Facility Name
Centro de Investigación Clínica Chapultepec S.A. de C.V.
City
Morelia
State/Province
Michoacán
ZIP/Postal Code
58260
Country
Mexico
Facility Name
Hospital Universitario "José Eleuterio González"
City
Monterrey
State/Province
Nuevo Leon
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Centro Especializado en Investigación Clínica S.C.
City
Boca del Río
State/Province
Veracruz
ZIP/Postal Code
94290
Country
Mexico
Facility Name
Centro de Atencion e Investigacion Clinica en Oncologia SCP
City
Merida
State/Province
Yucatán
ZIP/Postal Code
97134
Country
Mexico
Facility Name
Szpital Morski im. PCK
City
Gdynia
ZIP/Postal Code
81-519
Country
Poland
Facility Name
Malopolskie Centrum Medyczne
City
Krakow
ZIP/Postal Code
30-510
Country
Poland
Facility Name
Wojew. Szpital Specjalistyczny im. M. Kopernika
City
Lodz
ZIP/Postal Code
93-513
Country
Poland
Facility Name
Centro Clinico Academico - Braga
City
Braga
ZIP/Postal Code
4710-243
Country
Portugal
Facility Name
Centro Hospitalar Universitario do Porto
City
Porto
ZIP/Postal Code
4099-001
Country
Portugal
Facility Name
IPO Porto
City
Porto
ZIP/Postal Code
4200-072
Country
Portugal
Facility Name
Centro Hospitalar Vila Nova de Gaia/Espinho | Unit 1 - Clinical Research Office
City
Vila Nova de Gaia
ZIP/Postal Code
4434-502
Country
Portugal
Facility Name
Sp. Judetean de Urgenta Dr. Constantin Opris Baia Mare
City
Baia Mare
ZIP/Postal Code
430031
Country
Romania
Facility Name
S.C. Policlinica de Diagnostic Rapid S.A.
City
Brasov
ZIP/Postal Code
500152
Country
Romania
Facility Name
Fundeni Clinical Institute
City
Bucharest
ZIP/Postal Code
022328
Country
Romania
Facility Name
Spitalul Clinic Coltea
City
Bucharest
ZIP/Postal Code
030171
Country
Romania
Facility Name
Spitalul Clinic Colentina
City
Bucuresti
ZIP/Postal Code
020125
Country
Romania
Facility Name
Spitalul Clinic Municipal Filantropia Craiova
City
Craiova
ZIP/Postal Code
200143
Country
Romania
Facility Name
Institutul Regional de Oncologie Iasi
City
Iasi
ZIP/Postal Code
700111
Country
Romania
Facility Name
Spitalul Clinic Judetean de Urgenta Sibiu
City
Sibiu
ZIP/Postal Code
550245
Country
Romania
Facility Name
Kemerovo Regional Clinical Hospital
City
Kemerovo
ZIP/Postal Code
650066
Country
Russian Federation
Facility Name
Clinical Oncological Dispensary of Omsk Region
City
Omsk
ZIP/Postal Code
644013
Country
Russian Federation
Facility Name
Research Institute of Oncology
City
Rostov-on-Don
ZIP/Postal Code
344037
Country
Russian Federation
Facility Name
RSRI of Hematology and Transfusiology
City
Saint-Petersburg
ZIP/Postal Code
191024
Country
Russian Federation
Facility Name
Oncology Dispensary #2
City
Sochi
ZIP/Postal Code
354057
Country
Russian Federation
Facility Name
Siberian State Medical University
City
Tomsk
ZIP/Postal Code
634050
Country
Russian Federation
Facility Name
Republican Clinical Oncology Dispensary Ufa
City
Ufa
ZIP/Postal Code
450054
Country
Russian Federation
Facility Name
National University Hospital
City
Singapore
ZIP/Postal Code
119228
Country
Singapore
Facility Name
National Cancer Center Singapore
City
Singapore
ZIP/Postal Code
169610
Country
Singapore
Facility Name
Singapore General Hospital
City
Singapore
ZIP/Postal Code
169856
Country
Singapore
Facility Name
Narodny onkologicky ustav
City
Bratislava
ZIP/Postal Code
833 10
Country
Slovakia
Facility Name
Outeniqua Cancercare Oncology Unit
City
George
State/Province
Eastern Cape
ZIP/Postal Code
6530
Country
South Africa
Facility Name
Cancercare Langenhoven
City
Port Elizabeth
State/Province
Eastern Cape
ZIP/Postal Code
6045
Country
South Africa
Facility Name
Albert Alberts Stem Cell Transplant Research Centre
City
Pretoria
State/Province
Gauteng
ZIP/Postal Code
0044
Country
South Africa
Facility Name
Constantiaberg Medi Clinic
City
Cape Town
State/Province
Western Cape
ZIP/Postal Code
7800
Country
South Africa
Facility Name
Institut Català d'Oncologia Badalona
City
Badalona
State/Province
Barcelona
ZIP/Postal Code
08916
Country
Spain
Facility Name
Institut Català d'Oncologia Hospitalet
City
L'Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Facility Name
Hospital Universitario Clinica Puerta de Hierro
City
Majadahonda
State/Province
Madrid
ZIP/Postal Code
28222
Country
Spain
Facility Name
Hospital Regional de Malaga | Oncologia
City
Malaga
State/Province
Málaga
ZIP/Postal Code
29010
Country
Spain
Facility Name
Ciutat Sanitaria i Universitaria de la Vall d'Hebron
City
Barcelona
ZIP/Postal Code
08023
Country
Spain
Facility Name
Hospital Clínico Universitario Lozano Blesa
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Facility Name
Changhua Christian Hospital
City
Changhua
ZIP/Postal Code
50006
Country
Taiwan
Facility Name
Chang Gung Memorial Hospital Kaohsiung
City
Kaohsiung
ZIP/Postal Code
833
Country
Taiwan
Facility Name
National Cheng Kung University Hospital
City
Tainan
ZIP/Postal Code
704
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
Taipei Veterans General Hospital
City
Taipei
ZIP/Postal Code
11217
Country
Taiwan
Facility Name
Pramongkutklao Hospital
City
Bangkok
ZIP/Postal Code
10400
Country
Thailand
Facility Name
Siriraj Hospital, Mahidol
City
Bangkok
ZIP/Postal Code
10700
Country
Thailand
Facility Name
Ankara Universitesi Tip Fakultesi Hastanesi
City
Ankara
ZIP/Postal Code
6100
Country
Turkey
Facility Name
Trakya Univ. Tip Fak.
City
Edirne
ZIP/Postal Code
22030
Country
Turkey
Facility Name
Istanbul Universitesi Istanbul Tip Fakultesi
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Marmara Uni. Tip Fakultesi Pendik Egitim ve Aras. Hastanesi
City
Istanbul
ZIP/Postal Code
34899
Country
Turkey
Facility Name
Ege Universitesi Tip Fakultesi
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Dokuz Eylul Universitesi Tip Fakultesi
City
Izmir
ZIP/Postal Code
35340
Country
Turkey
Facility Name
Erciyes Universitesi Tip Fakultesi
City
Kayseri
ZIP/Postal Code
38039
Country
Turkey
Facility Name
Ondokuz Mayis Uni Tip Fakultesi
City
Samsun
ZIP/Postal Code
55139
Country
Turkey
Facility Name
Karadeniz Teknik Universitesi Tip Fakultesi
City
Trabzon
ZIP/Postal Code
61080
Country
Turkey
Facility Name
CNE "Clinical Center of Oncology, Hematology, Transplantology and Palliative Care of the Cherkasy Regional Council"
City
Cherkasy
ZIP/Postal Code
18009
Country
Ukraine
Facility Name
Communal Non-Profit Enterprise "City Clinical Hospital No. 4" of the Dnipro City Council
City
Dnipro
ZIP/Postal Code
49102
Country
Ukraine
Facility Name
State non-profit enterprise "National Cancer Institute"
City
Kyiv
ZIP/Postal Code
03022
Country
Ukraine
Facility Name
Institute of Blood Pathology and Transfusion medicine
City
Lviv
ZIP/Postal Code
79044
Country
Ukraine
Facility Name
Zaporizhzhia Regional Clinical Hospital
City
Zaporizhzhya
ZIP/Postal Code
69600
Country
Ukraine
Facility Name
Royal Devon & Exeter Hospital
City
Exeter
State/Province
Devon
ZIP/Postal Code
EX2 5AX
Country
United Kingdom
Facility Name
Northwick Park Hospital
City
Harrow
State/Province
London
ZIP/Postal Code
HA1 3UJ
Country
United Kingdom
Facility Name
Dorset County Hospital
City
Dorchester
ZIP/Postal Code
DT1 2JY
Country
United Kingdom
Facility Name
St George's Hospital
City
London
ZIP/Postal Code
SW17 0QT
Country
United Kingdom
Facility Name
Singleton Hospital
City
Swansea
ZIP/Postal Code
SA2 8QA
Country
United Kingdom
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
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.
Citations:
PubMed Identifier
34389273
Citation
Matasar MJ, Dreyling M, Leppa S, Santoro A, Pedersen M, Buvaylo V, Fletcher M, Childs BH, Zinzani PL. Feasibility of Combining the Phosphatidylinositol 3-Kinase Inhibitor Copanlisib With Rituximab-Based Immunochemotherapy in Patients With Relapsed Indolent B-cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2021 Nov;21(11):e886-e894. doi: 10.1016/j.clml.2021.06.021. Epub 2021 Jul 2.
Results Reference
derived
Links:
URL
https://clinicaltrials.bayer.com/
Description
Click here to find information for studies related to Bayer products. To find this study enter the ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.
Learn more about this trial
Study of Copanlisib in Combination With Standard Immunochemotherapy in Relapsed Indolent Non-Hodgkin's Lymphoma (iNHL)
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