Main
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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register. |
Register:
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EUCTR |
Last refreshed on:
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27 November 2023 |
Main ID: |
EUCTR2015-001088-38-DK |
Date of registration:
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03/11/2015 |
Prospective Registration:
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Yes |
Primary sponsor: |
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Public title:
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A study investigating copanlisib in combination with standard treatment versus standard treatment alone in order to see if copanlisib improves the response to standard treatment in patients with relapsed indolent non-Hodgkin's lymphoma.
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Scientific title:
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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) - CHRONOS-4 - Phase III study of copanlisib with standard immunochemotherapy in relapsed iNHL |
Date of first enrolment:
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13/01/2016 |
Target sample size:
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520 |
Recruitment status: |
Not Recruiting |
URL:
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https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001088-38 |
Study type:
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Interventional clinical trial of medicinal product |
Study design:
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Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2
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Phase:
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Human pharmacology (Phase I): no
Therapeutic exploratory (Phase II): no
Therapeutic confirmatory - (Phase III): yes
Therapeutic use (Phase IV): no
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Countries of recruitment
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Australia
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Austria
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Belgium
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Brazil
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Bulgaria
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Canada
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Chile
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China
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Czech Republic
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Czechia
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Denmark
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Finland
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France
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Germany
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Greece
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Hong Kong
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Hungary
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Ireland
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Israel
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Italy
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Japan
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Korea, Republic of
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Mexico
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Poland
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Portugal
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Romania
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Russian Federation
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Singapore
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Slovakia
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South Africa
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Spain
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Sweden
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Switzerland
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Taiwan
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Thailand
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Turkey
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Ukraine
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United Kingdom
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United States
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Contacts
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Name:
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Bayer Clinical Trials Contact
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Address:
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13342
Berlin
Germany |
Telephone:
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+4930300139003 |
Email:
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clinical-trials-contact@bayer.com |
Affiliation:
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Bayer AG |
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Name:
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Bayer Clinical Trials Contact
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Address:
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13342
Berlin
Germany |
Telephone:
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+4930300139003 |
Email:
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clinical-trials-contact@bayer.com |
Affiliation:
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Bayer AG |
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Key inclusion & exclusion criteria
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Inclusion criteria: Main criteria for inclusion: -Histologically confirmed diagnosis of CD20 positive iNHL with histological subtype limited to: o Follicular lymphoma (FL) G1, G2, or G3a o Small lymphocytic lymphoma (SLL) with absolute lymphocyte count <5x109/L at study entry o Lymphoplasmacytic lymphoma/ Waldenström macroglobulinemia (LPL/WM) o 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; 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 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%. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 260 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 260
Exclusion criteria: - Histologically confirmed diagnosis of follicular lymphoma (FL) 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 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 SOC. - Congestive heart failure > New York Heart Association (NYHA) class 2. - Uncontrolled hypertension despite optimal medical management (per investigator’s assessment).
Age minimum:
Age maximum:
Gender:
Female: yes Male: yes
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Health Condition(s) or Problem(s) studied
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Therapeutic area: Diseases [C] - Cancer [C04]
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Patients with relapsed indolent non-Hodgkin's lymphoma MedDRA version: 23.0
Level: PT
Classification code 10029600
Term: Non-Hodgkin's lymphoma recurrent
System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
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Intervention(s)
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Product Name: Copanlisib Product Code: BAY84-1236 Pharmaceutical Form: Lyophilisate for solution for infusion INN or Proposed INN: Copanlisib Current Sponsor code: BAY 84-1236 Other descriptive name: BAY 80-6946 (AS DIHYDROCHLORID BAY 84-1236) Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 60- Pharmaceutical form of the placebo: Lyophilisate for solution for infusion Route of administration of the placebo: Intravenous use
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Primary Outcome(s)
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Main Objective: Safety run-in part: Primary objective is to determine: The recommended phase III dose (RP3D) of copanlisib in combination with standard immunochemotherapy (rituximab and bendamustine [RB] or rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone [R-CHOP]) to be used in the subsequent phase III part of the study
Phase III part (randomized, controlled trial) Primary objective is: To evaluate whether copanlisib in combination with standard immunochemotherapy, is superior to standard immunochemotherapy in prolonging progression-free survival (PFS), in patients with relapsed indolent non-Hodgkin’s lymphoma, who have received at least one, but at most three lines of treatment, including rituximab, and/or rituximab biosimilars, and/or anti-CD20 monoclonal antibody-based immunochemotherapy and alkylating agents, and for whom the combination of rituximab with either bendamustine or CHOP represents a valid therapeutic option
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Primary end point(s): The primary completion event for this study is PFS (progression assessed by central review or death from any cause if death occurs before progression). The analysis will be performed when approximately 280 PFS events in the FAS are observed.
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Secondary Objective: Safety run-in part The secondary objectives are to evaluate (for patients that stay on treatment after Cycle 1): Radiological and clinical indicators of treatment efficacy Safety and tolerability of copanlisib in combination with R-B/R-CHOP
Phase III part (randomized, controlled trial) Secondary objectives are to evaluate: Other radiological and clinical indicators of treatment efficacy (objective response rate (ORR), duration of response (DOR), complete response rate (CRR), time to progression (TTP), time to next antilymphoma treatment (TTNT), disease control rate (DCR), overall survival (OS, 5 year survival rate), time to improvement and the time to deterioration in diseaserelated symptoms - physical) Safety and tolerability of copanlisib in combination with R-B/R-CHOP
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Timepoint(s) of evaluation of this end point: The analysis will be performed when approximately 280 PFS events in the FAS are observed.
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Secondary Outcome(s)
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Secondary end point(s): Secondary efficacy variables are objective response rate (ORR), duration of response (DOR), complete response rate (CRR), time to progression (TTP), time to next anti-lymphoma treatment (TTNT), disease control rate (DCR), overall survival (OS, 5 year survival rate), time to improvement and the time to deterioration in disease-related symptoms - physical (DRS-P) of at least 3 points of lymphoma as measured by the FLymSI-18 questionnaire (FLymSI = NCCN-FACT Lymphoma Symptom Index).
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Timepoint(s) of evaluation of this end point: All secondary efficacy endpoints will be analyzed in the FAS at the time of the analysis of the primary efficacy endpoint. Depending on study success in the primary efficacy variable in the FAS, the secondary efficacy variables ORR, time to deterioration and time to improvement in DRS-P subscale of FLymSI-18 of at least 3 points will be tested hierarchically in the FAS. ORR will be tested first and, if successful, will be followed by time to deterioration in DRS-P, and finally, if all previous tests are successful, will be followed by time to improvement of DRS-P and OS.
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Secondary ID(s)
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BAY80-6946
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BAY80-6946/17833
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2015-001088-38-FI
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Source(s) of Monetary Support
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Bayer AG
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Ethics review
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Status: Approved
Approval date: 13/01/2016
Contact:
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Results
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Results available:
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Date Posted:
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Date Completed:
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URL:
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