Lymphoma, Non-HodgkinPhase 3CHRONOS-2NCT02369016
Phase III Copanlisib in Rituximab-refractory iNHL
A Phase 3 study testing Copanlisib (BAY 80-6946) in people with Lymphoma, Non-Hodgkin, run by Bayer at 21 sites in 10 countries.
Trial summary
To assess the safety of copanlisib. 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 (BAY 80-6946)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 21 sitesin 10 countries
- Study dates
- 22 Sep 2015to 26 Oct 2022
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 B-cell NHL, with histological subtype limited to the following:
- Follicular lymphoma (FL) grade 1-2-3a.
- Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 10*9/L at the time of diagnosis and at study entry.
- Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM).
- Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal).
- Patients must have received two or more prior lines of treatment. A previous regimen is defined as one of the following: at least two months of single-agent therapy, at least two consecutive cycles of polychemotherapy, autologous transplant, radioimmunotherapy.
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- Prior therapy must include rituximab and alkylating agents.Prior exposure to idelalisib or other PI3K inhibitors is acceptable (except to copanlisib) provided that there is no resistance.
- Patients must be refractory to the last rituximab-based treatment, defined as no response or response lasting < 6 months after completion of treatment. Time interval to assess refractoriness will be calculated between the end date (last day) of the last rituximab-containing regimen and the day of diagnosis confirmation of the subsequent relapse.
- Patients must have at least one bi-dimensionally measurable lesion (which has not been previously irradiated) according to the Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification.
- 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.
- ECOG performance status ≤ 1
- Adequate bone marrow, liver and renal function
Who cannot join
- Histologically confirmed diagnosis of FL grade 3b.
- Chronic lymphocytic leukemia (CLL).
- Transformed disease (assessed by investigator):
- histological confirmation of transformation, or
- clinical and laboratory signs: rapid disease progression, high standardized uptake value (SUV) (> 12) by positron emission tomography (PET) at baseline if PET scans are performed (optional).
- Bulky disease - Lymph nodes or tumor mass (except spleen) >= 7cm LD (longest diameter)
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- Known lymphomatous involvement of the central nervous system.
- Uncontrolled arterial hypertension despite optimal medical management (per investigator's assessment).
- Type I or II diabetes mellitus with HbA1c > 8.5% at Screening.
- Known history of human immunodeficiency virus (HIV) infection.
- Active clinically serious infections > CTCAE Grade 2
- Active Hepatitis B or hepatitis C
- History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator)
- History of having received an allogeneic bone marrow or organ transplant
- Positive cytomegalovirus (CMV) PCR test at baseline
- Pregnant or breast-feeding patients
Trial locations and contacts
21 sites in 10 countries.
21 sites in 10 countries
Russia5 sites
Study site
Kazan', 420029
Study site
Kemerovo, 650066
Study site
Moscow, 123182
Study site
Omsk, 644013
Study site
Penza, 440071
South Korea5 sites
Study site
Jeollabuk-do, 561-712
Study site
Jeollanam-do, 58128
Study site
Seoul, Seoul Teugbyeolsi, 03080
Study site
Seoul, 05505
Study site
Seoul, 3722
Brazil3 sites
Study site
Jaú, São Paulo, 17210-120
Study site
São Paulo, São Paulo, 08270-070
Study site
São Paulo
Italy2 sites
Study site
Bologna, Emilia-Romagna, 40138
Study site
Genoa, Liguria, 16132
About this study
Official title: A Randomized, Double-blind Phase III Study of Copanlisib Versus Placebo in Patients With Rituximab-refractory Indolent Non-Hodgkin's Lymphoma (iNHL) - CHRONOS-2
To assess the safety of copanlisib.
- Conditions
- Lymphoma, Non-Hodgkin
- Being tested
- Copanlisib (BAY 80-6946)
- Keywords
- indolent Non-Hodgkin lymphoma, rituximab-refractory
- 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 (BAY 80-6946)Drug
60 mg of experimental drug in solution administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle
| Study group | Role | What they receive |
|---|---|---|
| Copanlisib (BAY 80-6946) | Experimental | patients with rituximab-refractory iNHL Receives: Drug: Copanlisib (BAY 80-6946) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events (TEAE)s
Adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up)
Measured: up to 7 years
Number of Participants With Treatment-emergent Serious Adverse Events (TESAE)s
Serious adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up)
Measured: up to 7 years
Number of Participants With Abnormal Laboratory Parameters
- Above threshold of 10% and reported as TEAEs - any event (Grade 1-4)
Measured: up to 7 years
Number of Participants With Abnormal Vital Signs
- Reported as TEAEs - worst CTCAE grade total -
Measured: up to 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2015 (estimated)
- Study start22 Sep 2015
- Primary completion26 Oct 2022
- Study completion26 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Lymphoma, Non-HodgkinStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02369016
- Sponsor's protocol ID
- 17322
- Other IDs
- 2014-000925-19, 2014
- Acronym
- CHRONOS-2
- Status last verified
- Nov 2023
- First submitted
- 17 Feb 2015
- Last updated
- 18 Nov 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind Phase III Study of Copanlisib Versus Placebo in Patients With Rituximab-refractory Indolent Non-Hodgkin's Lymphoma (iNHL) - CHRONOS-2
- ClinicalTrials.gov ID
- NCT02369016
- Acronym / sponsor ID
- CHRONOS-2 / 17322
- Conditions
- Lymphoma, Non-Hodgkin
- Keywords
- indolent Non-Hodgkin lymphoma, rituximab-refractory
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 22 Sep 2015 (actual)
- Primary completion
- 26 Oct 2022 (actual)
- Study completion
- 26 Oct 2022 (actual)
- First posted
- 23 Feb 2015 (estimated)
- Results
- Posted 18 Nov 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the safety of copanlisib.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Copanlisib (BAY 80-6946) | Experimental | Drug: Copanlisib (BAY 80-6946)patients with rituximab-refractory iNHL |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype limited to the following:
- Patients must have received two or more prior lines of treatment. A previous regimen is defined as one of the following: at least two months of single-agent therapy, at least two consecutive cycles of polychemotherapy, autologous transplant, radioimmunotherapy.
- Prior therapy must include rituximab and alkylating agents.Prior exposure to idelalisib or other PI3K inhibitors is acceptable (except to copanlisib) provided that there is no resistance.
- Patients must be refractory to the last rituximab-based treatment, defined as no response or response lasting < 6 months after completion of treatment. Time interval to assess refractoriness will be calculated between the end date (last day) of the last rituximab-containing regimen and the day of diagnosis confirmation of the subsequent relapse.
- Patients must have at least one bi-dimensionally measurable lesion (which has not been previously irradiated) according to the Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification.
Key exclusion criteria (16 listed)
- Histologically confirmed diagnosis of FL grade 3b.
- Chronic lymphocytic leukemia (CLL).
- Transformed disease (assessed by investigator):
- Bulky disease - Lymph nodes or tumor mass (except spleen) >= 7cm LD (longest diameter)
- Known lymphomatous involvement of the central nervous system.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Copanlisib (BAY 80-6946)60 mg of experimental drug in solution administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle | Drug | Copanlisib (BAY 80-6946) |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events (TEAE)s
Time frame: up to 7 years
Adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up)
Number of Participants With Treatment-emergent Serious Adverse Events (TESAE)s
Time frame: up to 7 years
Serious adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up)
Number of Participants With Abnormal Laboratory Parameters
Time frame: up to 7 years
- Above threshold of 10% and reported as TEAEs - any event (Grade 1-4)
Number of Participants With Abnormal Vital Signs
Time frame: up to 7 years
- Reported as TEAEs - worst CTCAE grade total -
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bayer Study Director study director
Bayer
21 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Copanlisib (BAY 80-6946) in people with Lymphoma, Non-Hodgkin, run by Bayer at 21 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Nov 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 21 sites in Russia, South Korea, Brazil, Italy, Bulgaria and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Nov 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Treatment-emergent Adverse Events (TEAE)s (time frame: up to 7 years). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Nov 2023.