Phase II Copanlisib in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

December 10, 2018 updated by: Bayer

An Open-label, Single-arm Phase II Study in Patients With Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL) to Evaluate Efficacy and Safety of Treatment With Single Agent Copanlisib and the Impact of Biomarkers Thereupon.

To assess the potential efficacy (in terms of objective response) of single agent copanlisib in patients with relapsed or refractory Diffuse large B-cell lymphoma (DLBCL) and assess the relationship between efficacy and a potentially predictive biomarker

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
67

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Box Hill, Australia, 3128
    • New South Wales
      • Kingswood, New South Wales, Australia, 2747
    • Victoria
      • Ballarat, Victoria, Australia, 3350
      • Prahran, Victoria, Australia, 3181
  • Belgium
      • Bruxelles - Brussel, Belgium, 1200
      • Edegem, Belgium, 2650
      • Gent, Belgium, 9000
      • Leuven, Belgium, 3000
    • Antwerpen
      • Wilrijk, Antwerpen, Belgium, 2610
  • Canada
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada, A1B 3V6
    • Ontario
      • Brampton, Ontario, Canada, L6R 3J7
    • Quebec
      • Montreal, Quebec, Canada, H1T 2M4
      • Montreal, Quebec, Canada, H3T 1E2
      • Sherbrooke, Quebec, Canada, J1H 5N4
  • Denmark
      • Aarhus C, Denmark, 8000
      • Odense C, Denmark, 5000
  • France
      • Caen Cedex, France, 14033
      • Creteil, France, 94010
      • Lille, France, 59037
      • PARIS cedex, France, 75475
      • POITIERS cedex, France, 86021
      • Pierre Benite, France, 69310
  • Germany
      • Berlin, Germany, 10967
    • Nordrhein-Westfalen
      • Münster, Nordrhein-Westfalen, Germany, 48149
    • Sachsen
      • Leipzig, Sachsen, Germany
  • Italy
    • Lombardia
      • Milano, Lombardia, Italy, 20089
  • Korea, Republic of
      • Seoul, Korea, Republic of, 110-744
      • Seoul, Korea, Republic of, 05505
  • Singapore
      • Singapore, Singapore, 169610
  • United Kingdom
      • London, United Kingdom, NW1 2PG
    • Cornwall
      • Truro, Cornwall, United Kingdom, TR1 3LJ
    • Hampshire
      • Southampton, Hampshire, United Kingdom, SO16 6YD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Diagnosis of Diffuse large B-cell lymphoma (DLBCL) (de novo or DLBCL transformed from follicular lymphoma on the basis of a tissue biopsy).
  • Received at least one prior therapy for aggressive Non-Hodgkin's Lymphoma (NHL) (DLBCL).
  • Received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) + rituximab or equivalent regimen.
  • Patients must have measurable disease.
  • Not eligible or not willing to receive the high-dose (myeloablative) chemotherapy (HDC) and stem cell transplant (SCT).
  • A fresh tumor biopsy collected during screening and /or archival tumor tissue collected after the last relapse/disease progression.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
  • Left ventricular ejection fraction (LVEF) ≥ the lower limit of normal (LLN) for the Institution. (as per local standard of care) as measured by echocardiogram (ECHO) or Multiple gated acquisition (MUGA) scan.
  • Adequate bone marrow, liver and renal function.

Exclusion Criteria:

  • Any of the following as the only site(s) of disease: palpable lymph nodes not visible on imaging studies, skin lesions, or bone marrow involvement only.
  • Active CTCAE (Common Terminology Criteria for Adverse Events) Grade 3/4 infection.
  • Current central nervous system (CNS) involvement by lymphoma.
  • Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction within the past 6 months before start of study treatment.
  • Uncontrolled arterial hypertension despite optimal medical management (per investigator's opinion).
  • Type I or II diabetes mellitus with HbA1c > 8.5% at Screening.
  • New York Heart Association (NYHA) class III or IV heart disease.
  • History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator).
  • Patients who previously received therapy with copanlisib or other PI3K inhibitors are not eligible for enrollment.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Copanlisib (Aliqopa, BAY80-6946)
Copanlisib (Aliqopa, BAY80-6946) solution for IV infusion (test drug/investigational medicinal product)
Drug: Copanlisib (Aliqopa, BAY80-6946)
Participants assigned to receive copanlisib intravenous (IV) infusion at a dose of 60 mg as single agent on Days 1, 8, and 15 of 28-day treatment cycle. Copanlisib treatment was to be continued until disease progression (PD), unacceptable toxicity, or until another criterion was met for withdrawal from the study treatment

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate (ORR) in Total Population Based on Investigator Assessment
Time Frame: From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The primary efficacy overall response assessment was based on investigator assessment of response.
From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
ORR by CD79b Status Based on Investigator Assessment
Time Frame: From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The primary efficacy overall response assessment was based on investigator assessment of response.
From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
ORR by DLBCL/COO Subtype Based on Investigator Assessment
Time Frame: From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The primary efficacy overall response assessment was based on investigator assessment of response.
From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Duration of Response (DOR) in Total Population
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The duration of response (DOR) was defined as the time from the date of first observed overall response (CR or PR) until radiological PD or death due to any cause, whichever was earlier. DOR was defined for responders only (i.e. participants with a best response of CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
DOR by CD79b Status
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The duration of response (DOR) was defined as the time from the date of first observed overall response (CR or PR) until radiological PD or death due to any cause, whichever was earlier. DOR was defined for responders only (i.e. participants with a best response of CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
DOR by DLBCL/COO Subtype
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The duration of response (DOR) was defined as the time from the date of first observed overall response (CR or PR) until radiological PD or death due to any cause, whichever was earlier. DOR was defined for responders only (i.e. participants with a best response of CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Progression-free Survival (PFS) in Total Population
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The progression-free survival (PFS) was defined as the time from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier, based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
PFS by CD79b Status
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The progression-free survival (PFS) was defined as the time from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier, based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
PFS by DLBCL/COO Subtype
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The progression-free survival (PFS) was defined as the time from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier, based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Overall Survival (OS) in Total Population
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
OS by CD79b Status
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
OS by DLBCL/COO Subtype
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Duration of Stable Disease (DOSD) in Total Population
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The duration of stable disease (DOSD) was defined as the time (in days) from date of start of study treatment to radiological PD or death due to any cause, whichever was earlier. The DOSD was only evaluated in participants failing to achieve a best response of CR or PR, but who achieved SD (stable disease), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Disease Control Rate (DCR) in Total Population
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The disease control rate (DCR) was defined as the percentage of participants who had a best response rating of CR, PR, or SD that was achieved during treatment or within 30 days after termination of study drug. The tumor response was based on investigator assessment according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
DCR by CD79b Status
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The disease control rate (DCR) was defined as the percentage of participants who had a best response rating of CR, PR, or SD that was achieved during treatment or within 30 days after termination of study drug. The tumor response was based on investigator assessment according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
DCR by DLBCL/COO Subtype
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The disease control rate (DCR) was defined as the percentage of participants who had a best response rating of CR, PR, or SD that was achieved during treatment or within 30 days after termination of study drug. The tumor response was based on investigator assessment according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Time Frame: From start of test drug to 30 days after the last test drug intake, assessed up to 2 years after the last participant's first treatment or the last participant dies (whichever occurs first), with an average of 15 weeks for individual participant
A TEAE was defined as any event arising or worsening after the start of study drug administration until 30 days after the last application.
From start of test drug to 30 days after the last test drug intake, assessed up to 2 years after the last participant's first treatment or the last participant dies (whichever occurs first), with an average of 15 weeks for individual participant

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Time to Response (TTR) in Total Population
Time Frame: From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
The time to response (TTR) was defined as the time (days) from start of study treatment to the date of first observed response (first measured CR or PR). TTR was defined for responders only (i.e. participants with CR or PR), based on the investigator assessment of tumor response according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT.
From start of study treatment assessed up to 2 years after the last participant's first treatment or the last participant dies, whichever occurs first
ORR in Total Population Based on Central Imaging Review
Time Frame: From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The overall response assessment for this outcome measure was based on central imaging review.
From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
ORR by CD79b Status Based on Central Imaging Review
Time Frame: From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The overall response assessment for this outcome measure was based on central imaging review.
From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
ORR by DLBCL/COO Subtype Based on Central Imaging Review
Time Frame: From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)
The objective response rate (ORR) was defined as the percentage of participants who had at least one post-baseline overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano Classification, 2014 and assessed by CT/MRI/PET-CT. The overall response assessment for this outcome measure was based on central imaging review.
From start of study treatment assessed up to 24 weeks after the last participant fully evaluable for the primary endpoint started treatment (about 12 months)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Bayer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 8, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 5, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 19, 2018

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 16, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 11, 2015

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 18, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 4, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 10, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2018

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 17119
  • 2014-004848-36 (EudraCT Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

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