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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02391116




Registration number
NCT02391116
Ethics application status
Date submitted
16/02/2015
Date registered
18/03/2015
Date last updated
4/01/2019

Titles & IDs
Public title
Phase II Copanlisib in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)
Scientific title
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.
Secondary ID [1] 0 0
2014-004848-36
Secondary ID [2] 0 0
17119
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Diffuse, Large B-Cell, Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Copanlisib (Aliqopa, BAY80-6946)

Experimental: Copanlisib (Aliqopa, BAY80-6946) - Copanlisib (Aliqopa, BAY80-6946) solution for IV infusion (test drug/investigational medicinal product)


Treatment: Drugs: 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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Objective Response Rate (ORR) in Total Population Based on Investigator Assessment
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
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)
Primary outcome [2] 0 0
ORR by CD79b Status Based on Investigator Assessment
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
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)
Primary outcome [3] 0 0
ORR by DLBCL/COO Subtype Based on Investigator Assessment
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
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 [1] 0 0
Duration of Response (DOR) in Total Population
Assessment method [1] 0 0
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.
Timepoint [1] 0 0
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
Secondary outcome [2] 0 0
DOR by CD79b Status
Assessment method [2] 0 0
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.
Timepoint [2] 0 0
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
Secondary outcome [3] 0 0
DOR by DLBCL/COO Subtype
Assessment method [3] 0 0
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.
Timepoint [3] 0 0
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
Secondary outcome [4] 0 0
Progression-free Survival (PFS) in Total Population
Assessment method [4] 0 0
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.
Timepoint [4] 0 0
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
Secondary outcome [5] 0 0
PFS by CD79b Status
Assessment method [5] 0 0
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.
Timepoint [5] 0 0
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
Secondary outcome [6] 0 0
PFS by DLBCL/COO Subtype
Assessment method [6] 0 0
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.
Timepoint [6] 0 0
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
Secondary outcome [7] 0 0
Overall Survival (OS) in Total Population
Assessment method [7] 0 0
The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.
Timepoint [7] 0 0
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
Secondary outcome [8] 0 0
OS by CD79b Status
Assessment method [8] 0 0
The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
OS by DLBCL/COO Subtype
Assessment method [9] 0 0
The overall survival (OS) was defined as the time from date of start of study treatment until death from any cause.
Timepoint [9] 0 0
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
Secondary outcome [10] 0 0
Duration of Stable Disease (DOSD) in Total Population
Assessment method [10] 0 0
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.
Timepoint [10] 0 0
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
Secondary outcome [11] 0 0
Disease Control Rate (DCR) in Total Population
Assessment method [11] 0 0
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.
Timepoint [11] 0 0
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
Secondary outcome [12] 0 0
DCR by CD79b Status
Assessment method [12] 0 0
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.
Timepoint [12] 0 0
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
Secondary outcome [13] 0 0
DCR by DLBCL/COO Subtype
Assessment method [13] 0 0
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.
Timepoint [13] 0 0
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
Secondary outcome [14] 0 0
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Assessment method [14] 0 0
A TEAE was defined as any event arising or worsening after the start of study drug administration until 30 days after the last application.
Timepoint [14] 0 0
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

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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 design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/05/2015
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/01/2018
Sample size
Target
Accrual to date
Final
67
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
- Kingswood
Recruitment hospital [2] 0 0
- Ballarat
Recruitment hospital [3] 0 0
- Prahran
Recruitment hospital [4] 0 0
- Box Hill
Recruitment postcode(s) [1] 0 0
2747 - Kingswood
Recruitment postcode(s) [2] 0 0
3350 - Ballarat
Recruitment postcode(s) [3] 0 0
3181 - Prahran
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment outside Australia
Country [1] 0 0
Belgium
State/province [1] 0 0
Antwerpen
Country [2] 0 0
Belgium
State/province [2] 0 0
Bruxelles - Brussel
Country [3] 0 0
Belgium
State/province [3] 0 0
Edegem
Country [4] 0 0
Belgium
State/province [4] 0 0
Gent
Country [5] 0 0
Belgium
State/province [5] 0 0
Leuven
Country [6] 0 0
Canada
State/province [6] 0 0
Newfoundland and Labrador
Country [7] 0 0
Canada
State/province [7] 0 0
Ontario
Country [8] 0 0
Canada
State/province [8] 0 0
Quebec
Country [9] 0 0
Denmark
State/province [9] 0 0
Aarhus C
Country [10] 0 0
Denmark
State/province [10] 0 0
Odense C
Country [11] 0 0
France
State/province [11] 0 0
Caen Cedex
Country [12] 0 0
France
State/province [12] 0 0
Creteil
Country [13] 0 0
France
State/province [13] 0 0
Lille
Country [14] 0 0
France
State/province [14] 0 0
PARIS cedex
Country [15] 0 0
France
State/province [15] 0 0
Pierre Benite
Country [16] 0 0
France
State/province [16] 0 0
POITIERS cedex
Country [17] 0 0
Germany
State/province [17] 0 0
Nordrhein-Westfalen
Country [18] 0 0
Germany
State/province [18] 0 0
Sachsen
Country [19] 0 0
Germany
State/province [19] 0 0
Berlin
Country [20] 0 0
Italy
State/province [20] 0 0
Lombardia
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul
Country [22] 0 0
Singapore
State/province [22] 0 0
Singapore
Country [23] 0 0
United Kingdom
State/province [23] 0 0
Cornwall
Country [24] 0 0
United Kingdom
State/province [24] 0 0
Hampshire
Country [25] 0 0
United Kingdom
State/province [25] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Bayer
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Bayer Study Director
Address 0 0
Bayer
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT02391116