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

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ClinicalTrials.gov Identifier: NCT02391116
Recruitment Status : Completed
First Posted : March 18, 2015
Results First Posted : January 8, 2018
Last Update Posted : January 4, 2019
Sponsor:
Information provided by (Responsible Party):
Bayer

Tracking Information
First Submitted Date  ICMJE February 16, 2015
First Posted Date  ICMJE March 18, 2015
Results First Submitted Date  ICMJE October 13, 2017
Results First Posted Date  ICMJE January 8, 2018
Last Update Posted Date January 4, 2019
Actual Study Start Date  ICMJE May 8, 2015
Actual Primary Completion Date July 5, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 10, 2018)
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 11, 2015)
  • Objective Response [ Time Frame: 24 weeks after the last patient fully evaluable for the primary endpoint started treatment. ]
    Number of patients who have at least once a post baseline overall response of CR (complete response) or PR (partial response) during study conduct; according to the criteria defined by Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification
  • Objective response in CD79B mutant patient population [ Time Frame: 24 weeks after the last patient fully evaluable for the primary endpoint started treatment ]
  • Objective response in CD79B wild-type patient population [ Time Frame: 24 weeks after the last patient fully evaluable for the primary endpoint started treatment. ]
  • Objective response in cell-of-origin ABC patient population [ Time Frame: 24 weeks after the last patient fully evaluable for the primary endpoint started treatment ]
  • Objective response in cell-of-origin GCB patient population [ Time Frame: 24 weeks after the last patient fully evaluable for the primary endpoint started treatment ]
  • Objective response in unclassifiable cell-of-origin patient population [ Time Frame: 24 weeks after the last patient fully evaluable for the primary endpoint started treatment ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 11, 2015)
  • Duration of response (DOR) [ Time Frame: Up to 24 weeks after the last patient fully evaluable for the primary endpoint started treatment ]
    DOR is defined as the time from the date of first observed overall response (CR or PR) until first subsequent disease progression (PD) or until death (if death occurs before progression is documented) caused by disease progression. Duration of response will be defined for responders only (i.e., patients with CR or PR).
  • Progression-free survival (PFS) [ Time Frame: Up to 24 weeks after the last patient fully evaluable for the primary endpoint started treatment ]
    PFS is defined as the time from enrollment (i.e., date of treatment assignment) to disease progression (radiological or clinical, whichever is earlier) or death (if death occurs before progression is documented)
  • Overall survival (OS) [ Time Frame: Up to 24 weeks after the last patient fully evaluable for the primary endpoint started treatment ]
    OS is defined as the time from enrollment (i.e., date of treatment assignment) until death from any cause or until the last date the patient is known to be alive
  • Disease control rate (DCR) [ Time Frame: Up to 24 weeks after the last patient fully evaluable for the primary endpoint started treatment. ]
    DCR is defined as the proportion of patients who have a best response rating of CR, PR, or SD that is achieved during treatment or within 30 days after termination of study treatment
  • Duration of stable disease (DOSD) [ Time Frame: Up to 24 weeks after the last patient fully evaluable for the primary endpoint started treatment ]
    DOSD will only be evaluated in patients failing to achieve a best response of CR or PR, but who achieve SD. DOSD is defined as the time (in days) from date of start of study treatment to the date at which disease progression or death (if death occurs before progression) is first documented
  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: Up to 24 weeks after the last patient fully evaluable for the primary endpoint started treatment ]
Current Other Pre-specified Outcome Measures
 (submitted: December 10, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase II Copanlisib in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)
Official Title  ICMJE 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.
Brief Summary 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
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Diffuse, Large B-Cell, Lymphoma
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: Copanlisib (Aliqopa, BAY80-6946)
Copanlisib (Aliqopa, BAY80-6946) solution for IV infusion (test drug/investigational medicinal product)
Intervention: Drug: Copanlisib (Aliqopa, BAY80-6946)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 17, 2016)
67
Original Estimated Enrollment  ICMJE
 (submitted: March 11, 2015)
66
Actual Study Completion Date  ICMJE January 19, 2018
Actual Primary Completion Date July 5, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Belgium,   Canada,   Denmark,   France,   Germany,   Italy,   Korea, Republic of,   Singapore,   United Kingdom
Removed Location Countries Spain,   Turkey
 
Administrative Information
NCT Number  ICMJE NCT02391116
Other Study ID Numbers  ICMJE 17119
2014-004848-36 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Bayer
Study Sponsor  ICMJE Bayer
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Bayer Study Director Bayer
PRS Account Bayer
Verification Date December 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP