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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 : March 9, 2018
Sponsor:
Information provided by (Responsible Party):
Bayer

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

Condition or disease Intervention/treatment Phase
Diffuse, Large B-Cell, Lymphoma Drug: Copanlisib (BAY80-6946) Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 67 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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.
Actual Study Start Date : May 8, 2015
Actual Primary Completion Date : July 5, 2016
Actual Study Completion Date : January 19, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Copanlisib

Arm Intervention/treatment
Experimental: Copanlisib (BAY80-6946)
Copanlisib (BAY80-6946) solution for IV infusion (test drug/investigational medicinal product)
Drug: Copanlisib (BAY80-6946)
Patients 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.




Primary Outcome Measures :
  1. 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 patient fully evaluable for the primary endpoint started treatment (about 12 months) ]
    The objective response rate (ORR) was defined as the proportion of patients 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.

  2. ORR in Total Population Based on Investigator Assessment [ Time Frame: From start of study treatment assessed up to 24 weeks after the last patient fully evaluable for the primary endpoint started treatment (about 12 months) ]
    The objective response rate (ORR) was defined as the proportion of patients 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.

  3. ORR by CD79b Status Based on Investigator Assessment [ Time Frame: From start of study treatment assessed up to 24 weeks after the last patient fully evaluable for the primary endpoint started treatment (about 12 months) ]
    The objective response rate (ORR) was defined as the proportion of patients 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.

  4. ORR by DLBCL/COO Subtype Based on Investigator Assessment [ Time Frame: From start of study treatment assessed up to 24 weeks after the last patient fully evaluable for the primary endpoint started treatment (about 12 months) ]
    The objective response rate (ORR) was defined as the proportion of patients 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.


Secondary Outcome Measures :
  1. Duration of Response (DOR) in Total Population [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient 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. patients 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.

  2. DOR by CD79b Status [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient 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. patients 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.

  3. DOR by DLBCL/COO Subtype [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient 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. patients 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.

  4. Progression-free Survival (PFS) in Total Population [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient 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.

  5. PFS by CD79b Status [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient 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.

  6. PFS by DLBCL/COO Subtype [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient 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.

  7. Overall Survival (OS) in Total Population [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient 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.

  8. OS by CD79b Status [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient 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.

  9. OS by DLBCL/COO Subtype [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient 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.

  10. Duration of Stable Disease (DOSD) in Total Population [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient 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 patients 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.

  11. Disease Control Rate (DCR) in Total Population [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient dies, whichever occurs first ]
    The disease control rate (DCR) was defined as the proportion of patients 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.

  12. DCR by CD79b Status [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient dies, whichever occurs first ]
    The disease control rate (DCR) was defined as the proportion of patients 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.

  13. DCR by DLBCL/COO Subtype [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient dies, whichever occurs first ]
    The disease control rate (DCR) was defined as the proportion of patients 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.

  14. Number of Patients With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) [ Time Frame: From start of study treatment to 30 days after termination of study drug, assessed up to 2 years after the last patient's first treatment or the last patient dies (whichever occurs first ), with an average of 15 weeks for individual patient ]
    A TEAE was defined as any event arising or worsening after the start of study drug administration until 30 days after the last application.


Other Outcome Measures:
  1. Time to Response (TTR) in Total Population [ Time Frame: From start of study treatment assessed up to 2 years after the last patient's first treatment or the last patient 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. patients 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.

  2. ORR in Total Population Based on Central Imaging Review [ Time Frame: From start of study treatment assessed up to 24 weeks after the last patient fully evaluable for the primary endpoint started treatment (about 12 months) ]
    The objective response rate (ORR) was defined as the proportion of patients 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.

  3. ORR by CD79b Status Based on Central Imaging Review [ Time Frame: From start of study treatment assessed up to 24 weeks after the last patient fully evaluable for the primary endpoint started treatment (about 12 months) ]
    The objective response rate (ORR) was defined as the proportion of patients 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.

  4. 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 patient fully evaluable for the primary endpoint started treatment (about 12 months) ]
    The objective response rate (ORR) was defined as the proportion of patients 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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 + rituximab or equivalent regimen.
  • Patients must have measurable disease.
  • Not eligible or not willing to receive the high-dose (myeloablative) chemotherapy (HDC) and SCT.
  • A fresh tumor biopsy collected during screening and /or archival tumor tissue collected after the last relapse/disease progression.
  • ECOG (Eastern Cooperative Oncology Group) 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02391116


  Show 32 Study Locations
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer

Additional Information:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT02391116     History of Changes
Other Study ID Numbers: 17119
2014-004848-36 ( EudraCT Number )
First Posted: March 18, 2015    Key Record Dates
Results First Posted: January 8, 2018
Last Update Posted: March 9, 2018
Last Verified: February 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin