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Completed

NCT Number: NCT02391116

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

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

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Key information

Conditions

Diffuse, Large B-Cell, Lymphoma Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Lymphatic Diseases Lymphoma Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Non-Hodgkin Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Kingswood, New South Wales, Australia

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Copanlisib (ALIQOPA, BAY80-6946)

Drug

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

Primary outcomes

  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 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.

  2. 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.

  3. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

Other outcomes

  1. 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.

  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 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.

  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 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.

  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 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.

Sponsors and collaborators

Lead sponsor

Bayer

Industry

Registry information

Official study 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.

Important dates

Study start
2015
Primary completion
2016
Study completion
2018
First posted
Mar 18, 2015
Registry last updated
Jan 4, 2019

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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