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

Phase 2

Completed

• Conditions: Diffuse, Large B-Cell, Lymphoma
• Interventions: Drug: Copanlisib (Aliqopa, BAY80-6946)

• Registration Number: NCT02391116
• Lead Sponsor: 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2015-02-16
• Study First Submitted QC: 2015-03-11
• Study First Posted: 2015-03-18
• Study Start: 2015-05-08
• Primary Completion: 2016-07-05
• Disposition First Submitted: 2016-10-13
• Disposition First Submitted QC: 2016-10-13
• Disposition First Posted: 2016-10-14
• Results First Submitted: 2017-10-13
• Results First Submitted QC: 2017-12-08
• Results First Posted: 2018-01-08
• Study Completion: 2018-01-19
• Status Verified: 2018-12
• Last Update Submitted: 2018-12-10
• Last Update Posted: 2019-01-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 67

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Copanlisib (Aliqopa, BAY80-6946)	Copanlisib (Aliqopa, BAY80-6946)	Copanlisib (Aliqopa, BAY80-6946) solution for IV infusion (test drug/investigational medicinal product)

Primary Outcome Measures

Name	Time	Method
ORR by DLBCL/COO Subtype Based on Investigator Assessment	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.
Objective Response Rate (ORR) in Total Population Based on Investigator Assessment	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	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 Outcome Measures

Name	Time	Method
OS by DLBCL/COO Subtype	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.
DOR by DLBCL/COO Subtype	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.
Disease Control Rate (DCR) in Total Population	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	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	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.
DOR by CD79b Status	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.
PFS by CD79b Status	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.
OS by CD79b Status	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	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.
Duration of Response (DOR) in Total Population	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	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	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	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.
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	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.