Clinical trial NCT02391116: Phase II Copanlisib in Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)
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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diffuse, Large B-Cell, Lymphoma
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2015-03-18
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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 (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.

Primary outcomes:
measure: Objective Response Rate (ORR) in Total Population Based on Investigator Assessment
timeFrame: 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)
measure: ORR by CD79b Status Based on Investigator Assessment
timeFrame: 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)
measure: ORR by DLBCL/COO Subtype Based on Investigator Assessment
timeFrame: 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 outcomes:
measure: Duration of Response (DOR) in Total Population
timeFrame: 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
measure: DOR by CD79b Status
timeFrame: 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
measure: DOR by DLBCL/COO Subtype
timeFrame: 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
measure: Progression-free Survival (PFS) in Total Population
timeFrame: 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
measure: PFS by CD79b Status
timeFrame: 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
measure: PFS by DLBCL/COO Subtype
timeFrame: 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
measure: Overall Survival (OS) in Total Population
timeFrame: 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
measure: OS by CD79b Status
timeFrame: 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
measure: OS by DLBCL/COO Subtype
timeFrame: 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
measure: Duration of Stable Disease (DOSD) in Total Population
timeFrame: 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
measure: Disease Control Rate (DCR) in Total Population
timeFrame: 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
measure: DCR by CD79b Status
timeFrame: 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
measure: DCR by DLBCL/COO Subtype
timeFrame: 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
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: 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
Other outcomes:
measure: Time to Response (TTR) in Total Population
timeFrame: 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
measure: ORR in Total Population Based on Central Imaging Review
timeFrame: 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)
measure: ORR by CD79b Status Based on Central Imaging Review
timeFrame: 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)
measure: ORR by DLBCL/COO Subtype Based on Central Imaging Review
timeFrame: 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)
Locations:
city: Kingswood
country: Australia
state: New South Wales
city: Ballarat
country: Australia
state: Victoria
city: Prahran
country: Australia
state: Victoria
city: Box Hill
country: Australia
city: Wilrijk
country: Belgium
state: Antwerpen
city: Bruxelles - Brussel
country: Belgium
city: Edegem
country: Belgium
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: St. John's
country: Canada
state: Newfoundland and Labrador
city: Brampton
country: Canada
state: Ontario
city: Montreal
country: Canada
state: Quebec
city: Montreal
country: Canada
state: Quebec
city: Sherbrooke
country: Canada
state: Quebec
city: Aarhus C
country: Denmark
city: Odense C
country: Denmark
city: Caen Cedex
country: France
city: Creteil
country: France
city: Lille
country: France
city: PARIS cedex
country: France
city: Pierre Benite
country: France
city: POITIERS cedex
country: France
city: Münster
country: Germany
state: Nordrhein-Westfalen
city: Leipzig
country: Germany
state: Sachsen
city: Berlin
country: Germany
city: Milano
country: Italy
state: Lombardia
city: Seoul
country: Korea, Republic of
city: Seoul
country: Korea, Republic of
city: Singapore
country: Singapore
city: Truro
country: United Kingdom
state: Cornwall
city: Southampton
country: United Kingdom
state: Hampshire
city: London
country: United Kingdom
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Lenz G, Hawkes E, Verhoef G, Haioun C, Thye Lim S, Seog Heo D, Ardeshna K, Chong G, Haaber J, Shi W, Gorbatchevsky I, Lippert S, Hiemeyer F, Piraino P, Beckmann G, Pena C, Buvaylo V, Childs BH, Salles G. Single-agent activity of phosphatidylinositol 3-kinase inhibition with copanlisib in patients with molecularly defined relapsed or refractory diffuse large B-cell lymphoma. Leukemia. 2020 Aug;34(8):2184-2197. doi: 10.1038/s41375-020-0743-y. Epub 2020 Feb 14.