Back to resultsPhase IIa Study of Copanlisib in Relapsed or Refractory Mantle Cell Lymphoma (MCL)
Primary Purpose
Lymphoma, Mantle-Cell
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Copanlisib (BAY80-6946)
Sponsored by
About this trial
This is an interventional treatment trial for Lymphoma, Mantle-Cell
Eligibility Criteria
Inclusion Criteria:
- Histologically confirmed MCL
Patients who have previously received treatment with ibrutinib (modified by amendment 1), including:
- Completion of at least 1 cycle of treatment with ibrutinib and confirmed evidence of disease progression or refractoriness to treatment or
- Discontinuation of ibrutinib treatment at an earlier time due to toxicity
- Measurable disease according to the Lugano Classification
- At least 28 days or 5 half-lives, whichever is shorter, from the completion of anti-cancer treatment (including, but not limited to, immunotherapy, chemotherapy, targeted therapy and biologic therapy) to the start of study treatment, excluding ibrutinib where the window may be less and at minimum 3 days (modified by amendment 1)
- Availability of fresh tumor tissue at screening
- Male or female patients ≥ 18 years old
- ECOG (Eastern Cooperative Oncology Group) performance status of ≤ 2
- Left ventricular ejection fraction (LVEF) by echocardiogram or multiple gated acquisition (MUGA) scan ≥ the lower limit of normal (LLN) for the Institution
- 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
- Current central nervous system (CNS) involvement by lymphoma
- New York Heart Association (NYHA) class III or IV heart disease
- Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of study treatment
- Uncontrolled arterial hypertension despite optimal medical management (per investigator's assessment) (modified by amendment 1)
- Type I or II diabetes mellitus with HbA1c > 8.5% at screening (modified by amendment 1)
- Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before start of study treatment. However, if a patient has recovered to ECOG performance status of ≤ 2 he/she may be enrolled provided that other eligibility criteria are met
- Ongoing or active infection of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 3
- Known history of human immunodeficiency virus (HIV) infection
- Acute or chronic hepatitis B (HBV) or hepatitis C (HCV) infection requiring concomitant treatment prohibited by this protocol (i.e.immunosuppressive therapy)
- History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator)
- Prior treatment with PI3K inhibitor(s)
- Cytomegalovirus (CMV) PCR positive at baseline
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Copanlisib
Arm Description
Copanlisib (BAY80-6946) solution for IV infusion
Outcomes
Primary Outcome Measures
Objective response rate (ORR)
ORR is defined as the proportion of patients who have a best overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano response criteria in NHL 2014.
Secondary Outcome Measures
Complete response rate (CRR)
Defined as the proportion of patients who have a best overall response of CR during study conduct according to the criteria defined by the Lugano response criteria in NHL 2014
Disease control rate (DCR)
Defined as the proportion of patients who have a best response of CR, PR, or stable disease (SD)
Progression-free survival (PFS)
Defined as the time (in days) from the date of first administration of study treatment to radiological disease progression or death from any cause (if death occurs before radiological progression is documented). PFS for patients without radiological progression or death at the time of analysis will be censored at the last date of evaluable tumor assessment. PFS for alive patients who have no tumor assessments after baseline will be censored at day 1.
Duration of response (DOR)
Defined as the time (in days) from the date of first observed tumor response of CR or PR, whichever was noted earlier, to radiological disease progression or death from any cause (if death occurs before radiological progression is documented)
Overall survival (OS)
Defined as the time (in days) from the date of first administration of study treatment to death from any cause. The OS time for patients alive at the time of analysis will be censored at their last known alive date.
Number of participants with treatment emergent adverse events (TEAEs) as a measure of safety and tolerability
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02455297
Brief Title
Phase IIa Study of Copanlisib in Relapsed or Refractory Mantle Cell Lymphoma (MCL)
Official Title
A Single-arm, Open-label Phase IIa Study to Evaluate the Efficacy and Safety of Copanlisib Monotherapy in Patients With Relapsed or Refractory Mantle Cell Lymphoma (MCL), Who Failed Ibrutinib Treatment or Were Unable to Tolerate Ibrutinib
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Terminated
Study Start Date
August 24, 2015 (Actual)
Primary Completion Date
April 8, 2016 (Actual)
Study Completion Date
August 31, 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of this study is to assess objective response rate (ORR) in patients with relapsed or refractory MCL who failed ibrutinib treatment or were unable to tolerate ibrutinib.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma, Mantle-Cell
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
4 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Copanlisib
Arm Type
Experimental
Arm Description
Copanlisib (BAY80-6946) solution for IV infusion
Intervention Type
Drug
Intervention Name(s)
Copanlisib (BAY80-6946)
Intervention Description
Starting dose 60 mg (dose reduction due to toxicities to 45 mg allowed). Administered in slow IV bolus on days 1, 8 and 15 of each 28 day cycle until disease progression or until another criterion is met for withdrawal from study treatment.
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
ORR is defined as the proportion of patients who have a best overall response of complete response (CR) or partial response (PR) during study conduct according to the criteria defined by the Lugano response criteria in NHL 2014.
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Complete response rate (CRR)
Description
Defined as the proportion of patients who have a best overall response of CR during study conduct according to the criteria defined by the Lugano response criteria in NHL 2014
Time Frame
24 weeks
Title
Disease control rate (DCR)
Description
Defined as the proportion of patients who have a best response of CR, PR, or stable disease (SD)
Time Frame
24 weeks
Title
Progression-free survival (PFS)
Description
Defined as the time (in days) from the date of first administration of study treatment to radiological disease progression or death from any cause (if death occurs before radiological progression is documented). PFS for patients without radiological progression or death at the time of analysis will be censored at the last date of evaluable tumor assessment. PFS for alive patients who have no tumor assessments after baseline will be censored at day 1.
Time Frame
24 weeks
Title
Duration of response (DOR)
Description
Defined as the time (in days) from the date of first observed tumor response of CR or PR, whichever was noted earlier, to radiological disease progression or death from any cause (if death occurs before radiological progression is documented)
Time Frame
24 weeks
Title
Overall survival (OS)
Description
Defined as the time (in days) from the date of first administration of study treatment to death from any cause. The OS time for patients alive at the time of analysis will be censored at their last known alive date.
Time Frame
24 weeks
Title
Number of participants with treatment emergent adverse events (TEAEs) as a measure of safety and tolerability
Time Frame
Approximately 7 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Histologically confirmed MCL
Patients who have previously received treatment with ibrutinib (modified by amendment 1), including:
Completion of at least 1 cycle of treatment with ibrutinib and confirmed evidence of disease progression or refractoriness to treatment or
Discontinuation of ibrutinib treatment at an earlier time due to toxicity
Measurable disease according to the Lugano Classification
At least 28 days or 5 half-lives, whichever is shorter, from the completion of anti-cancer treatment (including, but not limited to, immunotherapy, chemotherapy, targeted therapy and biologic therapy) to the start of study treatment, excluding ibrutinib where the window may be less and at minimum 3 days (modified by amendment 1)
Availability of fresh tumor tissue at screening
Male or female patients ≥ 18 years old
ECOG (Eastern Cooperative Oncology Group) performance status of ≤ 2
Left ventricular ejection fraction (LVEF) by echocardiogram or multiple gated acquisition (MUGA) scan ≥ the lower limit of normal (LLN) for the Institution
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
Current central nervous system (CNS) involvement by lymphoma
New York Heart Association (NYHA) class III or IV heart disease
Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of study treatment
Uncontrolled arterial hypertension despite optimal medical management (per investigator's assessment) (modified by amendment 1)
Type I or II diabetes mellitus with HbA1c > 8.5% at screening (modified by amendment 1)
Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis or pulmonary embolism within 3 months before start of study treatment. However, if a patient has recovered to ECOG performance status of ≤ 2 he/she may be enrolled provided that other eligibility criteria are met
Ongoing or active infection of Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥ 3
Known history of human immunodeficiency virus (HIV) infection
Acute or chronic hepatitis B (HBV) or hepatitis C (HCV) infection requiring concomitant treatment prohibited by this protocol (i.e.immunosuppressive therapy)
History or concurrent condition of interstitial lung disease of any severity and/or severely impaired lung function (as judged by the investigator)
Prior treatment with PI3K inhibitor(s)
Cytomegalovirus (CMV) PCR positive at baseline
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Phase IIa Study of Copanlisib in Relapsed or Refractory Mantle Cell Lymphoma (MCL)
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