Clinical Trials List
Protocol NumberBAY 80-6946 / 17833
NCT Number(ClinicalTrials.gov Identfier)NCT02626455
2017-07-20 - 2025-05-20
Phase III
Recruiting1
Terminated4
ICD-10C85
Other specified and unspecified types of non-Hodgkin lymphoma
A Phase III, Randomized, Double-blind, Controlled Multicenter Study of Intravenous PI3K Inhibitor Copanlisib in Combination With Standard Immunochemotherapy Versus Standard Immunochemotherapy in Patients With Relapsed Indolent Non-Hodgkin's Lymphoma (iNHL)
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Trial Applicant
BAYER TAIWAN COMPANY LTD.
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Sponsor
Bayer
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Tai-Chung Huang 無
- Shang-Ju Wu 無
- SHAN-CHI YU 無
- 劉高郎 無
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Co-Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
Principal Investigator
The Actual Total Number of Participants Enrolled
0 Terminated
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Sin-Syue Li 無
- Ya-Ting Hsu 無
- Ya-Ping Chen 無
- Wei-Pang Chung 無
- Yu-Min Yeh 無
- 劉奕廷 無
- Shang-Yin Wu 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Lymphoma, Non-Hodgkin
Objectives
The purpose of this study is to assess whether copanlisib in combination with standard immunochemotherapy (rituximab in combination with bendamustine [R-B] and rituximab in combination with a 4 drug combination of cyclophosphamide, doxorubicin, vincristine and prednisone/prednisolone [R-CHOP]) is effective and safe, compared with placebo in combination with standard immunochemotherapy (R-B or R-CHOP) in patients with relapsed iNHL who have received at least one, but at most three, lines of treatment, including rituximab-based immunochemotherapy and alkylating agents.
Test Drug
BAY 80-6946 (copanlisib)；phosphatidylinositol 3-kinase (PI3K) inhibitor
Active Ingredient
Copanlisib
Dosage Form
Injection
Dosage
45 mg, 60 mg
Endpoints
Primary Outcome Measures:
1. Safety run-in_Determination of the recommended Phase-III dose (RP3D) of copanlisib in combination with standard immunochemotherapy assessed by the occurrence of dose-limiting toxicities / adverse events.
2. Phase III_Evaluation whether copanlisib in combination with standard immunochemotherapy is superior to placebo and standard immunochemotherapy assessed by the prolongation of progression free survival (PFS).
Secondary Outcome Measures:
1. Safety run-in_Best Overall Response (BOR).
2. Safety run-in_Number of participants with treatment-emergent adverse events.
3. Phase III_Objective tumor response rate (ORR).
4. Phase III_Duration of tumor response (DOR).
5. Phase III_Complete tumor response rate (CRR).
6. Phase III_Time to tumor progression (TTP).
7. Phase III_Time to next anti-lymphoma treatment (TTNT).
8. Phase III_Overall survival (OS).
9. Phase III_Time to improvement in disease-related physical symptoms measured by Lymphoma Symptom Index-18 questionnaire.
10. Phase III_Time to deterioration in disease-related physical symptoms.
11. Phase III_Number of participants with treatment-emergent adverse events.
1. Safety run-in_Determination of the recommended Phase-III dose (RP3D) of copanlisib in combination with standard immunochemotherapy assessed by the occurrence of dose-limiting toxicities / adverse events.
2. Phase III_Evaluation whether copanlisib in combination with standard immunochemotherapy is superior to placebo and standard immunochemotherapy assessed by the prolongation of progression free survival (PFS).
Secondary Outcome Measures:
1. Safety run-in_Best Overall Response (BOR).
2. Safety run-in_Number of participants with treatment-emergent adverse events.
3. Phase III_Objective tumor response rate (ORR).
4. Phase III_Duration of tumor response (DOR).
5. Phase III_Complete tumor response rate (CRR).
6. Phase III_Time to tumor progression (TTP).
7. Phase III_Time to next anti-lymphoma treatment (TTNT).
8. Phase III_Overall survival (OS).
9. Phase III_Time to improvement in disease-related physical symptoms measured by Lymphoma Symptom Index-18 questionnaire.
10. Phase III_Time to deterioration in disease-related physical symptoms.
11. Phase III_Number of participants with treatment-emergent adverse events.
Inclution Criteria
1. Histologically confirmed diagnosis of B lymphocyte antigen CD20 positive iNHL with histological subtype limited to:
(1) Follicular lymphoma G1-2-3a
(2) Small lymphocytic lymphoma with absolute lymphocyte count <5x10E9/L at study entry
(3) Lymphoplasmacytoid lymphoma / Waldenström macroglobulinemia (LPL / WM)
(4) Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)
2. Patients must have relapsed (recurrence after complete response or presented progression after partial response) or progressed after at least one but at most three prior lines of therapy, including rituximab, and/or rituximab biosimilars, and/or anti-CD20 monoclonal antibody (e.g. obinutuzumab) -based immunochemotherapy and alkylating agents (if given concomitantly is considered one line of therapy). A previous regimen is defined as one of the following: at least 2 months of single-agent therapy (less than 2 months of therapy with single agent rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody can be considered a previous regimen in the case the patient responded to it); at least 2 consecutive cycles of polychemotherapy; autologous transplant; or radioimmunotherapy. Previous exposure to other PI3K Inhibitors (except copanlisib) is acceptable provided there is no resistance (resistance defined as no response (response defined as partial response [PR] or complete response [CR]) at any time during therapy, or progressive disease (PD) after any response (PR/CR) or after stable disease within 6 months from the end of the therapy with a PI3K inhibitor.
3. Non-WM patients must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) according to the Lugano Classification. For patients with splenic MZL this requirement may be restricted to splenomegaly alone since that is usually the only manifestation of measurable disease.
4. Patients affected by WM who do not have at least one bi-dimensionally measurable lesion in the baseline radiologic assessment must have measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level ≥ 2 x upper limit of normal and positive immunofixation test.
5. Male or female patients ≥ 18 years of age
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
7. Life expectancy of at least 3 months
8. Availability of fresh tumor tissue and/or archival tumor tissue at Screening
9. Adequate baseline laboratory values as assessed within 7 days before starting study treatment.
10. Left ventricular ejection fraction ≥ 50%
(1) Follicular lymphoma G1-2-3a
(2) Small lymphocytic lymphoma with absolute lymphocyte count <5x10E9/L at study entry
(3) Lymphoplasmacytoid lymphoma / Waldenström macroglobulinemia (LPL / WM)
(4) Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal)
2. Patients must have relapsed (recurrence after complete response or presented progression after partial response) or progressed after at least one but at most three prior lines of therapy, including rituximab, and/or rituximab biosimilars, and/or anti-CD20 monoclonal antibody (e.g. obinutuzumab) -based immunochemotherapy and alkylating agents (if given concomitantly is considered one line of therapy). A previous regimen is defined as one of the following: at least 2 months of single-agent therapy (less than 2 months of therapy with single agent rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody can be considered a previous regimen in the case the patient responded to it); at least 2 consecutive cycles of polychemotherapy; autologous transplant; or radioimmunotherapy. Previous exposure to other PI3K Inhibitors (except copanlisib) is acceptable provided there is no resistance (resistance defined as no response (response defined as partial response [PR] or complete response [CR]) at any time during therapy, or progressive disease (PD) after any response (PR/CR) or after stable disease within 6 months from the end of the therapy with a PI3K inhibitor.
3. Non-WM patients must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) according to the Lugano Classification. For patients with splenic MZL this requirement may be restricted to splenomegaly alone since that is usually the only manifestation of measurable disease.
4. Patients affected by WM who do not have at least one bi-dimensionally measurable lesion in the baseline radiologic assessment must have measurable disease, defined as presence of immunoglobulin M (IgM) paraprotein with a minimum IgM level ≥ 2 x upper limit of normal and positive immunofixation test.
5. Male or female patients ≥ 18 years of age
6. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
7. Life expectancy of at least 3 months
8. Availability of fresh tumor tissue and/or archival tumor tissue at Screening
9. Adequate baseline laboratory values as assessed within 7 days before starting study treatment.
10. Left ventricular ejection fraction ≥ 50%
Exclusion Criteria
1. Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed disease, or chronic lymphocytic leukemia. In patients with clinical suspicion of transformed disease, a fresh biopsy is recommended.
2. Rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody (e.g. obinutuzumab) resistance at any line of therapy (resistance defined as lack of response, or progression within 6 months of the last date of rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody administration, including maintenance with these drugs).
3. HbA1c > 8.5% at screening
4. History or concurrent condition of interstitial lung disease and/or severely impaired lung function (as judged by the investigator)
5. Known lymphomatous involvement of the central nervous system
6. Known history of human immunodeficiency virus (HIV) infection
7. Hepatitis B (HBV) or hepatitis C (HCV) infection. Patients positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-DNA, these patients should receive prophylactic antiviral therapy as per rituximab label. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.
8. Cytomegalovirus (CMV) infection. Patients who are CMV PCR positive at baseline will not be eligible.CMV PCR test is considered positive if, the result can be interpreted as a CMV viremia according to local standard of care.
9. Uncontrolled hypertension despite optimal medical management (per investigator´s assessment)
10. Congestive heart failure > New York Heart Association (NYHA) class 2
2. Rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody (e.g. obinutuzumab) resistance at any line of therapy (resistance defined as lack of response, or progression within 6 months of the last date of rituximab, or rituximab biosimilars, or anti-CD20 monoclonal antibody administration, including maintenance with these drugs).
3. HbA1c > 8.5% at screening
4. History or concurrent condition of interstitial lung disease and/or severely impaired lung function (as judged by the investigator)
5. Known lymphomatous involvement of the central nervous system
6. Known history of human immunodeficiency virus (HIV) infection
7. Hepatitis B (HBV) or hepatitis C (HCV) infection. Patients positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) will be eligible if they are negative for HBV-DNA, these patients should receive prophylactic antiviral therapy as per rituximab label. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.
8. Cytomegalovirus (CMV) infection. Patients who are CMV PCR positive at baseline will not be eligible.CMV PCR test is considered positive if, the result can be interpreted as a CMV viremia according to local standard of care.
9. Uncontrolled hypertension despite optimal medical management (per investigator´s assessment)
10. Congestive heart failure > New York Heart Association (NYHA) class 2
The Estimated Number of Participants
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Taiwan
14 participants
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Global
727 participants
