Phase III study of copanlisib with standard immunochemotherapy in relapsed iNH
- Conditions
- ymphoma, Non-Hodgkin
- Registration Number
- JPRN-jRCT2080223744
- Lead Sponsor
- Bayer Yakuhin, Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- completed
- Sex
- All
- Target Recruitment
- 52
Histologically confirmed diagnosis of CD20 positive iNHL with histological subtype limited to:
- Follicular lymphoma G1-2-3a
Small lymphocytic lymphoma with absolute lymphocyte count < 5x10E9/L at study entry
- Lymphoplasmacytoid lymphoma/Waldenstrom macroglobulinemia (LPL/WM)
- Marginal zone lymphoma (splenic, nodal, or extra-nodal)
- Patients must have relapsed after at least 1 but at most 3 prior lines of therapy, including rituximab and alkylating agents. A previous regimen is defined as one of the following: at least 2 months of single-agent therapy; at least 2 consecutive cyclesof polychemotherapy; autologous transplant; radioimmunotherapy. Previous exposure to other PI3Ki is acceptable provided there is no resistance.
- Non-WM must have at least one bi-dimensionally measurable lesion (that has not been previously irradiated) according to the Lugano Classification.
- 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 (ULN) and positive immunofixation test.
- Male or female patients >= 18 years of age
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Life expectancy of at least 3 months
- Availability of fresh tumor tissue and/or archival tumor tissue at Screening
- Adequate baseline laboratory values collected within 7 days of starting the study treatment
- Left ventricular ejection fraction (LVEF) >= 50%
- Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed disease, or chronic lymphocytic leukemia.
- Rituximab resistance at any line of therapy (resistance defined as lack of response, or progression within 6 months of the last course of treatment with a rituximab containing regimen)
- History or concurrent condition of interstitial lung disease and/or severely impaired lung function (as judged by the investigator)
- Known lymphomatous involvement of the central nervous system
- HbA1c > 8.5% at Screening
- Known history of human immunodeficiency virus (HIV) infection
- 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. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.
- Uncontrolled hypertension despite optimal medical management (per investigators assessment)
- Histologically confirmed diagnosis of follicular lymphoma grade 3b or transformed disease, or chronic lymphocytic leukemia.
- Rituximab resistance at any line of therapy (resistance defined as lack of response, or progression within 6 months of the last course of treatment with a rituximab containing regimen)
- History or concurrent condition of interstitial lung disease and/or severely impaired lung function (as judged by the investigator)
- Known lymphomatous involvement of the central nervous system
- HbA1c > 8.5% at Screening
- Known history of human immunodeficiency virus (HIV) infection
- 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. Patients positive for anti-HCV antibody will be eligible if they are negative for HCV-RNA.
- Uncontrolled hypertension despite optimal medical management (per investigators assessment)
- Congestive heart failure > New York Heart Association (NYHA) class 2
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method safety<br>efficacy<br>pharmacokinetics<br>- Evaluation whether copanlisib in combination with standard immunochemotherapy, is superior to placebo and standard immunochemotherapy assessed by the prolongation of progression free survival (PFS) - applicable to Phase III part<br>- 53 months
- Secondary Outcome Measures
Name Time Method safety<br>efficacy<br>pharmacokinetics<br>other<br>- Objective tumor response rate (ORR)<br>- Duration of tumor response (DOR)<br>- Complete tumor response rate (CRR)<br>- Time to tumor progression (TTP)<br>- Time to next anti-lymphoma treatment (TTNT)<br>- Overall survival (OS)<br>- Number of participants with adverse events as a measure of safety and tolerability<br>- Physical (DRS-P) will be assessed using the NCCN-FACT Lymphoma Symptom Index-18 (FLymSI-18) questionnaire<br>- 53 months