Patients with relapsed indolent non-Hodgkin's lymphoma MedDRA version: 23.0 Level: PT Classification code 10029600 Term: Non-Hodgkin's lymphoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Bayer AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Main criteria for inclusion: -Histologically confirmed diagnosis of CD20 positive iNHL with histological subtype limited to: o Follicular lymphoma (FL) G1, G2, or G3a o Small lymphocytic lymphoma (SLL) with absolute lymphocyte count =65 years) yes F.1.3.1 Number of subjects for this age range 260
Exclusion criteria
Exclusion criteria: - Histologically confirmed diagnosis of follicular lymphoma (FL) grade 3b or transformed disease, or chronic lymphocytic leukemia. In patients with clinical suspicion of transformed disease, a fresh biopsy is recommended. - 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 ). - HbA1c > 8.5% at Screening. - 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. - Known history of human immunodeficiency virus (HIV) infection. - Hepatitis B (HBV) or 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. - 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 SOC. - Congestive heart failure > New York Heart Association (NYHA) class 2. - Uncontrolled hypertension despite optimal medical management (per investigator’s assessment).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Safety run-in part: Primary objective is to determine: The recommended phase III dose (RP3D) of copanlisib in combination with standard immunochemotherapy (rituximab and bendamustine [RB] or rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone [R-CHOP]) to be used in the subsequent phase III part of the study Phase III part (randomized, controlled trial) Primary objective is: To evaluate whether copanlisib in combination with standard immunochemotherapy, is superior to standard immunochemotherapy in prolonging progression-free survival (PFS), in patients with relapsed indolent non-Hodgkin’s lymphoma, who have received at least one, but at most three lines of treatment, including rituximab, and/or rituximab biosimilars, and/or anti-CD20 monoclonal antibody-based immunochemotherapy and alkylating agents, and for whom the combination of rituximab with either bendamustine or CHOP represents a valid therapeutic option;Secondary Objective: Safety run-in part The secondary objectives are to evaluate (for patients that stay on treatment after Cycle 1): Radiological and clinical indicators of treatment efficacy Safety and tolerability of copanlisib in combination with R-B/R-CHOP Phase III part (randomized, controlled trial) Secondary objectives are to evaluate: Other radiological and clinical indicators of treatment efficacy (objective response rate (ORR), duration of response (DOR), complete response rate (CRR), time to progression (TTP), time to next antilymphoma treatment (TTNT), disease control rate (DCR), overall survival (OS, 5 year survival rate), time to improvement and the time to deterioration in diseaserelated symptoms - physical) Safety and tolerability of copanlisib in combination with R-B/R-CHOP;Primary end point(s): The primary completion event for this study is PFS (progression assessed by central review or death from any cause if death occurs before progression). The analysis will be performed when approximately 280 PFS even | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy variables are objective response rate (ORR), duration of response (DOR), complete response rate (CRR), time to progression (TTP), time to next anti-lymphoma treatment (TTNT), disease control rate (DCR), overall survival (OS, 5 year survival rate), time to improvement and the time to deterioration in disease-related symptoms - physical (DRS-P) of at least 3 points of lymphoma as measured by the FLymSI-18 questionnaire (FLymSI = NCCN-FACT Lymphoma Symptom Index).;Timepoint(s) of evaluation of this end point: All secondary efficacy endpoints will be analyzed in the FAS at the time of the analysis of the primary efficacy endpoint. Depending on study success in the primary efficacy variable in the FAS, the secondary efficacy variables ORR, time to deterioration and time to improvement in DRS-P subscale of FLymSI-18 of at least 3 points will be tested hierarchically in the FAS. ORR will be tested first and, if successful, will be followed by time to deterioration in DRS-P, and finally, if all previous tests are successful, will be followed by time to improvement of DRS-P and OS. | — |
Countries
Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Czechia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hong Kong, Hungary, Ireland, Israel, Italy, Japan, Korea, Republic of, Mexico, Poland, Portugal, Romania, Russian Federation, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactBayer Clinical Trials Contact
Bayer AG
Outcome results
None listed