Phase III Copanlisib in Rituximab-refractory iNHL
Condition: Lymphoma, Non-Hodgkin
MeSH terms: Lymphoma; Lymphoma, Non-Hodgkin
Intervention: Copanlisib (BAY 80-6946)
Intervention description: 60 mg of experimental drug in solution administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 25.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: indolent Non-Hodgkin lymphoma; rituximab-refractory

Summary:

      To assess the safety of copanlisib.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed diagnosis of indolent B-cell NHL, with histological subtype
             limited to the following:

               -  Follicular lymphoma (FL) grade 1-2-3a.

               -  Small lymphocytic lymphoma (SLL) with absolute lymphocyte count < 5 x 10*9/L at
                  the time of diagnosis and at study entry.

               -  Lymphoplasmacytoid lymphoma/Waldenström macroglobulinemia (LPL/WM).

               -  Marginal zone lymphoma (MZL) (splenic, nodal, or extra-nodal).

          -  Patients must have received two or more prior lines of treatment. A previous regimen
             is defined as one of the following: at least two months of single-agent therapy, at
             least two consecutive cycles of polychemotherapy, autologous transplant,
             radioimmunotherapy.

          -  Prior therapy must include rituximab and alkylating agents.Prior exposure to
             idelalisib or other PI3K inhibitors is acceptable (except to copanlisib) provided that
             there is no resistance.

          -  Patients must be refractory to the last rituximab-based treatment, defined as no
             response or response lasting < 6 months after completion of treatment. Time interval
             to assess refractoriness will be calculated between the end date (last day) of the
             last rituximab-containing regimen and the day of diagnosis confirmation of the
             subsequent relapse.

          -  Patients must have at least one bi-dimensionally measurable lesion (which has not been
             previously irradiated) according to the Recommendations for Initial Evaluation,
             Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: 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.

          -  ECOG performance status ≤ 1

          -  Adequate bone marrow, liver and renal function

        Exclusion Criteria:

          -  Histologically confirmed diagnosis of FL grade 3b.

          -  Chronic lymphocytic leukemia (CLL).

          -  Transformed disease (assessed by investigator):

               -  histological confirmation of transformation, or

               -  clinical and laboratory signs: rapid disease progression, high standardized
                  uptake value (SUV) (> 12) by positron emission tomography (PET) at baseline if
                  PET scans are performed (optional).

          -  Bulky disease - Lymph nodes or tumor mass (except spleen) >= 7cm LD (longest diameter)

          -  Known lymphomatous involvement of the central nervous system.

          -  Uncontrolled arterial hypertension despite optimal medical management (per
             investigator's assessment).

          -  Type I or II diabetes mellitus with HbA1c > 8.5% at Screening.

          -  Known history of human immunodeficiency virus (HIV) infection.

          -  Active clinically serious infections > CTCAE Grade 2

          -  Active Hepatitis B or hepatitis C

          -  History or concurrent condition of interstitial lung disease of any severity and/or
             severely impaired lung function (as judged by the investigator)

          -  History of having received an allogeneic bone marrow or organ transplant

          -  Positive cytomegalovirus (CMV) PCR test at baseline

          -  Pregnant or breast-feeding patients