phase iii copanlisib in rituximab-refractory inhl

Conditions: Lymphoma, Non-Hodgkin

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

Keywords: indolent non-hodgkin lymphoma rituximab-refractory