Phase III Copanlisib in Rituximab-refractory iNHL

• Status: Active, not recruiting
• Trial end date: 2021-11-30
• Target enrollment: 0
• Participant gender: All

Summary

To assess the safety of copanlisib.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bayer
• Treatments: Pharmaceutical Solutions; Rituximab

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