Phase III Copanlisib in Rituximab-refractory iNHL

Study Overview
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Brief Summary
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To assess the safety of copanlisib.

Official Title
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A Randomized, Double-blind Phase III Study of Copanlisib Versus Placebo in Patients With Rituximab-refractory Indolent Non-Hodgkin's Lymphoma (iNHL) - CHRONOS-2

Conditions
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Lymphoma, Non-Hodgkin

Intervention / Treatment
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* Drug: Copanlisib (BAY 80-6946)


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Copanlisib (BAY 80-6946)<br>patients with rituximab-refractory iNHL | Drug: Copanlisib (BAY 80-6946)<br>* 60 mg of experimental drug in solution administered intravenously on Days 1, 8 and 15 of each 28-day treatment cycle<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-emergent Adverse Events (TEAE)s | Adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up) | up to 7 years | 
| Number of Participants With Treatment-emergent Serious Adverse Events (TESAE)s | Serious adverse event data were collected after signing the informed consent until 30 days after the last study drug administration (end of safety follow-up) | up to 7 years | 
| Number of Participants With Abnormal Laboratory Parameters | - Above threshold of 10% and reported as TEAEs - any event (Grade 1-4) | up to 7 years | 
| Number of Participants With Abnormal Vital Signs | - Reported as TEAEs - worst CTCAE grade total - | up to 7 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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indolent Non-Hodgkin lymphoma, rituximab-refractory