Conditions: Lymphoma, Non-Hodgkin
Keywords: Clinical trial, phase II Phosphatidylinositol 3-Kinase Class I, Non-Hodgkin's lymphoma
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 227
Healthy volunteers: no

Brief summary:
The objective of the study (part A) is to evaluate the efficacy and safety of BAY80-6946 in patients with indolent or aggressive Non-Hodgkin's Lymphoma, who have progressed after standard therapy. 30 patients will be enrolled to both indolent and aggressive disease group. The objective of the study part B (CHRONOS-1) is to evaluate the efficacy and safety of BAY80-6946 in patients with relapsed/refractory follicular lymphoma. 120 patients will be enrolled in the part B of the study. Further objectives are to evaluate the pharmacokinetics and biomarkers. Quality of life will be a further objective of part B of the study.

In a cohort of 20 patients (enrolled both in part A and B) an ECG substudy will be performed to assess the potential for cardiac toxicity and QT/QTc interval prolongation of BAY80-6946.

After an up to 28-day screening period, eligible patients will start treatment with BAY80-6946 at a dose of 0.8 mg/kg (Part A) and at a dose of 60 mg (Part B).

Treatment will be continued until disease has progressed or until another criterion is met for withdrawal from study. An end-of-treatment visit will be performed within 7 days after discontinuation of study treatment. Thirty to 35 days after last study drug administration, a safety followup visit will be performed for the collection of adverse events (AEs) and concomitant medication data. Patients will be contacted quarterly to determine overall survival status up to 4 years after last patient completed treatment. Patients who discontinue study drug for reasons other than disease progression will enter the Active Assessment Follow-up period. The end of study notification to Health Authorities will be based on the completion of the collection of survival data.

The efficacy is measured by the decrease in tumor size. Tumor assessments will be done at Screening, every 8 weeks during Year 1, every 12 weeks during Year 2, and every 6 months during Year 3. Blood samples will be collected for pharmacokinetic analysis. Archival tumor tissue and blood samples will be collected for biomarker analysis (mandatory) and for central pathology review (part B), fresh biopsy tissue will also be collected if available.

Detailed description:

Arms:
arm 1: Part A: Participants in this arm will be patients with indolent NHL. arm 2: Part A: Participants in this arm will be patients with aggressive NHL. arm 3: Part B: Participants in this arm will be patients with indolent B-cell NHL.

Interventions: intervention 1: Copanlisib (Aliqopa, BAY80-6946)
Intervention descriptions: intervention 1: BAY 80-6946 is administered in a normal saline solution, 100 mL, intravenously over 1h. No intravenous glucose preparations should be administered on the days of infusion. Dosing is weekly for the first 3 weeks (on Days 1, 8, and 15) of a 28-day cycle, followed by a 1-week break (i.e., no infusion on Day 22).

Part A: The individual dose will be 0.8 mg/kg (max. 65 mg) per infusion from Cycle 1 on. The maximum dose of 65 mg should never be exceeded.

Part B: The individual dose will be 60 mg per infusion from Cycle 1 on.

Protocol document: