The main goal of this study is to determine the Maximum Tolerated Dose (MTD) and the Recommended Phase II Dose (RP2D) as well as preliminary antitumor activity of bimiralisib (PQR309) administered orally, as once daily capsules continuously and on intermittent schedule in patients with relapsed or refractory lymphomas.
Open-label, non-randomized, multicentre phase 2 study with a safety run-in evaluating efficacy and safety of bimiralisib (PQR309) in patients with relapsed or refractory lymphoma. The maximum tolerated dose (MTD) of bimiralisib in patients with advanced solid tumors was defined as 80 mg once daily given continuously (q.d. schedule) in a previous phase 1 study. The safety run-in of this study will follow a modified 3 + 3 design to evaluate the safety of 60 and 80 mg bimiralisib in patients with relapsed or refractory lymphoma administered p.o. once daily during a DLT (dose-limiting toxicity) period of 28 days. In the safety run-in, three patients will be treated at 60 mg bimiralisib for 28 days. Enrollment and treatment of all three patients may occur simultaneously as 80 mg bimiralisib p.o. qd was established as the MTD in solid tumors. Unless a DLT is observed in any of the three patients during the first 28 days of treatment, the investigators and the sponsor will decide to escalate the dose to 80 mg. Intermittent dosing schedules may be evaluated if, based on the overall evaluation of all the clinical and PK (pharmacokinetic) data from this and other studies with bimiralisib, data emerge during step 1 of the phase 2 expansion in this study, indicating that daily dosing of bimiralisib is not adequately tolerated or inefficacious.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
53
60 mg or 80 mg bimiralisib per oral (p.o.) once daily or intermittent dosing (120mg,140mg and 160mg) until unacceptable AE, disease progression, patient's request for withdrawal, investigator judgement or death - whichever comes first.
Weill Cornell Medicine
New York, New York, United States
University Clinical Center Republic of Srpska
Banja Luka, Bosnia and Herzegovina
University Clinical Center Sarajevo
Sarajevo, Bosnia and Herzegovina
Assessment of Change of Tumor Response Criteria in lymphoma patients During Treatment with PQR309 in patients with relapsed or refractory lymphoma according to Cheston Criteria (5)
Radiological lymphoma Evaluation (CT or other indicated according to institutional standard practice), clinical examination and bone marrow biopsy
Time frame: 28 day prior to first treatment (baseline), during treatment every 8 weeks during 6 months and every 6 months afterwards up to 1 year)
Incidence of serious adverse events (SAE) and severity of all adverse events (AEs)
Continuous dosing and intermittent dosing
Time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, at the end of treatment up to 1 year and 30 days after last dose
Change of pulse rate
Continuous dosing and intermittent dosing
Time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, at the end of treatment up to 1 year and 30 days after last dose
Change in blood pressure
Continuous dosing and intermittent dosing
Time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose
Change in body temperature
Continuous dosing and intermittent dosing
Time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose
Change in ECOG (Eastern Cooperative Oncology Group) Performance status
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Insitute Curie
Saint-Cloud, Paris, France
Univeristy Hospital Haifa
Haifa, Israel
Institute for Oncology and radiology of Serbia
Belgrade, Serbia
Clinical Center Kragujevac
Kragujevac, Serbia
Clinical Center Nis
Niš, Serbia
Guy's Hospital
London, United Kingdom
Royal Marsden NHS Foundation Trust
London, United Kingdom
...and 2 more locations
Continuous dosing and intermittent dosing
Time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose
Change in body weight
Continuous dosing and intermittent dosing
Time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose
Change in haematology
Continuous dosing and intermittent dosing
Time frame: Before treatment on Day -1,-2 and during treatment on Day 1,2,8,15,22,36,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year and 30 days after last dose
Change in blood chemistry
Continuous dosing and intermittent dosing
Time frame: Before treatment on Day -1 and during treatment on Day 1,22,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year
Change in ECG (electrocardiogram)
Continuous dosing and intermittent dosing
Time frame: Before treatment on Day -1 and during treatment on Day 1,22,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year
Change of urine analysis
Continuous dosing and intermittent dosing
Time frame: Before treatment on Day -1 and during treatment on Day 1,22,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year
Change in HbA1c
Continuous dosing and intermittent dosing
Time frame: Before treatment on Day -1 and during treatment on Day 1,22,50, subsequently every 4 weeks up to 1 year, at the end of treatment up to 1 year
Change in tmax
Continuous dosing and intermittent dosing
Time frame: During treatment on Day 1,2, 8,15 22, 50
Change in Cmax
Continuous dosing and intermittent dosing
Time frame: During treatment on Day 1,2, 8,15 22, 50
Change in AUC 0-24
Continuous dosing and intermittent dosing
Time frame: During treatment on Day 1,2, 8,15 22, 50
Change in AUClast
Continuous dosing and intermittent dosing
Time frame: During treatment on Day 1,2, 8,15 22, 50
Change in AUC0-∞,
Continuous dosing and intermittent dosing
Time frame: During treatment on Day 1,2, 8,15 22, 50
Change in t1/2
Continuous dosing and intermittent dosing
Time frame: During treatment on Day 1,2, 8,15 22, 50
Change in RAC
Continuous dosing and intermittent dosing
Time frame: During treatment on Day 1,2, 8,15 22, 50