CompletedNCT02249429Updated Sep 6, 2019

Open-Label, Non Randomized Phase 2 Study With Safety Run-In

A Phase 2 interventional study of bimiralisib in Lymphoma, Malignant, sponsored by PIQUR Therapeutics AG. Completed at 12 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-09-06.

Sponsored by PIQUR Therapeutics AG · Phase 2, Interventional, and Treatment

From the registry’s dates

Primary completion was Sep 2018, 8 years ago, and no results have been posted to the registry; the sponsor requested a delay in submitting them in Aug 2019.

Phase: Phase 2
Study type: Interventional
Enrollment: 53
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study summary

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.

Read the detailed description

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.

Conditions studied

Lymphoma, Malignant

Browse trials for

Lymphoma 5,577

Keywords

Non Hodgkin Lymphoma

In context

Lymphoma

5,577 studies on the registry are indexed under Lymphoma; 824 are open to participants now.

This study's enrollment of 53 is above the median of 40 across 4,507 interventional studies indexed under Lymphoma.

Browse Lymphoma studies →

Lead sponsor

PIQUR Therapeutics AG is the lead sponsor of 6 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Histologically confirmed diagnosis* of relapsed or refractory lymphoma, received at least two prior lines of therapy including immuno-chemotherapy. Patients with relapsed Chronic Lymphoid Leukemia (CLL) are eligible if they have received one or more prior lines of any approved standard therapy. * archival biopsies may be used if obtained up to a year prior to enrollment; re-biopsy is strongly recommended if last biopsy was obtained more than a year ago.
Only for patients in the Phase 2 part: At least one measurable nodal or extra-nodal lesion defined as follows: Clearly measurable (i.e. well-defined boundaries) in at least two perpendicular dimensions on imaging scan with > 1.5 cm in longest transverse diameter.
Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-1 (See Appendix 2).
Adequate organ system functions defined as:
1. Absolute neutrophil count (ANC) ≥1.0x109/l
2. Platelets ≥ 75x109/l
3. Haemoglobin ≥ 85g/L
4. Adequate hepatic function, defined as Total bilirubin ≤ 1.5 times the upper limit of normal (ULN) and Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times ULN (or ALT/AST ≤ 5 times ULN in patients with liver involvement)
5. Adequate renal function, defined as serum creatinine ≤ 1.5 times ULN
6. Fasting glucose \< 7.0 mmol/L; Glycated haemoglobin (HbA1c) \< 6.4%
Ability and willingness to swallow and retain oral medication.
Willingness and ability to comply with the trial procedures
Female and male patients with reproductive potential must agree to use effective contraception from screening until 90 days after discontinuation of PQR309
Signed informed consent

Exclusion criteria

Exclusion Criteria:

Any of the following conditions precludes enrollment of a patient:

Immunosuppression due to:
- Allogeneic hematopoietic stem cell transplant (HSCT)
- Any immune-suppressive therapy within 4 weeks prior to trial treatment start
- Known HIV infection
Autologous stem cell transplant within 3 months prior to trial treatment start.
Concomitant anticancer therapy (e.g. chemotherapy, radiotherapy, hormonal therapy, immunotherapy, biological response modifier, signal transduction inhibitors).
Concomitant treatment with medicinal products that increase the pH (reduce acidity) of the upper gastrointestinal tract, including, but not limited to, proton-pump inhibitors (e.g. omeprazole), H2-antagonists (e.g. ranitidine) and antacids. Patients may be enrolled in the study after a wash-out period sufficient to terminate their effect.
Use of any investigational drug within 21 days prior to trial treatment start.
Patients who experienced National Cancer Institute (NCI) Common Terminology Criteria For Adverse Events (CTCAE) ≥ Grade 3 on PI3K/mTOR inhibitors
Any major surgery, chemotherapy or immunotherapy within 21 days prior to trial treatment start.
Symptomatic or progressing Central nervous system (CNS) involvement. Exception: Patients with meningeal involvement can be included upon discussion between the sponsor and the investigator.
Persisting toxicities NCI CTCAE ≥2 related to prior anticancer therapy
Presence of gastrointestinal disease or any other condition that could interfere significantly with the absorption of the study drug.
Severe/unstable angina, myocardial infarction or coronary artery bypass within the last 3 years prior to trial treatment start, symptomatic congestive heart failure New York Heart Association (NYHA) Class 3 or 4, hypertension BP>150/100mmHg
A serious active infection at the time of treatment, or another serious underlying medical condition that could impair the ability of the patient to receive treatment.
Lack of appropriate contraceptive measures (male and female)
Pregnant or lactating women
Known HIV infection
Significant medical conditions which could jeopardize compliance with the protocol.
Uncontrolled diabetes mellitus; patients with controlled diabetes may be enrolled (see fasting glucose and HbA1c levels in inclusion criteria).

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 53 participants (actual)

Study arms

Experimental
bimiralisib (PQR309)
Drug: bimiralisib

Interventions

Drugbimiralisib
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.
Also known as: PQR309, PI3K Inhibitor (phosphatidylinositol 3-kinase)

What researchers measure

Primary outcomes

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)

Secondary outcomes

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
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

Other outcomes

Change in insulin/ C-Peptide/ glucose
Continuous dosing and intermittent dosing
Time frame: During treatment on Day 1,2, 8,15 22, 50

Study locations

12 sites

Weill Cornell Medicine
New York, New York 10065, United States
University Clinical Center Republic of Srpska
Banja Luka, 78000, Bosnia and Herzegovina
University Clinical Center Sarajevo
Sarajevo, 71000, Bosnia and Herzegovina
Insitute Curie
Saint-Cloud, Paris 92210, France
Univeristy Hospital Haifa
Haifa, Israel
Institute for Oncology and radiology of Serbia
Belgrade, 110000, Serbia
Clinical Center Kragujevac
Kragujevac, 34000, Serbia
Clinical Center Nis
Nis, 118000, Serbia
Guy's Hospital
London, SE1 9RT, United Kingdom
Royal Marsden NHS Foundation Trust
London, United Kingdom
University College Hospital London
London, United Kingdom
Churchill Hospital
Oxford, OX3 7DQ, United Kingdom

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Sep 6, 2019, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02249429
Lead sponsor: PIQUR Therapeutics AG
Collaborators: University College London Hospitals, Churchill Hospital, Royal Marsden NHS Foundation Trust, University of Haifa, Weill Medical College of Cornell University, Institut Curie, University Clinical Center, Sarajevo, Clinical Center Kragujevac, Clinical Center Nis, Nis, Institute for Oncology and Radiology Serbia, Belgrade, University Clinical Centre of Republic of Srpska
Responsible party: Sponsor
First posted: Sep 25, 2014
Start date: May 2015
Primary completion: Sep 11, 2018
Completion: Sep 11, 2018
Last update: Sep 6, 2019

Study contacts

Rakesh Popat

principal investigator · Univeristy College London

David Cunningham

principal investigator · Royal Marsden NHS Foundation Trust

Paul Fields

principal investigator · Guy's Hospital

Graham Collins

principal investigator · Churchill Hospital

Netanel Horowitz

principal investigator · University of Haifa

Giulino Roth

principal investigator · Weill Cornell Medicine New York

Carole Soussain

principal investigator · Curie Institute

Sinisa Radulovic

principal investigator · Institute for Oncology and Radiology Serbia

Ivan Tijanic

principal investigator · Clinical Center Nis

Nebojsa Andjelkovic

principal investigator · Clinical Center Kragujevac

Sabrina Kurtovic

principal investigator · University Clinical Center, Sarajevo

Danijela Mandic

principal investigator · University Clinical Centre of Republic of Srpska

Oversight

Data monitoring committee: No
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Aug 2019. You cannot join it, but the record below documents what was studied.

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