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

NCT02249429 | Completed Phase 2 FDA Drug

• 1 other identifier: PQR309-002
• Study Type: interventional
• Target: 53
• Locations: 6 countries
• Sites: 12

Brief 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.

Conditions

Lymphoma, Malignant

Keywords

Non Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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

  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 (18)

• Incidence of serious adverse events (SAE) and severity of all adverse events (AEs)

  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

  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

  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

  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

  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

Other Outcomes (1)

• Change in insulin/ C-Peptide/ glucose

  During treatment on Day 1,2, 8,15 22, 50

Study Arms (1)

bimiralisib (PQR309)

EXPERIMENTAL

Drug: bimiralisib

Interventions

bimiralisib DRUG

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)

bimiralisib (PQR309)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Absolute neutrophil count (ANC) ≥1.0x109/l
• Platelets ≥ 75x109/l
• Haemoglobin ≥ 85g/L
• 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)
• Adequate renal function, defined as serum creatinine ≤ 1.5 times ULN
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• PIQUR Therapeutics AG: lead
• University College London Hospitals: collaborator
• Churchill Hospital: collaborator
• Royal Marsden NHS Foundation Trust: collaborator
• University of Haifa: collaborator
• Weill Medical College of Cornell University: collaborator
• Institut Curie: collaborator
• University Clinical Center, Sarajevo: collaborator
• Clinical Center Kragujevac: collaborator
• Clinical Center Nis, Nis: collaborator
• Institute for Oncology and Radiology Serbia, Belgrade: collaborator
• University Clinical Centre of Republic of Srpska: collaborator

Study Sites (12)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

University Clinical Center Republic of Srpska

Banja Luka, 78000, Bosnia and Herzegovina

Location

University Clinical Center Sarajevo

Sarajevo, 71000, Bosnia and Herzegovina

Location

Insitute Curie

Saint-Cloud, Paris, 92210, France

Location

Univeristy Hospital Haifa

Haifa, Israel

Location

Institute for Oncology and radiology of Serbia

Belgrade, 110000, Serbia

Location

Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

Clinical Center Nis

Niš, 118000, Serbia

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

Royal Marsden NHS Foundation Trust

London, United Kingdom

Location

University College Hospital London

London, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7DQ, United Kingdom

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, Non-Hodgkin

Interventions

Phosphatidylinositol 3-Kinase

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphatidylinositol 3-Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Proteins; Amino Acids, Peptides, and Proteins

Study Officials

• Rakesh Popat

  Univeristy College London

  PRINCIPAL INVESTIGATOR

• David Cunningham

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• Paul Fields

  Guy's Hospital

  PRINCIPAL INVESTIGATOR

• Graham Collins

  Churchill Hospital

  PRINCIPAL INVESTIGATOR

• Netanel Horowitz

  University of Haifa

  PRINCIPAL INVESTIGATOR

• Giulino Roth

  Weill Cornell Medicine New York

  PRINCIPAL INVESTIGATOR

• Carole Soussain

  Curie Institute

  PRINCIPAL INVESTIGATOR

• Sinisa Radulovic

  Institute for Oncology and Radiology Serbia

  PRINCIPAL INVESTIGATOR

• Ivan Tijanic

  Clinical Center Nis

  PRINCIPAL INVESTIGATOR

• Nebojsa Andjelkovic

  Clinical Center Kragujevac

  PRINCIPAL INVESTIGATOR

• Sabrina Kurtovic

  University Clinical Center, Sarajevo

  PRINCIPAL INVESTIGATOR

• Danijela Mandic

  University Clinical Centre of Republic of Srpska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 8, 2014
• First Posted: September 25, 2014
• Study Start: May 1, 2015
• Primary Completion: September 11, 2018
• Study Completion: September 11, 2018
• Last Updated: September 6, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

SE (3); GB (4); FR (1); US (1); IL (1); BO (2)