PQR309 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma

NCT02669511 | Completed Phase 2 FDA Drug

• 1 other identifier: PQR309-005
• Study Type: interventional
• Target: 21
• Locations: 0 countries
• Sites: N/A

Brief Summary

An open-label, non-randomized, two-stage, multicenter study evaluating clinical efficacy, safety and pharmacokinetics of PQR309 in patients with relapsed or refractory Primary Central Nervous System Lymphoma (PCNSL).

Conditions

Primary Central Nervous System Lymphoma

Keywords

DLBCL

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR including complete response (CR, unconfirmed complete(CRu) and partial response (PR) according to the 2005 Response Criteria of the Central Nervous System (CNS) Lymphoma Collaborative Group (IPCG)

  Every 8 weeks up to 6 months

Secondary Outcomes (14)

• Number of adverse events (AE) as related to the study medication.

  Week 1 Day 1 to 30 days after last dose up to 12 months

• Changes in puls rate

  Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose

• Changes in blood pressure

  Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose

• Changes in body weight

  Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose

• Changes in temperature

  Week 1 Day 1 prior to treatment, Treatment on Day 8,Day 15 and 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose

Study Arms (1)

PQR309

OTHER

A single arm study with PQR309, a phosphoinositide-3-kinases (PI3K) and inhibitor of the mammalian target of rapamycin (mTOR), 60mg/80mg given once a day, orally.

Drug: PQR309

Interventions

PQR309 DRUG

Oral PQR309, 80mg or 60mg daily or intermittent dosing

Also known as: bimiralisib

PQR309

Eligibility Criteria

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

You may qualify if:

• ≥18 years of age.
• Patient with histologically/cytologically confirmed Primary Central Nervous System Lymphoma (PCNSL)
• Relapsed or refractory Primary Central Nervous System Lymphoma (PCNSL) demonstrated by cranial MRI.
• Presence of at least one lesion of bi-dimensionally measurable disease on baseline
• MRI with a contrast-enhancing tumor of at least 1 cm (10 mm) in the longest diameter.
• Maximum one prior systemic therapy regimen.
• If receiving corticosteroids, patients must have been on a stable or decreasing dose of corticosteroids and no more than 8 mg dexamethasone (or equivalent) for at least 5 days prior to date of enrollment.
• Karnofsky Performance Score (KPS) ≥ 70%.
• More than 4 weeks from any investigational agent.
• Adequate haematological, liver and renal function
• Able and willing to swallow and retain oral medication.
• Female and male patients of reproductive potential must agree to use effective contraception from screening until 90 days after discontinuing study treatment.
• Willing and able to sign the informed consent and to comply with the protocol for the duration of the study.

You may not qualify if:

• Central Nervous System (CNS) Lymphoma or chronic immunosuppression-associated central nervous system (CNS) lymphoma.
• Previous allogeneic hematopoietic stem cell transplant (HSCT transplant).
• Previous whole brain radiotherapy (WBRT)
• Other concomitant anti-tumor therapy as determined by the study team.
• Patients unable to undergo contrast-enhanced MRI.
• Prior treatment with a phosphoinositide -3 kinase (PI3K) inhibitor, Protein Kinase B Inhibitor is known as AKT inhibitor, or mammalian target of rapamycin (mTOR) inhibitor.
• Patient taking enzyme-inducing anti-epileptic drug (EIAED) \< 7 days of the first dose of PQR309.
• Patient is taking a drug with a risk to promote QT prolongation and Torsades de Pointes.
• Patient is currently using herbal preparations or medications. Patient should stop using herbal medications 7 days prior to the first dose of the study drug.
• Medically documented history of or active major depressive episode, bipolar disorder (I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or patients with active severe personality disorders.
• Anxiety ≥ Common Terminology Criteria (CTC) of adverse events (AE) grade 3.
• Patient has an uncontrolled intercurrent illness, including, but not limited to, ongoing or active infection, HIV infection, chronic liver disease.
• chronic renal disease, pancreatitis, chronic pulmonary disease, active cardiac disease or cardiac dysfunction, interstitial lung disease, active autoimmune disease, uncontrolled diabetes, neuropsychiatric or social situations that would limit compliance with the study requirements.
• Presence of gastrointestinal disease or any other condition that could interfere significantly with the absorption of the study drug.
• Concomitant treatment with medicinal products that increase the potential hydrogen (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 washout period sufficient to terminate their effect.

Sponsors & Collaborators

• PIQUR Therapeutics AG: lead

Study Officials

• Agnieszka Korfel, MD

  Charite-Universitaetsmedizin Berlin (Germany)

  PRINCIPAL INVESTIGATOR

• Uwe Schlegel, Prof

  Neurologische UniversitätsklinikKnappschaftskrankenhaus Bochum GmbH

  PRINCIPAL INVESTIGATOR

• Elisabeth Schorb, MD

  UNIVERSITÄTSKLINIKUM FREIBURGKlinik für Innere Medizin I

  PRINCIPAL INVESTIGATOR

• Martin Dreyling, Prof

  Medizinische Klinik und Poliklinik III Klinikum der Universität München

  PRINCIPAL INVESTIGATOR

• Gerald Illerhaus, Prof

  Klinik für Hämatologie, Onkologie und PalliativmedizinStuttgart Cancer

  PRINCIPAL INVESTIGATOR

• Michael Weller, Prof

  University of Zurich

  PRINCIPAL INVESTIGATOR

• Daniela Bota, MD

  Center101 The City Drive SouthOrange, CA 92686

  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: January 7, 2016
• First Posted: February 1, 2016
• Study Start: November 12, 2015
• Primary Completion: January 12, 2018
• Study Completion: January 12, 2018
• Last Updated: July 9, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share