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

July 3, 2019 updated by: PIQUR Therapeutics AG

Open-label, Non-randomized, Phase 2 Study Evaluating Efficacy and Safety of PQR309 in Patients With Relapsed or Refractory Primary Central Nervous System Lymphoma

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).

Study Overview

Status

Completed

Intervention / Treatment

Detailed Description

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

The first stage of the study will enroll a minimum of 12 patients with relapsed or refractory Primary Central Nervous System Lymphoma (PCNSL) evaluable for the primary study objective. If during the first stage of the study data emerge that 80 mg p.o. qd is not adequately tolerated or is inefficacious in patients with relapsed or refractory Primary Central Nervous System Lymphoma (PCNSL), additional patients may be enrolled in the study to evaluate alternative dosing regimens, either a lower daily dose (eg. 60 mg) or a lower weekly dose with administration on 2 consecutive days followed by 5 days without treatment in 7-day treatment cycles (intermittent dosing schedule A).In all cases data from at least 12 evaluable patients will be required on the selected dosing regimen (daily or weekly) before the decision is made to proceed with this regimen into the second stage of the study.Nine (9) additional patients will be enrolled for the second stage of the study, for a minimum of 21 patients on the selected dosing regimen in total, evaluable for the final primary endpoint analysis.All patients evaluable for the primary endpoint will be followed until disease progression or death.

Secondary objectives, PQR309 treatment safety and pharmacokinetics (PK) will be evaluated in all enrolled patients in both study stages.

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. ≥18 years of age.
  2. Patient with histologically/cytologically confirmed Primary Central Nervous System Lymphoma (PCNSL)
  3. Relapsed or refractory Primary Central Nervous System Lymphoma (PCNSL) demonstrated by cranial MRI.
  4. Presence of at least one lesion of bi-dimensionally measurable disease on baseline
  5. MRI with a contrast-enhancing tumor of at least 1 cm (10 mm) in the longest diameter.
  6. Maximum one prior systemic therapy regimen.
  7. 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.
  8. Karnofsky Performance Score (KPS) ≥ 70%.
  9. More than 4 weeks from any investigational agent.
  10. Adequate haematological, liver and renal function
  11. Able and willing to swallow and retain oral medication.
  12. Female and male patients of reproductive potential must agree to use effective contraception from screening until 90 days after discontinuing study treatment.
  13. Willing and able to sign the informed consent and to comply with the protocol for the duration of the study.

Exclusion Criteria:

  1. Central Nervous System (CNS) Lymphoma or chronic immunosuppression-associated central nervous system (CNS) lymphoma.
  2. Previous allogeneic hematopoietic stem cell transplant (HSCT transplant).
  3. Previous whole brain radiotherapy (WBRT)
  4. Other concomitant anti-tumor therapy as determined by the study team.
  5. Patients unable to undergo contrast-enhanced MRI.
  6. 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.
  7. Patient taking enzyme-inducing anti-epileptic drug (EIAED) < 7 days of the first dose of PQR309.
  8. Patient is taking a drug with a risk to promote QT prolongation and Torsades de Pointes.
  9. 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.
  10. 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.
  11. Anxiety ≥ Common Terminology Criteria (CTC) of adverse events (AE) grade 3.
  12. 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.

  13. Presence of gastrointestinal disease or any other condition that could interfere significantly with the absorption of the study drug.
  14. 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.
  15. Patient has a history of invasive malignancy other than Primary Central Nervous System Lymphoma (PCNSL). Patients are eligible, if they are disease-free for at least 3 years and deemed to be at low risk for recurrence by the investigator. Patients diagnosed with cervical cancer in situ, basal cell or squamous cell carcinoma of the skin and treated within the past 3 years are eligible.
  16. Women who are pregnant or breast feeding.
  17. Women able to conceive and unwilling to practice an effective method of birth control from screening until 90 days after discontinuing study treatment (women of childbearing potential must have a negative serum pregnancy test within 7 days prior to first dose of PQR309).
  18. Fasting glucose > 7.0 mmol/L (126 mg/dL). or HbA1c > 6.4%.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: PQR309
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.
Oral PQR309, 80mg or 60mg daily or intermittent dosing
Other Names:
  • bimiralisib

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: Every 8 weeks up to 6 months
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of adverse events (AE) as related to the study medication.
Time Frame: Week 1 Day 1 to 30 days after last dose up to 12 months
Continous Dosing and Intermittent Dosing
Week 1 Day 1 to 30 days after last dose up to 12 months
Changes in puls rate
Time Frame: 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
Continous Dosing and Intermittent Dosing
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
Time Frame: 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
Continous Dosing and Intermittent Dosing
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
Time Frame: 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
Continous Dosing and Intermittent Dosing
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
Time Frame: 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
Continous Dosing and Intermittent Dosing
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 Physical examination according to Karnofsky Performance Status (KPS)
Time Frame: 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
Continous Dosing and Intermittent Dosing
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
Generalized anxiety disorder mood scale score (GAD7)
Time Frame: Treatment on Day 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
Continous Dosing and Intermittent Dosing
Treatment on Day 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
Depression Test PHQ-9
Time Frame: Treatment on 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
Continous Dosing and Intermittent Dosing
Treatment on 22, Day 43 and every subsequent 3 weeks, at the end of treatment and 30days after last dose
Changes in haematology
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15,Day 22, Day 36 and Day 43 and every subsequent 3 weeks, at the end of treatment and 30 days after last dose
Continous Dosing and Intermittent Dosing
Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15,Day 22, Day 36 and Day 43 and every subsequent 3 weeks, at the end of treatment and 30 days after last dose
Changes in Routine blood chemistry
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15,Day 22, Day 36 and Day 43 and every subsequent 3 weeks, at the end of treatment and 30 days after last dose
Continous Dosing and Intermittent Dosing
Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15,Day 22, Day 36 and Day 43 and every subsequent 3 weeks, at the end of treatment and 30 days after last dose
Changes of Insulin/Glucose/C-Peptide
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15,Day 22, Day 36 and Day 43 and every subsequent 3 weeks, at the end of treatment and 30 days after last dose
Continous Dosing and Intermittent Dosing
Week 1 Day 1 prior to treatment, Treatment on Day 8, Day15,Day 22, Day 36 and Day 43 and every subsequent 3 weeks, at the end of treatment and 30 days after last dose
Changes of haemostasis
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 22 and Day 43 and every subsequent 3 weeks, at the end of treatment
Continous Dosing and Intermittent Dosing
Week 1 Day 1 prior to treatment, Treatment on Day 22 and Day 43 and every subsequent 3 weeks, at the end of treatment
Changes of urinanalysis
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 22 and Day 43 and every subsequent 3 weeks, at the end of treatment
Continous Dosing and Intermittent Dosing
Week 1 Day 1 prior to treatment, Treatment on Day 22 and Day 43 and every subsequent 3 weeks, at the end of treatment
Changes of ECG
Time Frame: Week 1 Day 1 prior to treatment, Treatment on Day 22 and Day 43 and every subsequent 3 weeks, at the end of treatment
Continous Dosing and Intermittent Dosing
Week 1 Day 1 prior to treatment, Treatment on Day 22 and Day 43 and every subsequent 3 weeks, at the end of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: 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

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 12, 2015

Primary Completion (Actual)

January 12, 2018

Study Completion (Actual)

January 12, 2018

Study Registration Dates

First Submitted

January 7, 2016

First Submitted That Met QC Criteria

January 27, 2016

First Posted (Estimate)

February 1, 2016

Study Record Updates

Last Update Posted (Actual)

July 9, 2019

Last Update Submitted That Met QC Criteria

July 3, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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