Trial document




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  DRKS00017615

Trial Description

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Title

Chemotherapy free treatment with venetoclax and obinutuzumab for relapsed primary CNS lymphoma patients (VENOBI-CNS study) – A phase IB study to assess the pharmacokinetics in the cerebrospinal fluid

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Trial Acronym

VENOBI-CNS

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URL of the Trial

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Brief Summary in Lay Language

Chemotherapy-free treatment with Venetoclax und Obinutuzumab for relapsed primary CNS lymphoma patients - a IB study to assess how a drug affects the cerebrospinal fluid with reference to absorption, distribution, metabolism and elimination.

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Brief Summary in Scientific Language

There is no standard treatment for relapsed or refractory PCNSL and strategies highly depend on previous treatments and clinical performance status.
This single arm multicentre phase IB dose-escalation trial aims to investigate a chemotherapy free treatment of venetoclax in combination with fixed-dose obinutuzumab in relapsed immunocompetent PCNSL patients.

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Do you plan to share individual participant data with other researchers?

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Description IPD sharing plan:

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Organizational Data

  •   DRKS00017615
  •   2020/01/22
  •   2019/08/26
  •   yes
  •   Approved
  •   AM-2019-028-ff, Ethik-Kommission bei der Landesärztekammer Baden-Württemberg
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Secondary IDs

  •   2017-003690-33 
  •   NCT04073147  (ClinicalTrials.gov)
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Health Condition or Problem studied

  •   C83.3 -  Diffuse large B-cell lymphoma
  •   C79.3 -  Secondary malignant neoplasm of brain and cerebral meninges
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Interventions/Observational Groups

  •   All patients are planned to receive six cycles of induction treatment (combination of obinutuzumab and venetoclax, 18 weeks [six 3 weekly cycles]) and if at least stable disease without clinical deterioration has been achieved, patients will go on to maintenance treatment for 12 months with venetoclax.

    During the combination induction phase, obinutuzumab at 1000mg will be given for 6 cycles (day 1, 8 & 15 [first cycle] and on day 1 in cycles 2 till 6) together with daily venetoclax (600mg [N=5], 800mg [N=5] or 1000mg [N=5]).
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I
  •   Yes
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Primary Outcome

Pharmacokinetics of venetoclax and obinutuzumab [Time Frame: day 3, 15, and 28]

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Secondary Outcome

1. Dose limiting toxicities (DLTs) during escalation of dosing Groups
2. Best lymphoma response achieved during induction (CR, PR, SD or
PD)
3. Progression-free survival 1 (PFS1) defined as the time from first dose until progression, relapse or death, whichever occurs first.
4. OS; calculated from first dose until death due to any cause.
5. Progression-free survival 2 (PFS2), defined as the time from start of maintenance Treatment until date of progression, relapse or death, whichever occurs first.
6. Distribution and frequency of genetic alterations in the lymphoma cells

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  • Medical Center 
  • University Medical Center 
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Recruitment

  •   Planned
  •   2020/02/09
  •   15
  •   Multicenter trial
  •   National
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   80   Years
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Additional Inclusion Criteria

1. Age at inclusion ≥ 18 to 80 years, in case of ECOG 0 to 1 age up to 85 years
2. Eastern Cooperative Group performance status (ECOG) ≤ 3
3. Evaluable lymphoma manifestation in the CNS, either contrast-enhanced lesion in the brain parenchyma or measurable meningeal lesions.
4. Biopsy proven CD20 positive PCNSL at initial diagnosis or previous relapse (re-biopsy at study inclusion is not mandatory for inclusion, but strongly recommended if time in remission is longer than 24 months).
5. At least one prior HD-MTX containing chemotherapy application (MTX dosed at ≥ 1 g/m2 body surface area) before progression or relapse.
6. Confirmed lymphoma relapse according to the IPCG response criteria.
7. Absolute neutrophil count (ANC) of at least 1’500/μl
8. Platelet count of at least 50’000/μl
9. Adequate liver (alanine aminotransferase [ALAT] and AST ≤ 3.0 x upper limit of normal [ULN] and total bilirubin ≤ 1.5 x ULN) and kidney function (estimated ≥ 30ml/min creatinine clearance according to Cockgroft-Gault formula)
10. Written informed consent
11. Recovery from toxicity from previous anti-lymphoma treatment to ≤ grade 2

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Exclusion Criteria

1. Known allergy to venetoclax or other components of the formulation
2. Known allergy to obinutuzumab or other components of the formulation
3. Primary ocular lymphomas without brain parenchymal involvement
4. Lymphoma relapse outside the CNS; extra CNS relapse needs to be ruled out by body CT scans (neck till pelvis) or PET-CT scans.
5. Contraindications for lumbar puncture at the discretion of the clinical investigator
6. Prior exposure to obinutuzumab or venetoclax
7. Other additional anti-lymphoma treatment, e.g. chemotherapy or radiotherapy
8. Active hepatitis B or C
9. HIV seropositivity
10. Chronic use of immunosuppressive drugs, e.g. steroids for systemic autoimmune disease
11. Active infections requiring treatment
12. Other active malignancies (except non-melanoma skin cancer). Prior malignancies without evidence of disease for at least 5 years are allowed
13. Patient is pregnant or breastfeeding, or expecting to conceive or father children within one year of finishing venetoclax and 18 months for obinutuzumab.
14. Prior allogeneic haematopoietic stem cell or solid organ transplantation
15. Participation in any other interventional clinical trial within the last 30 days before the start of this trial; simultaneous participation in registry and diagnostic studies is allowed
16. Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial
17. Known or persistent abuse of medication, drugs or alcohol
18. Person who is in a relationship of dependence/employment with the sponsor or the investigator
19. Administration of moderate or strong CYP3A inhibitors or inducers within 1 week of initiation of venetoclax dosing.

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Addresses

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    • Klinikum der Landeshauptstadt Stuttgart
    • Kriegsbergstr. 60
    • 70174  Stuttgart
    • Germany
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    • Klinikum Stuttgart
    • Mr.  Professor Dr  Gerald  Illerhaus 
    • Kriegsbergstr. 60
    • 70174  Stuttgart
    • Germany
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    • Klinikum Stuttgart
    • Mr.  Professor Dr  Gerald  Illerhaus 
    • Kriegsbergstr. 60
    • 70174  Stuttgart
    • Germany
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Sources of Monetary or Material Support

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    • Roche Pharma AG
    • 79639  Grenzach-Whylen
    • Germany
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Status

  •   Recruiting planned
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Trial Publications, Results and other Documents

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