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Venetoclax and Obinutuzumab for Relapsed Primary CNS Lymphoma (VENOBI-CNS)

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ClinicalTrials.gov Identifier: NCT04073147
Recruitment Status : Not yet recruiting
First Posted : August 29, 2019
Last Update Posted : August 29, 2019
Sponsor:
Collaborator:
University Hospital Freiburg
Information provided by (Responsible Party):
Klinikum Stuttgart

Brief Summary:
This is a phase IB study investigating the pharmacokinetics of the combination venetoclax and obinutuzumab in the cerebrospinal fluid of patient with relapsed primary CNS lymphoma.

Condition or disease Intervention/treatment Phase
Primary CNS Lymphoma Drug: Venetoclax Drug: Obinutuzumab Phase 1

Detailed Description:
This is a phase IB study investigating the pharmacokinetics of the combination venetoclax and obinutuzumab in the cerebrospinal fluid of patient with relapsed primary CNS lymphoma. Three dosing groups of venetoclax (600mg, 800mg, and 1000mg) are planned; dosing of obinutuzumab will be 1000mg for each dosing group. 15 patients are planned being included from two centers in Germany.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Three sequential dosing groups. Starting with dosing group 1 (5 patients), followed by dosing group 2 (5 patients) if no dose limiting toxicities occur during dosing group 1, and finally followed by dosing group 3 (5 patients) if no dose limiting toxicities occur in dosing group 2
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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
Estimated Study Start Date : November 2019
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : December 2023


Arm Intervention/treatment
Experimental: Dosing group 1
Venetoclax 600mg + Obinutuzumab 1000mg
Drug: Venetoclax
Venetoclax per os
Other Name: Venclyxto

Drug: Obinutuzumab
ObintuzumabIV
Other Name: Gazyvaro

Experimental: Dosing group 2
Venetoclax 800mg + Obinutuzumab 1000mg
Drug: Venetoclax
Venetoclax per os
Other Name: Venclyxto

Drug: Obinutuzumab
ObintuzumabIV
Other Name: Gazyvaro

Experimental: Dosing group 3
Venetoclax 1000mg + Obinutuzumab 1000mg
Drug: Venetoclax
Venetoclax per os
Other Name: Venclyxto

Drug: Obinutuzumab
ObintuzumabIV
Other Name: Gazyvaro




Primary Outcome Measures :
  1. Pharmacokinetics of venetoclax and obinutuzumab [ Time Frame: day 3, 15, and 28 ]
    Serum concentration and CSF concentration (μg/ml)


Secondary Outcome Measures :
  1. Dose limiting toxicities [ Time Frame: Within the first 6 weeks ]
    Defined by CTCAE (version 5.0)

  2. Best lymphoma response achieved during induction [ Time Frame: During induction (3 months) ]
    According to IPCG criteria

  3. Progression-free survival 1 (PFS1) [ Time Frame: Up to 15 months ]
    Time from the date of first dose until date of progression, relapse or death, whichever occurs first

  4. Overall survival [ Time Frame: Up to 15 months ]
    Time from the date of first dose until date of death

  5. Progression-free survival 2 (PFS2) [ Time Frame: Up to 12 months ]
    Time from the start of maintenance venetoclax treatment at week 12 until date of progression, relapse or death, whichever occurs first.

  6. Mutational landscape of lymphoma [ Time Frame: At baseline ]
    NGS test based on FoundationOne Heme® platform



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age at inclusion ≥18 to 80 years, in case of ECOG 0 to 1 age up to 85years
  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

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. Chronicuseofimmunosuppressivedrugs,e.g.steroidsforsystemic 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. Personwhoisinarelationshipofdependence/employmentwiththesponsor or the investigator
  19. Administration of moderate or strong CYP3A inhibitors or inducers within 1 week of initiation of venetoclax dosing.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04073147


Contacts
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Contact: Gerald Illerhaus, Prof +4971127830400 g.illerhaus@klinikum-stuttgart.de
Contact: Elisabeth Schorb, MD +4976127035360 elisabeth.schorb@uniklinik-freiburg.de

Locations
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Germany
Klinikum Stuttgart
Stuttgart, Baden-Württemberg, Germany, 70176
Sponsors and Collaborators
Klinikum Stuttgart
University Hospital Freiburg
Investigators
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Study Chair: Gerald Illerhaus, Prof Klinikum der Landeshauptstadt Stuttgart gKAö

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Responsible Party: Klinikum Stuttgart
ClinicalTrials.gov Identifier: NCT04073147     History of Changes
Other Study ID Numbers: ML40029
First Posted: August 29, 2019    Key Record Dates
Last Update Posted: August 29, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD will by made available on a data depository (e.g. https://datadryad.org/) after study completion and publication of results.
Supporting Materials: Analytic Code
Time Frame: after study completion and publication of results.
Access Criteria: not decided yet

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Klinikum Stuttgart:
venetoclax
obinutuzumab
pharmacokinetics
Additional relevant MeSH terms:
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Venetoclax
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Obinutuzumab
Antineoplastic Agents
Antineoplastic Agents, Immunological