Status:
TERMINATED
Venetoclax and Obinutuzumab for Relapsed/Refractory Primary CNS Lymphoma
Lead Sponsor:
Klinikum Stuttgart
Collaborating Sponsors:
University Hospital Freiburg
Conditions:
Primary CNS Lymphoma
Eligibility:
All Genders
18-85 years
Phase:
PHASE1
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.
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...
Eligibility Criteria
Inclusion
- Inclusion criteria:
- Age at inclusion ≥ 18 to 80 years, in case of ECOG 0 to 1 age up to 85 years
- Eastern Cooperative Group performance status (ECOG) ≤ 3
- Evaluable lymphoma manifestation in the CNS, either contrast-enhanced lesion in the brain parenchyma or measurable meningeal lesions.
- Biopsy proven CD20 positive PCNSL at initial diagnosis or previous relapse/progression (re-biopsy at study inclusion is not mandatory for inclusion, but strongly recommended if time in remission is longer than 24 months).
- At least one prior HD-MTX containing chemotherapy application (MTX dosed at ≥ 1 g/m2 body surface area) before progression or relapse.
- Confirmed relapsed or refractory PCNSL according to the IPCG response criteria with the following definition: Evidence of disease recurrence following PR/CR or uCR or no radiological response (SD or PD) as per the IPCG criteria to prior chemotherapy regimen(s), at least one of them containing high-dose methotrexate.
- Absolute neutrophil count (ANC) of at least 1'500/μl
- Platelet count of at least 50'000/μl
- 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)
- Written informed consent
- Recovery from toxicity from previous anti-lymphoma treatment to ≤ grade 2
- Exclusion criteria:
- Known allergy to venetoclax or other components of the formulation
- Known allergy to obinutuzumab or other components of the formulation
- Primary ocular lymphomas without brain parenchymal involvement
- Lymphoma relapse outside the CNS; extra CNS relapse needs to be ruled out by body CT scans (neck till pelvis) or PET-CT scans.
- Contraindications for lumbar puncture at the discretion of the clinical investigator
- Prior exposure to obinutuzumab or venetoclax
- Other additional anti-lymphoma treatment, e.g. chemotherapy or radiotherapy
- Active hepatitis B or C
- HIV seropositivity
- Chronic use of immunosuppressive drugs, e.g. steroids for systemic autoimmune disease
- Active infections requiring treatment
- Other active malignancies (except non-melanoma skin cancer). Prior malignancies without evidence of disease for at least 5 years are allowed
- Patient is pregnant or breastfeeding, or expecting to conceive or father children within one year of finishing venetoclax and 18 months for obinutuzumab.
- Prior allogeneic haematopoietic stem cell or solid organ transplantation
- Therapeutic intervention in setting of other former interventional clinical trial within 30 days before the first IMP administration in VENOBI study; simultaneous participation in registry and diagnostic studies or follow up of an interventional trial is allowed
- Patient without legal capacity who is unable to understand the nature, significance and consequences of the trial
- Known or persistent abuse of medication, drugs or alcohol
- Person who is in a relationship of dependence/employment with the sponsor or the investigator
- Administration of moderate or strong CYP3A inhibitors or inducers within 1 week of initiation of venetoclax dosing.
Exclusion
Key Trial Info
Start Date :
May 12 2020
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
November 25 2021
Estimated Enrollment :
4 Patients enrolled
Trial Details
Trial ID
NCT04073147
Start Date
May 12 2020
End Date
November 25 2021
Last Update
January 19 2022
Active Locations (1)
Enter a location and click search to find clinical trials sorted by distance.
1
Klinikum Stuttgart
Stuttgart, Baden-Wurttemberg, Germany, 70176