Chemotherapy free treatment with venetoclax and obinutuzumab for relapsed /refractory primary CNS lymphoma patients (VENOBI-CNS study) – A phase IBstudy to assess the pharmacokinetics in the cerebrospinal fluid
- Conditions
- C83.3C79.3Diffuse large B-cell lymphomaSecondary malignant neoplasm of brain and cerebral meninges
- Registration Number
- DRKS00017615
- Lead Sponsor
- Klinikum der Landeshauptstadt Stuttgart
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting stopped after recruiting started
- Sex
- All
- Target Recruitment
- 5
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/progression (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 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.
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
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. 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
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.
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Pharmacokinetics of venetoclax and obinutuzumab [Time Frame: day 3, 15, and 28]
- Secondary Outcome Measures
Name Time Method 1. Dose limiting toxicities (DLTs) during escalation of dosing Groups<br>2. Best lymphoma response achieved during induction (CR, PR, SD or<br>PD)<br>3. Progression-free survival 1 (PFS1) defined as the time from first dose until progression, relapse or death, whichever occurs first.<br>4. OS; calculated from first dose until death due to any cause.<br>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. <br>6. Distribution and frequency of genetic alterations in the lymphoma cells