Venetoclax and Obinutuzumab for Relapsed/Refractory Primary CNS Lymphoma

Primary CNS Lymphoma Clinical Trial

— VENOBI-CNS  

Official title:

Chemotherapy Free Treatment With Venetoclax and Obinutuzumab for Relapsed / Refractory Primary CNS Lymphoma Patients (VENOBI-CNS Study) - A Phase IB Study to Assess the Pharmacokinetics in the Cerebrospinal Fluid

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04073147
• Other study ID #: ML40029
• Status: Terminated
• Phase: Phase 1
• Start date: May 12, 2020
• Est. completion date: November 25, 2021

Study information

• Verified date: January 2022
• Source: Klinikum Stuttgart
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: November 25, 2021
• Est. primary completion date: November 25, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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/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

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. 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.

Related Conditions & MeSH terms

• Lymphoma
• Primary CNS Lymphoma

Intervention

Drug:
• Venetoclax
Venetoclax per os
• Obinutuzumab
ObintuzumabIV

Locations

Country	Name	City	State
Germany	Klinikum Stuttgart	Stuttgart	Baden-Württemberg

Sponsors (2)

Lead Sponsor	Collaborator
Klinikum Stuttgart	University Hospital Freiburg

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pharmacokinetics of venetoclax and obinutuzumab	Serum concentration and CSF concentration (µg/ml)	day 3, 15, and 28
Secondary	Dose limiting toxicities	Defined by CTCAE (version 5.0)	Within the first 6 weeks
Secondary	Best lymphoma response achieved during induction	According to IPCG criteria	During induction (3 months)
Secondary	Progression-free survival 1 (PFS1)	Time from the date of first dose until date of progression, relapse or death, whichever occurs first	Up to 15 months
Secondary	Overall survival	Time from the date of first dose until date of death	Up to 15 months
Secondary	Progression-free survival 2 (PFS2)	Time from the start of maintenance venetoclax treatment at week 12 until date of progression, relapse or death, whichever occurs first.	Up to 12 months
Secondary	Mutational landscape of lymphoma	NGS test based on FoundationOne Heme® platform	At baseline