Venetoclax and Obinutuzumab for Relapsed/Refractory Primary CNS Lymphoma

NCT ID: NCT04073147

Last Updated: 2022-01-19

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-12
• Study Completion Date: 2021-11-25

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 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.

Conditions

Primary CNS Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Dosing group 1

Venetoclax 600mg + Obinutuzumab 1000mg

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Venetoclax per os

Obinutuzumab

Intervention Type: DRUG

ObintuzumabIV

Dosing group 2

Venetoclax 800mg + Obinutuzumab 1000mg

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Venetoclax per os

Obinutuzumab

Intervention Type: DRUG

ObintuzumabIV

Dosing group 3

Venetoclax 1000mg + Obinutuzumab 1000mg

Group Type: EXPERIMENTAL

Venetoclax

Intervention Type: DRUG

Venetoclax per os

Obinutuzumab

Intervention Type: DRUG

ObintuzumabIV

Interventions

Venetoclax

Venetoclax per os

Intervention Type: DRUG

Obinutuzumab

ObintuzumabIV

Intervention Type: DRUG

Other Intervention Names

Venclyxto; Gazyvaro

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Freiburg

OTHER

Sponsor Role: collaborator

Klinikum Stuttgart

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gerald Illerhaus, Prof

Role: STUDY_CHAIR

Klinikum der Landeshauptstadt Stuttgart gKAö

Locations

Klinikum Stuttgart

Stuttgart, Baden-Wurttemberg, Germany

Countries

Germany

Other Identifiers

ML40029

Identifier Type: -

Identifier Source: org_study_id