Venetoclax and Obinutuzumab for Relapsed/Refractory Primary CNS Lymphoma

NCT04073147 | Terminated Phase 1

• 1 other identifier: ML40029
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary CNS Lymphoma

Keywords

venetoclax; obinutuzumab; pharmacokinetics

Outcome Measures

Primary Outcomes (1)

• Pharmacokinetics of venetoclax and obinutuzumab

  Serum concentration and CSF concentration (μg/ml)

  day 3, 15, and 28

Secondary Outcomes (6)

• Dose limiting toxicities

  Within the first 6 weeks

• Best lymphoma response achieved during induction

  During induction (3 months)

• Progression-free survival 1 (PFS1)

  Up to 15 months

• Overall survival

  Up to 15 months

• Progression-free survival 2 (PFS2)

  Up to 12 months

Study Arms (3)

Dosing group 1

EXPERIMENTAL

Venetoclax 600mg + Obinutuzumab 1000mg

Drug: Venetoclax; Drug: Obinutuzumab

Dosing group 2

EXPERIMENTAL

Venetoclax 800mg + Obinutuzumab 1000mg

Drug: Venetoclax; Drug: Obinutuzumab

Dosing group 3

EXPERIMENTAL

Venetoclax 1000mg + Obinutuzumab 1000mg

Drug: Venetoclax; Drug: Obinutuzumab

Interventions

Venetoclax DRUG

Venetoclax per os

Also known as: Venclyxto

Dosing group 1; Dosing group 2; Dosing group 3

Obinutuzumab DRUG

ObintuzumabIV

Also known as: Gazyvaro

Dosing group 1; Dosing group 2; Dosing group 3

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Klinikum Stuttgart: lead
• University Hospital Freiburg: collaborator

Study Sites (1)

Klinikum Stuttgart

Stuttgart, Baden-Wurttemberg, 70176, Germany

Location

MeSH Terms

Interventions

venetoclax; obinutuzumab

Study Officials

• Gerald Illerhaus, Prof

  Klinikum der Landeshauptstadt Stuttgart gKAö

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: August 26, 2019
• First Posted: August 29, 2019
• Study Start: May 12, 2020
• Primary Completion: November 25, 2021
• Study Completion: November 25, 2021
• Last Updated: January 19, 2022

Record last verified: 2022-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE
• Time Frame: after study completion and publication of results.
• Access Criteria: not decided yet

Locations

DE (1)