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Primary CNS LymphomaPhase 1VENOBI-CNSNCT04073147

Venetoclax and Obinutuzumab for Relapsed/Refractory Primary CNS Lymphoma

A Phase 1 study testing Venetoclax and Obinutuzumab in people with Primary CNS Lymphoma, run by Klinikum Stuttgart at 1 site in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Primary CNS Lymphoma
What is being tested?
Venetoclax and Obinutuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
4 participants
Where
1 siteGermany
Study dates
12 May 2020to 25 Nov 2021
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Klinikum Stuttgart

    Stuttgart, Baden-Wurttemberg, 70176

Other trials in Germany

About this study

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

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.

Read the 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.

Keywords
venetoclax, obinutuzumab, pharmacokinetics

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04073147
Study groupRoleWhat they receive
Dosing group 1ExperimentalVenetoclax 600mg + Obinutuzumab 1000mg
Receives: Drug: Venetoclax; Drug: Obinutuzumab
Dosing group 2ExperimentalVenetoclax 800mg + Obinutuzumab 1000mg
Receives: Drug: Venetoclax; Drug: Obinutuzumab
Dosing group 3ExperimentalVenetoclax 1000mg + Obinutuzumab 1000mg
Receives: Drug: Venetoclax; Drug: Obinutuzumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Pharmacokinetics of venetoclax and obinutuzumab

    Serum concentration and CSF concentration (μg/ml)

    Measured: day 3, 15, and 28

Secondary outcomes (6)

  1. Dose limiting toxicities

    Defined by CTCAE (version 5.0)

    Measured: Within the first 6 weeks

  2. Best lymphoma response achieved during induction

    According to IPCG criteria

    Measured: During induction (3 months)

  3. Progression-free survival 1 (PFS1)

    Time from the date of first dose until date of progression, relapse or death, whichever occurs first

    Measured: Up to 15 months

  4. Overall survival

    Time from the date of first dose until date of death

    Measured: Up to 15 months

  5. 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.

    Measured: Up to 12 months

  6. Mutational landscape of lymphoma

    NGS test based on FoundationOne Heme® platform

    Measured: At baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 Aug 2019
  2. Study start12 May 2020
  3. Primary completion25 Nov 2021
  4. Study completion25 Nov 2021

Why it stopped: low recruitment

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Model description
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
Masking
None (open label)
Enrolment
4 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04073147
Sponsor's protocol ID
ML40029
Acronym
VENOBI-CNS
Status last verified
Jan 2022
First submitted
26 Aug 2019
Last updated
19 Jan 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: IPD will by made available on a data depository (e.g. https://datadryad.org/) after study completion and publication of results.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Venetoclax and Obinutuzumab in people with Primary CNS Lymphoma, run by Klinikum Stuttgart at 1 site in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Jan 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: low recruitment). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Pharmacokinetics of venetoclax and obinutuzumab (time frame: day 3, 15, and 28). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04073147.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jan 2022.

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