Venetoclax and Obinutuzumab for Relapsed/Refractory Primary CNS Lymphoma (VENOBI-CNS)

January 18, 2022 updated by: Klinikum Stuttgart

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
4

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
    • Baden-Württemberg
      • Stuttgart, Baden-Württemberg, Germany, 70176
        • Klinikum Stuttgart

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Dosing group 1
Venetoclax 600mg + Obinutuzumab 1000mg
Drug: Venetoclax
Venetoclax per os
Other Names:
  • Venclyxto
Drug: Obinutuzumab
ObintuzumabIV
Other Names:
  • Gazyvaro
Experimental: Dosing group 2
Venetoclax 800mg + Obinutuzumab 1000mg
Drug: Venetoclax
Venetoclax per os
Other Names:
  • Venclyxto
Drug: Obinutuzumab
ObintuzumabIV
Other Names:
  • Gazyvaro
Experimental: Dosing group 3
Venetoclax 1000mg + Obinutuzumab 1000mg
Drug: Venetoclax
Venetoclax per os
Other Names:
  • Venclyxto
Drug: Obinutuzumab
ObintuzumabIV
Other Names:
  • Gazyvaro

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Pharmacokinetics of venetoclax and obinutuzumab
Time Frame: day 3, 15, and 28
Serum concentration and CSF concentration (μg/ml)
day 3, 15, and 28

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Dose limiting toxicities
Time Frame: Within the first 6 weeks
Defined by CTCAE (version 5.0)
Within the first 6 weeks
Best lymphoma response achieved during induction
Time Frame: During induction (3 months)
According to IPCG criteria
During induction (3 months)
Progression-free survival 1 (PFS1)
Time Frame: Up to 15 months
Time from the date of first dose until date of progression, relapse or death, whichever occurs first
Up to 15 months
Overall survival
Time Frame: Up to 15 months
Time from the date of first dose until date of death
Up to 15 months
Progression-free survival 2 (PFS2)
Time Frame: Up to 12 months
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
Mutational landscape of lymphoma
Time Frame: At baseline
NGS test based on FoundationOne Heme® platform
At baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Klinikum Stuttgart

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University Hospital Freiburg

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Gerald Illerhaus, Prof, Klinikum der Landeshauptstadt Stuttgart gKAö

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 12, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 25, 2021

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 25, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 26, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 29, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 19, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 18, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • ML40029

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

IPD will by made available on a data depository (e.g. https://datadryad.org/) after study completion and publication of results.

IPD Sharing Time Frame

after study completion and publication of results.

IPD Sharing Access Criteria

not decided yet

IPD Sharing Supporting Information Type

  • Analytic Code

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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