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Lymphoma, Large B-Cell, DiffusePhase 2NCT02987400

Combination of Obinutuzumab and Venetoclax in Relapsed or Refractory DLBCL

A Phase 2 study testing Venetoclax and Obinutuzumab in people with Lymphoma, Large B-Cell, Diffuse, run by Arbeitsgemeinschaft medikamentoese Tumortherapie at 6 sites in Austria.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to evaluate the clinical activity and tolerability of a combination of obinutuzumab plus venetoclax in patients with relapsed or refractory diffuse large B-cell lymphoma. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, Large B-Cell, Diffuse
What is being tested?
Venetoclax and Obinutuzumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
22 participants
Where
6 sitesAustria
Study dates
4 Jan 2017to 19 Oct 2021
Phase
Phase 2
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Diffuse large B-cell lymphoma (DLBCL)
  • with histologically confirmed relapse within 12 months after having achieved a PR or CR with initial R-anthracycline containing therapy, or
  • with refractoriness to initial R-anthracycline containing therapy (not achieving at least a partial response)
  • Bcl-2 protein expression detected by immunohistochemistry.
  • Adequate organ function,
  • At least one bi-dimensionally measurable lesion on CT scan defined as > 1.5 cm in its longest dimension.
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  • Confirmed availability of archival or freshly biopsied tumor tissue meeting protocol-defined-specifications prior to study enrolment.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
  • Adequate hematologic function (unless caused by underlying disease, as established by extensive bone marrow involvement or as a result of hypersplenism secondary to the involvement of the spleen by lymphoma per the investigator)

Who cannot join

  • Patient has received any other investigational treatment within 28 days before study entry.
  • Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of obinutuzumab or venetoclax.
  • DLBCL transformed from other malignancies or CD20 negative DLBCL.
  • Radiation, chemotherapy, or immunotherapy or any other anticancer therapy ≤ 4 weeks prior to Cycle 1 Day 1.
  • Ongoing corticosteroid use > 30 mg/day of prednisone or equivalent. Patients who received corticosteroid treatment with ≤ 30 mg/day of prednisone or equivalent must be documented to be on a stable dose of at least 4 weeks duration prior to randomization (Cycle 1 Day 1). Patients may have received a brief (< 7 days) course of systemic steroids (≤ 100 mg prednisone equivalent) prior to initiation of study therapy for control of lymphoma-related symptoms.
  • ECOG performance status ≥ 3.
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  • Female patients who are pregnant or breast-feeding.
  • Acute or uncontrolled chronic infections.
  • Known diagnosis of HIV
  • Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of PML.
  • Symptomatic neurologic disease compromising normal activities of daily living or requiring medications.
  • Any sensory or motor peripheral neuropathy greater than or equal to Grade 2.
  • Known history of any of the following cardiovascular conditions:
  • myocardial infarction within 2 years of study entry,
  • New York Heart Association (NYHA) Class III or IV heart failure,
  • evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities,
  • recent evidence (within 6 months before first dose of study drug) of a left-ventricular ejection fraction <50% .
  • Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have evidence of residual disease.
  • Patients with transformed lymphoma.
  • Primary CNS lymphoma.
  • Vaccination with live vaccines within 28 days prior to treatment.
  • History of other malignancy that could affect compliance with the protocol or interpretation of results (Patients with a history of curatively treated basal or squamous cell carcinoma or Stage 1 melanoma of the skin or in situ carcinoma of the cervix are eligible).
  • Patients with a malignancy that has been treated with surgery alone with curative intent will also be excluded, unless the malignancy has been in documented remission without treatment for ≥ 3 years prior to enrollment.
  • Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results or that could increase risk to the patient.
  • Significant pulmonary disease (including obstructive pulmonary disease and history of bronchospasm).
  • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) at study enrollment, or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks prior to Cycle 1 Day 1.
  • Requires the use of warfarin (because of potential drug-drug interactions that may potentially increase the exposure of warfarin).
  • Received the following agents within 7 days prior to the first dose of venetoclax:
  • CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin
  • Strong CYP3A inducers such as rifampin, carbamazepine
  • Consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or star fruit within 3 days prior to the first dose of venetoclax.
  • Clinically significant history of liver disease, including viral or other hepatitis, current alcohol abuse, or cirrhosis.
  • Presence of positive test results for Hepatitis B, Hepatitis C and CMV.
  • Recent major surgery (within 6 weeks prior to the start of Cycle 1 Day 1), other than for diagnosis.
  • Any of the following abnormal laboratory values:
  • Calculated creatinine clearance < 50 mL/min with the use of the 24-hour creatinine clearance or modified Cockcroft-Gault equation

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

Austria6 sites

  • UK Graz: Universitätsklinik für Innere Medizin; Klinische Abteilung für Hämatologie

    Graz, 8036

  • Medizinische Universität Innsbruck Univ.-Klinik für Innere Medizin V Hämatologie und Onkologie

    Innsbruck, 6020

  • Kepler Universitätsklinikum Linz, Med Campus III.,Univ.-Klinik für Hämatologie und Internistische Onkologie

    Linz, 4021

  • Universitätsklinik für Innere Med. III, PMU Salzburg

    Salzburg, 5020

  • AKH Meduni Wien Universitätsklinik für Innere Medizin I Klinische Abteilung für Hämatologie und Hämostaseologie

    Vienna, 1090

  • Klinikum Wels-Grieskirchen, Abteilung für Innere Medizin IV

    Wels, 4600

Other trials in Austria

About this study

Official title: Phase II Single-arm "Window-of-opportunity" Study of a Combination of Obinutuzumab (GA-101) and Venetoclax (ABT-199) in Relapsed or Refractory Diffuse Large B-cell Lymphoma (DLBCL)

The purpose of this study is to evaluate the clinical activity and tolerability of a combination of obinutuzumab plus venetoclax in patients with relapsed or refractory diffuse large B-cell lymphoma.

Read the detailed description

The study will have a 6 patient run-in phase to determine safety and to adjust treatment. Once the sixth patient has completed 21 days of treatment, withdrawn due to toxicity, or died, a formal review will be undertaken by the sponsor (AGMT). Enrolment will be halted until review is completed. If one (1) treatment related death is reported or three (3) or more patients experience CTC grade 4 events other than neutropenia, anemia, or thrombocytopenia, the study will be stopped for further recruitment. If the stopping criteria are not met, enrollment will be continued. A futility analysis will be conducted when the first 10 patients have been evaluated for response: If at least 2 patients had an objective response (CR or PR), the study will be continued.

The combination treatment will be repeated for up to 3 cycles. The first response assessment (including PET-CT) will be performed after the first cycle of obinutuzumab-venetoclax and patients with at least stable disease (SD) or better will be given another 2 cycles of therapy and then have assessment after a total of 3 cycles. Patients with complete or partial remission (CR, PR) after 3 cycles of therapy will either go on to transplant or receive 9 further cycles of the combination therapy (if transplant ineligible). Patients with progressive disease at any time-point or stable disease after 3 cycles will be taken off study.

Keywords
DLBCL, GA-101, ABT-199, relapsed DLBCL, refractory DLBCL, AGMT, Diffuse large B-cell lymphoma, window of opportunity
Medical subject headings
Lymphoma, Large B-Cell, Diffuse

What participants receive

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

  • VenetoclaxDrug

    Also called GA-101

    3 cycles followed by 9 cycles consolidation if not transplant eligible

  • ObinutuzumabDrug

    Also called Gazyvaro

    3 cycles followed by 9 cycles consolidation if not transplant eligible

Study groups in NCT02987400
Study groupRoleWhat they receive
TreatmentExperimentalObinutuzumab is given in a 21 day cycle intravenously starting at 1000 mg on day 1, 8 and 15 in cycle 1 and on day 1 of each following cycle Venetoclax is given orally at a dose of 800mg daily from day 1 of the first cycle.
Receives: Drug: Venetoclax; Drug: Obinutuzumab

What is being measured

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

  1. Clinical activity and tolerability

    Objective response rate (complete or partial responses; best response) defined by PET/CT scan and bone marrow examination examination after 3 cycles.

    Measured: After 3 cycles of treatment (9 weeks)

Secondary outcomes (6)

  1. Safety: Incidence of dose-limiting toxicities

    Incidence of dose-limiting toxicities of the combination treatment.

    Measured: 9 weeks induction plus maximum of 27 weeks consolidation

  2. Response duration

    Measured: From first documented response until end of follow up (max 108 weeks)

  3. Progression-free survival

    Measured: 72 weeks after last patient last visit

  4. Overall survival

    Measured: 72 weeks after last patient last visit

  5. Ability to proceed to further stem cell transplantation

    Assessed by number of eligible patients reaching transplant

    Measured: After 3 cycles of treatment (9 weeks)

  6. Genetically/biomarker defined subgroups

    Identification of genetically/biomarker defined subgroups regarding response and survival

    Measured: 72 weeks after last patient last visit

Timeline

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

  1. First posted9 Dec 2016 (estimated)
  2. Study start4 Jan 2017
  3. Primary completion19 Oct 2021
  4. Study completion19 Oct 2021

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
22 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02987400
Sponsor's protocol ID
AGMT_NHL-15B
Other IDs
2016-001760-10, 2016
Status last verified
Feb 2022
First submitted
6 Dec 2016
Last updated
16 Feb 2022
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Venetoclax and Obinutuzumab in people with Lymphoma, Large B-Cell, Diffuse, run by Arbeitsgemeinschaft medikamentoese Tumortherapie at 6 sites in Austria.

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 9 inclusion and 36 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: finished, as of the sponsor's last update on 16 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in Austria. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Clinical activity and tolerability (time frame: After 3 cycles of treatment (9 weeks)). 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 NCT02987400.

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 16 Feb 2022.

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