NHLPhase 2HO151DLBCLNCT03463057
The Feasibility and Clinical Efficacy of Atezolizumab Consolidation Treatment in High Risk (IPI > 2) DLBCL
A Phase 2 study testing Atezolizumab in people with NHL and DLBCL, run by Stichting Hemato-Oncologie voor Volwassenen Nederland at 32 sites in 2 countries.
Trial summary
The prognosis of Diffuse Large B cell Lymphoma (DLBCL) patients with an early relapse is dismal. Atezolizumab has shown promising activity in relapsed DLBCL patients. Toxicity data on atezolizumab are available for > 6000 patients and is manageable. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- What is being tested?
- Atezolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 109 participants
- Where
- 32 sitesin 2 countries
- Study dates
- 30 Aug 2018to Jan 2027
- Phase
- Phase 2
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 (inclusive) years
- Patients with a confirmed histologic diagnosis of diffuse large B-cell lymphoma (DLBCL-NOS) based upon a representative histology specimen according to the World Health Association (WHO) classification, revision 2016
- Ann Arbor stages II-IV
- WHO performance status 0 - 1
- International Prognostic Index (IPI) ≥ 3 at diagnosis
- Complete metabolic remission (Deauville 1-3) after 6-8 cycles of R-CHOP according to the Lugano criteria
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- Of note:
- Rituximab may have been administered either intravenously or subcutaneously. A rituximab biosimilar may have been used when it is approved for the indication of DLBCL.
- Patients should have received at least 6 cycles R-CHOP. Dose reductions for vincristine are allowed during R-CHOP. Dose reductions because of bone marrow toxicity are allowed but cannot exceed >15% of cumulative dose of doxorubicin and cyclophosphamide.
- Central nervous system prophylaxis (MTX) by intrathecal therapy or IV is allowed.
- Fludeoxyglucose Positron Emission Tomography (18F-FDG-PET) scan should have been made 4-8 weeks after last induction cycle
- Histologically confirmed false positive EoT PET-scans are eligible.
- Negative pregnancy test at study entry
- Patient is willing and able use adequate contraception during and until 5 months after the last protocol treatment.
- Patient is capable of giving a written informed consent
Who cannot join
- Diagnosis
- All histopathological diagnoses other than DLBCL-NOS according to the WHO classification, revision 2016, including:
- High-grade B-cell lymphoma with a double/triple translocation with MYC, BCL2 and/or BCL6. Please note that patients with an isolated MYC translocation or an isolated BCL2 translocation or an isolated BCL-6 translocation are eligible (single hit translocation).
- Testicular large B-cell lymphoma
- Primary mediastinal B cell lymphoma
- Transformed indolent lymphoma
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- Post-transplant lymphoproliferative disorder
- Organ dysfunction
- Clinical signs of severe pulmonary dysfunction
- Clinical signs of heart failure (New York Heart Association (NYHA) classification II-IV)
- Symptomatic coronary artery disease or cardiac arrhythmias not well controlled with medication.
- Myocardial infarction during the last 6 months
- Significant renal dysfunction (serum creatinine ≥ 150 umol/l or clearance ≤ 30ml/min
- Creatinine clearance (CrCl) may be calculated by Cockcroft -Gault formula:
- CrCl = (140 - age [in years]) x weight [kg] (x 0.85 for females)/(0.815 x serum creatinine [μmol/L])
- Inadequate hematological function: hemoglobin < 5.5 mmol/L Absolute Neutrophil Count (ANC) < 1.0x10↑9/L or platelets < 75x10↑9 /L
- Signs or known history of bleeding disorder.
- Significant hepatic dysfunction (total bilirubin ≥ 1.5x upper limit of normal (ULN) or transaminases ≥ 2.5 x ULN), unless related to Gilberts syndrome.
- Clinical signs of severe cerebral dysfunction
- Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs
- Major surgery within the last 4 weeks
- Known or suspected infection • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks of the start of Cycle 1. Suspected active or latent tuberculosis needs to be confirmed by positive interferon gamma (IFN-γ) release assay
- Patients known to be Human Immuno-deficiency Virus (HIV)-positive
- Active chronic hepatitis B or C infection
- Administration of a live, attenuated vaccine within 4 weeks before date of registration or anticipation that such a live attenuated vaccine will be required during the study and for a period of 5 months after discontinuation of atezolizumab
- Auto-immune • Any active or history of documented autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
- The following exceptions are allowed: Patients with autoimmune-related hypothyroidism or type 1 diabetes mellitus who are on stable treatment.
- History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis per chest computer tomography (CT) scan at screening.
- Patients with uncontrolled asthma or allergy, requiring systemic steroid treatment
- Regular treatment with corticosteroids within the 4 weeks prior to date of registration, unless administered for indications other than NHL at a dose equivalent to < 30 mg/day prednisone/prednisolone
- General
- Serious underlying medical conditions, which could impair the ability of the patient to participate in the trial (e.g. ongoing infection, uncontrolled diabetes mellitus, gastric ulcers, active autoimmune disease)
- Current participation in another clinical trial interfering with this trial
- History of active cancer during the past 5 years, except basal cell carcinoma of the skin, stage 0 cervical carcinoma or carcinoma in situ (for which no systemic treatment was indicated)
- Life expectancy < 6 months
- Any psychological, familial, sociological and geographical condition potentially hampering compliance with the study protocol and follow-up schedule
- Prior treatment
- Prior treatment with Atezolizumab, or anti-programmed cell death protein-1 (anti PD-1) or PDL-1 antibodies.
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA4 therapeutic antibodies.
- Treatment with systemic immunostimulatory agents (including but not limited to IFN, interleukin [IL]-2) within 6 weeks or 5 half-lives of the drug, whichever is shorter, prior to Cycle 1, Day 1.
- Treatment with systemic immunosuppressive medications, including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor (anti-TNF) agents within 2 weeks prior to date of registration; inhaled corticosteroids and mineralocorticoids are allowed.
Trial locations and contacts
32 sites in 2 countries.
32 sites in 2 countries
Netherlands27 sites
NL-Den Bosch-JBZ
's-Hertogenbosch
NL-Amersfoort-MEANDERMC
Amersfoort
NL-Amsterdam-OLVG
Amsterdam
NL-Amsterdam-VUMC
Amsterdam
NL-Apeldoorn-GELREAPELDOORN
Apeldoorn
NL-Breda-AMPHIA
Breda
NL-Delft-RDGG
Delft
NL-Dordrecht-ASZ
Dordrecht
NL-Ede-ZGV
Ede
NL-Eindhoven-CATHARINA
Eindhoven
NL-Eindhoven-MAXIMAMC
Eindhoven
NL-Enschede-MST
Enschede
NL-Groningen-UMCG
Groningen
NL-Hilversum-TERGOOI
Hilversum
NL-Hoofddorp-SPAARNEGASTHUIS
Hoofddorp
NL-Leeuwarden-MCL
Leeuwarden
NL-Leiden-LUMC
Leiden
NL-Maastricht-MUMC
Maastricht
NL-Nieuwegein-ANTONIUS
Nieuwegein
NL-Nijmegen-CWZ
Nijmegen
NL-Rotterdam-ERASMUSMC
Rotterdam
NL-Rotterdam-MAASSTADZIEKENHUIS
Rotterdam
NL-Sittard-Geleen-ZUYDERLAND
Sittard
NL-Den Haag-HAGA
The Hague
NL-Tilburg-ETZ
Tilburg
NL-Utrecht-UMCUTRECHT
Utrecht
NL-Zwolle-ISALA
Zwolle
Belgium5 sites
BE-Antwerpen Edegem-UZA
Antwerp
BE-Antwerpen-ZNASTUIVENBERG
Antwerp
BE-Brugge-AZBRUGGE
Bruges
BE-Leuven-UZLEUVEN
Leuven
BE-Roeselare-AZDELTA
Roeselare
About this study
Official title: A Phase II Study Evaluating the Feasibility and Clinical Efficacy of Atezolizumab Consolidation Treatment in High Risk Diffuse Large B-cell Lymphoma
The prognosis of Diffuse Large B cell Lymphoma (DLBCL) patients with an early relapse is dismal. Atezolizumab has shown promising activity in relapsed DLBCL patients. Toxicity data on atezolizumab are available for > 6000 patients and is manageable. The assumption of this study is that atezolizumab consolidation will result in higher disease free survival by eradicating minimal residual disease In melanoma and lung cancer consolidation immunotherapy after chemoradiotherapy has shown an increase in survival.
Read the detailed description
In high risk diffuse large B-cell lymphoma (DLBCL), International Prognostic Index (IPI)-score ≥ 3 21% of patients will relapse within 2-years after completion of R-CHOP induction treatment despite achieving a complete remission. Patient relapsing within a year after R-CHOP treatment have a very poor prognosis, even after second line chemotherapy, with only 15% of patients achieving a long remission. Therefore, additional therapy in first line treatment is required for these patients. The immune checkpoint inhibitor atezolizumab is a monoclonal antibody directed against the program death ligand 1 (PDL1). The PD1 and PDL1 inhibitors have shown excellent results in relapsed Hodgkin lymphoma and promising results in relapsed B-cell non Hodgkin lymphoma. Given the acceptable toxicity profile of atezolizumab, this study examines the efficacy and toxicity of atezolizumab as consolidation treatment after R-CHOP induction in DLBCL patients at high risk of relapse.
- Being tested
- Atezolizumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabDrug
Also called Tecentriq, L01XC
Intervention Atezolizumab starts after 6 - 8 R-CHOP induction cycles (Rituximab, Cyclophosphamide, Hydroxo-doxorubicin, Vincristine and Prednisone (R-CHOP)); 18 cycles Atezolizumab followed by 12 months of observation
| Study group | Role | What they receive |
|---|---|---|
| Atezolizumab | Other | 18 cycles atezolizumab followed by 12 months of observation Receives: Drug: Atezolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease free survival (DFS) measured from the date of registration to relapse or death from any cause whichever comes first.
To evaluate the 2-year DFS for patients in complete metabolic remission after R-CHOP induction
Measured: 2 year after inclusion last patient
Secondary outcomes (5)
(Severe) Adverse Events and the relation of adverse events in time to the recovery of the T-cell repertoire.
To evaluate toxicity and assess the relation of adverse events in time to recovery of the T-cell repertoire.
Measured: 2 years after inclusion last patient
Overall survival (OS), calculated from registration until death from any cause. Patients still alive or lost to follow up are censored at the last date known to be alive.
To evaluate the 2-year OS.
Measured: 2 years after inclusion last patient
The relationship between MRD status at the end-of-induction and end-of-consolidation therapy.
To evaluate MRD status at the end of induction therapy, at various time points during consolidation treatment and at the end of consolidation.
Measured: 2 years after inclusion last patient
The relation between MRD conversion and 2-years DFS and OS.
To evaluate if there is a relation between MRD conversion and 2-years DFS and OS.
Measured: 2 years after inclusion last patient
The relation between the T-cell and NK cell repertoire and adverse events.
To evaluate the recovery of the T-cell and NK cell repertoire after induction therapy and at various time points during consolidation treatment in relation to toxicity and efficacy.
Measured: 2 years after inclusion last patient
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2018
- Study start30 Aug 2018
- Primary completion18 Jan 2024
- Study completionJan 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NHLStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 109 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stichting Hemato-Oncologie voor Volwassenen Nederland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- M. Nijland, PhD/MD, Principal investigator, NL-Groningen-UMCG
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03463057
- Sponsor's protocol ID
- HO151
- Other IDs
- 2017-002605-35, 2017
- Acronym
- HO151DLBCL
- Status last verified
- Sep 2026
- First submitted
- 23 Feb 2018
- Last updated
- 23 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Nijland M, Issa DE, Bult JAA, Deeren D, Velders GA, Nijziel MR, Sandberg Y, Vergote V, Oosterveld M, Fijnheer R, Brouwer RE, Boersma RS, Wu K, Nieuwenhuizen L, Vermaat JSP, van Kampen RJW, Terpstra WE, Snauwaert S, van der Poel MW, de Jongh E, Durian MF, Strobbe L, Beeker A, Gadisseur A, van Rijn RS, Visser O, Doorduijn JK, Snijders TJF, Silbermann MH, de Jong D, Chamuleau M, Mous R, Jalving H, Visser-Wisselaar H, Jansen van de Bergh S, Zwezerijnen GJC, Bremer E, Brink M, Diepstra A, Chitu DA, Koene HR, Zijlstra JM. Atezolizumab consolidation in patients with high-risk diffuse large B-cell lymphoma in complete remission after R-CHOP. Blood Adv. 2025 Jul 22;9(14):3530-3539. doi: 10.1182/bloodadvances.2024015226.
PubMed 40249860