Clinical trial NCT04332822: A Randomized, Multicenter, Phase III Trial Comparing Treatment With R-mini-CHOP With R-mini-CHP + Polatuzumab Vedotin in Patients With Diffuse Large Cell B Cell Lymphoma
Official title: R-MINI-CHOP Versus R-MINI-CHP in Combination With Polatuzumab-vedotin, as Primary Treatment for Patients With Diffuse Large B-cell Lymphoma, ≥80 Years, or Frail ≥75 Years - an Open Label Randomized Nordic Lymphoma Group Phase III Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: DLBCL
Diffuse Large B Cell Lymphoma
Keywords: DLBCL
Diffuse Large B Cell Lymphoma
Lead sponsor: Nordic Lymphoma Group
Sponsor class: NETWORK
Collaborators: name: Roche Pharma AG
First posted: 2020-04-03
Enrollment: 300
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a phase III, randomized, open-label, multicenter trial, conducted in Sweden, Norway, Finland, Denmark, Italy, Australia and New Zealand, in elderly patients with untreated diffuse large B-cell lymphoma. Elderly is defined as either ≥80 years of age, or ≥75 years and frail, according to a simplified Comprehensive Geriatric Assessment. Patients will be randomized 1:1 to either the standard treatment for this population, R-miniCHOP, or an experimental regimen, R-pola-miniCHP, where vincristine is substituted by an immunoconjugate, polatuzumab vedotin. The duration of the screening period is up to 4 weeks. The duration of active treatment is 18 weeks in both arms, and patients will be followed up to 36 months after end of treatment. Start of enrollment is planned in Q1 2020, and the last visit of the last patient included (end of trial) is estimated in Q1 2027.


Eligibility criteria: Inclusion Criteria:

* Age ≥80 years or frail ≥75 years, according to simplified comprehensive geriatric assessment
* Histologically confirmed lymphoma belonging to one of the following subtypes:

  1. diffuse large B-cell lymphoma, including transformation from an indolent lymphoma
  2. follicular lymphoma grade 3B
  3. T-cell/histiocyte-rich LBCL
  4. primary cutaneous DLBCL, leg type
  5. EBV-positive DLBCL, NOS
  6. primary mediastinal LBCL
  7. high grade B-cell lymphoma with MYC/BCL2 rearrangement
* Stage II-IV disease
* At least 1 measurable site of disease (\>1.5 cm long axis)
* No previous treatment for lymphoma
* WHO performance status 0 - 3 (Grade 3 if related to DLBCL)
* Written informed consent

Exclusion Criteria:

* Severe cardiac disease: NYHA grade 3-4
* CNS involvement at diagnosis
* Uncontrolled serious infection
* Impaired liver (transaminases \> 3x normal upper limit or bilirubin \> 1.5 x normal upper limit, unless due to Gilbert´s syndrome) , renal (GFR\<30ml/min) or other organ function not caused by lymphoma, which will interfere with the treatment.
* Absolute neutrophil count (ANC) \<1000 cells/µL or platelets \<100,000 cells/µL, unless due to lymphoma
* Any other prior malignancy than non-melanoma skin cancer or stage 0 (in situ) cervical carcinoma, unless treated with curative intent, and without relapse since 2 years, or low grade prostate cancer, not in need of treatment
* Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study
* Known hypersensitivity to rituximab, polatuzumab vedotin, cyclophosphamide, vincristine or doxorubicin, or HACA against rituximab
* Peripheral neuropathy grade ≥ 2

Primary outcomes:
measure: Progression-free survival (PFS).
timeFrame: 2 years.
Secondary outcomes:
Other outcomes:
Locations:
city: Albury
country: Australia
facility: Border Medical Oncology Research Unit
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
city: Coffs Harbour
country: Australia
facility: Coffs Harbour
city: Concord
country: Australia
facility: Concord Repatriation General Hospital
city: Cudgen
country: Australia
facility: Tweed Valley Hospital
city: Garran
country: Australia
facility: The Canberra Hospital
city: Hobart
country: Australia
facility: Royal Hobart Hospital
city: Liverpool
country: Australia
facility: Liverpool
city: Melbourne
country: Australia
facility: Bendigo
city: Melbourne
country: Australia
facility: Northern Health
city: Melbourne
country: Australia
facility: St Vincent's Hospital Melbourne
city: Melbourne
country: Australia
facility: Western Health
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
city: Orange
country: Australia
facility: Orange Health
city: Perth
country: Australia
facility: Royal Perth Hospital
city: Port Macquarie
country: Australia
facility: Port Macquarie
city: Randwick
country: Australia
facility: Prince of Wales Hospital
city: St Leonards
country: Australia
facility: Royal North Shore Hospital
city: Sunshine Coast
country: Australia
facility: Sunshine Coast University Hospital
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
city: Westmead
country: Australia
facility: Westmead
city: Aalborg
country: Denmark
facility: Department og Hematology, Aalborg University Hospital
city: Aarhus
country: Denmark
facility: Department of Hematology, Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Clinic of Hematology L-4241, Rigshospitalet
city: Esbjerg
country: Denmark
facility: Sydvestjysk Sygehus
city: Holstebro
country: Denmark
facility: Regionshospitalet Holstebro
city: Odense
country: Denmark
facility: Department of Hematology X, Odense University Hospital
city: Roskilde
country: Denmark
facility: Department of Hematology, Zeeland University Hospital Roskilde
city: Vejle
country: Denmark
facility: Vejle Sygehus
city: Helsinki
country: Finland
facility: Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center
city: Kuopio
country: Finland
facility: Kuopio University Hospital
city: Oulu
country: Finland
facility: Oulu University Hospital
city: Tampere
country: Finland
facility: Tampere University Hospital
city: Turku
country: Finland
facility: Turku University Hospital
city: Aviano
country: Italy
facility: Centro di riferimento oncologico di Aviano
city: Bari
country: Italy
facility: Istituto Tumori "Giovanni Paolo II" I.R.C.C.S Bari
city: Calabria
country: Italy
facility: The G.O.M. Bianchi-Melacrino-Morelli in Reggio Calabria
city: Monza
country: Italy
facility: Ospedale San Gerardo di Monza
city: Napoli
country: Italy
facility: Azienda Ospedaliera Univeristaria Federico II di Napoli
city: Napoli
country: Italy
facility: Istituto Nazionale Tumori "Fondazione Pascale" Napoli
city: Roma
country: Italy
facility: Azienda Ospedaliera San Camillo Forlanini di Roma
city: Segrate
country: Italy
facility: IRCCS San Raffaele Scientific Institute
city: Trieste
country: Italy
facility: Azienda Sanitaria Universitaria Integrata di Trieste
city: Turin
country: Italy
facility: AOU San Luigi Gonzaga - Orbassano University of Turin
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata di Udine
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata Verona
city: Grafton
country: New Zealand
facility: Auckland City Hospital
city: Wellington
country: New Zealand
facility: Wellington Blood and Cancer Centre
city: Bergen
country: Norway
facility: Haukeland Universitetshospital
city: Grålum
country: Norway
facility: Kalnes Hospital (Østfold)
city: Innlandet
country: Norway
facility: Sykehuset Innlandet
city: Oslo
country: Norway
facility: Akershus University Hospital
city: Oslo
country: Norway
facility: Avd. for Kreftbehandling, Oslo universitetssykehus
city: Stavanger
country: Norway
facility: Avdeling for Blod- og Kreftsykdommer, Stavanger Universitetssykehus
city: Trondheim
country: Norway
facility: Kreftklinikken, St Olavs Hospital
city: Tønsberg
country: Norway
facility: Sykehuset i Vestfold
city: Borås
country: Sweden
facility: Medicinkliniken, Södra Älvsborg Sjukhus
city: Göteborg
country: Sweden
facility: Department of Hematology and Coagulation, Sahlgrenska University Hospital
city: Halmstad
country: Sweden
facility: Department of Medicine, Halmstad Country Hospital
city: Kalmar
country: Sweden
facility: Department of Internal Medicine, Kalmar County Hospital
city: Linköping
country: Sweden
facility: Hematologiska Kliniken, Universitetssjukhuset
city: Lund
country: Sweden
facility: Department of Oncology, Skåne University Hospital
city: Stockholm
country: Sweden
facility: Center of Hematology, Karolinska University Hospital
city: Södra Sunderbyn
country: Sweden
facility: Department of Medicine, Sunderbyn Hospital
city: Uddevalla
country: Sweden
facility: Uddevalla Sjukhus
city: Umeå
country: Sweden
facility: Cancercentrum, Norrlands universitetsjukhus
city: Uppsala
country: Sweden
facility: Department of Oncology, Uppsala Academic Hospital
city: Varberg
country: Sweden
facility: Varberg Hospital
city: Örebro
country: Sweden
facility: Department of Oncology, Örebro University Hospital
Study officials:
affiliation: Department of Oncology, Skåne University Hospital
name: Mats Jerkeman
role: PRINCIPAL_INVESTIGATOR
References: