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

Diffuse Large B Cell Lymphoma Clinical Trial

— POLAR BEAR  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04332822
• Other study ID #: NLG-LBC7 POLAR BEAR
• Status: Recruiting
• Phase: Phase 3
• Start date: August 19, 2020
• Est. completion date: December 28, 2028

Study information

• Verified date: February 2024
• Source: Nordic Lymphoma Group
• Contact: Mats Jerkeman
• Phone: 0046704973507
• Email: mats.jerkeman[@]med.lu.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 28, 2028
• Est. primary completion date: December 28, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 75 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Diffuse Large B Cell Lymphoma
• DLBCL
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Large B-Cell, Diffuse

Intervention

Drug:
• R-pola-mini-CHP
Rituximab 375 mg/m2 iv, day 1, cycle 1. 1400 mg s c OR 375 mg/m2 iv cycles 2-6 Cyclophosphamide 400 mg/m2 iv, day 1, cycles 1-6 Doxorubicin 25 mg/m2 iv , day 1, cycles 1-6 Prednisone, 40 mg/m2 po, days 1-5, cycles 1-6 - round up to nearest 25 mg Polatuzumab vedotin 1.8 mg/kg iv day 1 cycles 1-6
• R-mini-CHOP
Rituximab 375 mg/m2 i.v., day 1, cycle 1. 1400 mg s c OR 375 mg/m2 i. v. cycles 2-6 Cyclophosphamide 400 mg/m2 i.v., day 1, cycles 1-6 Doxorubicin 25 mg/m2 i.v., day 1, cycles 1-6 Vincristine 1 mg i.v. (total dose), day 1, cycles 1-6 Prednisone, 40 mg/m2 p.o, days 1-5, , cycles 1-6

Locations

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

Sponsors (2)

Lead Sponsor	Collaborator
Nordic Lymphoma Group	Roche Pharma AG

Countries where clinical trial is conducted

Australia,  Denmark,  Finland,  Italy,  New Zealand,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free survival (PFS).	Interval between randomization date and date of documented progression, first relapse, or death of any cause	2 years.