POLAR BEAR: 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

Sponsor

Nordic Lymphoma Group (Other)

Overall Status

Recruiting

CT.gov ID

NCT04332822

Collaborator

Roche Pharma AG (Industry)

200

Enrollment

Locations

Arms

66.3

Anticipated Duration (Months)

4.4

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a phase III, randomized, open-label, multicenter trial, conducted in Sweden, Norway, Finland, Denmark, Italy and Switzerland, 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 2026.

Condition or Disease	Intervention/Treatment	Phase
DLBCL Diffuse Large B Cell Lymphoma	Drug: R-pola-mini-CHP Drug: R-mini-CHOP	Phase 3

Study Design

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Aug 19, 2020

Anticipated Primary Completion Date :

Feb 28, 2023

Anticipated Study Completion Date :

Feb 28, 2026

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm A - R-mini-CHOP Cycles 1-6, duration 21 days 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	Drug: 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
Experimental: Arm B - R-pola-mini-CHP Cycles 1-6, duration 21 days 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 Prednisone, 40 mg/m2 p.o, days 1-5, , cycles 1-6 Polatuzumab vedotin 1.8 mg/kg i.v day 1 cycles 1-6	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

Arm

Intervention/Treatment

Active Comparator: Arm A - R-mini-CHOP

Cycles 1-6, duration 21 days 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

Drug: 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

Experimental: Arm B - R-pola-mini-CHP

Cycles 1-6, duration 21 days 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 Prednisone, 40 mg/m2 p.o, days 1-5, , cycles 1-6 Polatuzumab vedotin 1.8 mg/kg i.v day 1 cycles 1-6

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

Outcome Measures

Primary Outcome Measures

Progression-free survival (PFS). [2 years.]
The primary end point of this study is PFS. The null hypothesis is that pola-R-mini-CHP is equivalent to R-mini-CHOP. PFS is defined as the interval between registration date and date of documented progression or lack of response, first relapse, or death of any cause. Otherwise, patients will be censored at the last date they were known to be alive. For patients with PD as best response, PFS is defined as 1 day.

Eligibility Criteria

Criteria

Ages Eligible for Study:

75 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

diffuse large B-cell lymphoma, including transformation from an indolent lymphoma
follicular lymphoma grade 3B
T-cell/histiocyte-rich LBCL
primary cutaneous DLBCL, leg type
EBV-positive DLBCL, NOS
primary mediastinal LBCL
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

Contacts and Locations

Locations

	Site	City	Country
1	Department og Hematology, Aalborg University Hospital	Aalborg	Denmark
2	Department of Hematology, Aarhus University Hospital	Aarhus	Denmark
3	Clinic of Hematology L-4241, Rigshospitalet	Copenhagen	Denmark
4	Sydvestjysk Sygehus	Esbjerg	Denmark
5	Herlev Hospital	Herlev	Denmark
6	Regionshospitalet Holstebro	Holstebro	Denmark
7	Department of Hematology X, Odense University Hospital	Odense	Denmark
8	Department of Hematology, Zeeland University Hospital Roskilde	Roskilde	Denmark
9	Vejle Sygehus	Vejle	Denmark
10	Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center	Helsinki	Finland
11	Kuopio University Hospital	Kuopio	Finland
12	Oulu University Hospital	Oulu	Finland
13	Tampere University Hospital	Tampere	Finland
14	Turku University Hospital	Turku	Finland
15	Centro di riferimento oncologico di Aviano	Aviano	Italy
16	Istituto Tumori "Giovanni Paolo II" I.R.C.C.S Bari	Bari	Italy
17	Ospedale San Gerardo di Monza	Monza	Italy
18	Azienda Ospedaliera Univeristaria Federico II di Napoli	Napoli	Italy
19	Istituto Nazionale Tumori "Fondazione Pascale" Napoli	Napoli	Italy
20	Azienda Ospedaliera San Camillo Forlanini di Roma	Roma	Italy
21	IRCCS San Raffaele Scientific Institute	Segrate	Italy
22	Azienda Sanitaria Universitaria Integrata di Trieste	Trieste	Italy
23	Azienda Sanitaria Universitaria Integrata di Udine	Udine	Italy
24	Azienda Ospedaliera Universitaria Integrata Verona	Verona	Italy
25	Haukeland Universitetshospital	Bergen	Norway
26	Kalnes Hospital (Østfold)	Grålum	Norway
27	Akershus University Hospital	Oslo	Norway
28	Avd. for Kreftbehandling, Oslo universitetssykehus	Oslo	Norway
29	Avdeling for Blod- og Kreftsykdommer, Stavanger Universitetssykehus	Stavanger	Norway
30	University Hospital of North Norway	Tromsø	Norway
31	Kreftklinikken, St Olavs Hospital	Trondheim	Norway
32	Sykehuset i Vestfold	Tønsberg	Norway
33	Medicinkliniken, Södra Älvsborg Sjukhus	Borås	Sweden
34	Department of Hematology and Coagulation, Sahlgrenska University Hospital	Göteborg	Sweden
35	Department of Medicine, Halmstad Country Hospital	Halmstad	Sweden
36	Department of Internal Medicine, Kalmar County Hospital	Kalmar	Sweden
37	Hematologiska Kliniken, Universitetssjukhuset	Linköping	Sweden
38	Department of Oncology, Skåne University Hospital	Lund	Sweden
39	Center of Hematology, Karolinska University Hospital	Stockholm	Sweden
40	Department of Medicine, Sunderbyn Hospital	Södra Sunderbyn	Sweden
41	Uddevalla Sjukhus	Uddevalla	Sweden
42	Cancercentrum, Norrlands universitetsjukhus	Umeå	Sweden
43	Department of Oncology, Uppsala Academic Hospital	Uppsala	Sweden
44	Varberg Hospital	Varberg	Sweden
45	Department of Oncology, Örebro University Hospital	Örebro	Sweden

Sponsors and Collaborators

Nordic Lymphoma Group
Roche Pharma AG

Investigators

Principal Investigator: Mats Jerkeman, Department of Oncology, Skåne University Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Nordic Lymphoma Group

ClinicalTrials.gov Identifier:

NCT04332822

Other Study ID Numbers:

NLG-LBC7 POLAR BEAR

First Posted:

Apr 3, 2020

Last Update Posted:

Jul 9, 2021

Last Verified:

Nov 1, 2020

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Nordic Lymphoma Group

DLBCL

Diffuse Large B Cell Lymphoma

Additional relevant MeSH terms:

Lymphoma

Lymphoma, B-Cell

Lymphoma, Large B-Cell, Diffuse

Study Results

No Results Posted as of Jul 9, 2021