Clinical Trials Register

Summary
EudraCT Number:	2018-003889-14
Sponsor's Protocol Code Number:	NLG-LBC7
National Competent Authority:	Norway - NOMA
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2020-03-24
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Norway - NOMA

A.2

EudraCT number

2018-003889-14

A.3

Full title of the trial

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 - NLG-LBC7

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.3.2

Name or abbreviated title of the trial where available

POLAR BEAR

A.4.1

Sponsor's protocol code number

NLG-LBC7

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Skåne University Hospital, Department of Oncology
B.1.3.4	Country	Sweden
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Skåne University Hospital, Dept. of Oncology
B.4.2	Country	Sweden
B.4.1	Name of organisation providing support	Roche AB, Box 1228, 171 23 Solna
B.4.2	Country	Sweden
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Nordic Lymphoma Group, Dept. of Haematology
B.5.2	Functional name of contact point	Clinical Trial Office
B.5.3	Address:
B.5.3.1	Street Address	Palle Juul-Jensens Boulevard 99, C104
B.5.3.2	Town/ city	Aarhus
B.5.3.3	Post code	DK - 8200
B.5.3.4	Country	Denmark
B.5.4	Telephone number	+45 7845 5855
B.5.5	Fax number	+45 7846 7597
B.5.6	E-mail	a-cto@auh.rm.dk

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Polivy
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration GmbH
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	polatuzumab vedotin
D.3.4	Pharmaceutical form	Powder for solution for infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	POLATUZUMAB VEDOTIN
D.3.9.2	Current sponsor code	F. Hoffman la Roche
D.3.9.4	EV Substance Code	SUB177827
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	1.8 to 1.0
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Vincristine
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Vincristine
D.3.4	Pharmaceutical form	Solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	VINCRISTINE
D.3.9.1	CAS number	57-22-7
D.3.9.3	Other descriptive name	Vincristine
D.3.9.4	EV Substance Code	SUB00059MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Diffuse large B-cell lymphoma.

E.1.1.1

Medical condition in easily understood language

Diffuse large B-cell lymphoma.

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	LLT
E.1.2	Classification code	10012857
E.1.2	Term	Diffuse large cell lymphoma (Diffuse large B-cell lymphoma) (Working Formulation) refractory
E.1.2	System Organ Class	100000004864

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective is to evaluate if progression-free survival with pola-R-mini-CHP is superior to that of R-mini-CHOP.

E.2.2

Secondary objectives of the trial

To compare response duration, complete remission rate (CR), overall response rate (ORR), health-related quality of life (HRQOL), lymphoma specific survival (LSS), overall survival (OS), and safety between these regimens.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Age ≥80 years or frail ≥75 years, according to simplified comprehensive geriatric assessment

2. Histologically confirmed lymphoma belonging to one of the following subtypes:
a. diffuse large B-cell lymphoma, including transformation from an indolent lymphoma
b. follicular lymphoma grade 3B
c. T-cell/histiocyte-rich LBCL
d. primary cutaneous DLBCL, leg type
e. EBV-positive DLBCL, NOS
f. primary mediastinal LBCL
g. high grade B-cell lymphoma with MYC/BCL2 rearrangement

3. Stage II-IV disease

4. At least 1 measurable site of disease (>1.5 cm long axis)

5. No previous treatment for lymphoma

6. WHO performance status 0 – 3 (Grade 3 if related to DLBCL)

7. Written informed consent

E.4

Principal exclusion criteria

1. Severe cardiac disease: NYHA grade 3-4

2. CNS involvement at diagnosis

3. Uncontrolled serious infection

4. 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

5. Absolute neutrophil count (ANC) <1000 cells/mcL or platelets <100,000 cells/mcL, unless due to lymphoma

6. 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

7. Psychiatric illness or condition which could interfere with their ability to understand the requirements of the study

8. Known hypersensitivity to rituximab, polatuzumab vedotin, cyclophosphamide, vincristine or doxorubicin, or to additives in the formulations above, or known hypersensitivity to other human, humanized, chimeric or porcine monoclonal antibodies, or HACA against rituximab

9. Peripheral neuropathy grade ≥ 2

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival:
This is defined as the interval between randomization date and date of documented progression, first relapse, or death of any cause. Otherwise, patients will be censored at the last date they were known to be alive.

E.5.1.1

Timepoint(s) of evaluation of this end point

Timepont of evaluation is when the last patient included in the study has been followed for a minimum of 2 years

E.5.2

Secondary end point(s)

Overall survival:
This is defined as time from registration to death of any cause. Patients still alive or lost to follow-up are censored at the last date they were known to be alive.

Lymphoma specific survival:
This is defined as the time interval from inclusion in the study to lymphoma associated death and will be censored at the latest follow-up date in patients alive.

Response duration:
Duration of best response from time of response assessment to progression or lymphoma associated death

Complete remission rate (CR): Number and fraction of patients included achieving a CR.
Overall remission rate: Number and fraction of patients included achieving a complete or partial remission.

Health related quality of life (HRQOL) will be assessed through patient recorded questionnare EORTC-QLQ-C30
Safety through Collection of adverse events and serious adverse events

E.5.2.1

Timepoint(s) of evaluation of this end point

Timepont of evaluation of efficacy endpoints (overall survival, lymphoma specific survival, overall remission rate, response duration) is when the last patient included in the study has been followed for a minimum of 2 years.

Evaluation of adverse and serious adverse events will be performed when the first 50 patients have been followed for a minimum of 3 months and further throughout the study when deemed necessary. Evaluation of these events will be recorded for the entire study population at the same time as the efficacy assessments.

Health related quality of life (HRQOL) will be recorded when the last patient included has been followed for at least 12 months after end of treatment.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

200

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

200

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Nordic Lymphoma Group
G.4.3.4	Network Country	Denmark

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-06-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-05-19

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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