Clinical Trials Register

Summary
EudraCT Number:	2014-005069-60
Sponsor's Protocol Code Number:	P000798
National Competent Authority:	Austria - BASG
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-02-22
Trial results	View 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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Austria - BASG

A.2

EudraCT number

2014-005069-60

A.3

Full title of the trial

R-CPOP as first line therapy for elderly patients with DLBCL and for patients with limited cardiac function with DLBCL

A.3.1

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

R-CPOP (Rituximab plus Cyclophosphamid, Pixantron, Vincristin, Prednison) as first line therapy for elderly patients with diffuse-large B cell lymphoma (DLBCL) and for patients with limited cardiac function with DLBCL

R-CPOP (Rituximab plus Cyclophosphamid, Pixantron, Vincristin, Prednison) als Erstlinientherapie für ältere Patienten mit diffus großzelligem B-Zell-Lymphom (DLBCL) und für Patienten mit eingeschränkter Herzfunktion mit DLBCL

A.3.2

Name or abbreviated title of the trial where available

Pix in DLBCL first line

A.4.1

Sponsor's protocol code number

P000798

A.5.4

Other Identifiers

Name:

DRKS-Number

Number:

DRKS00000718

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	Medical Center - University of Freiburg
B.1.3.4	Country	Germany
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	Servier Affaires Médicales
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medical Center - University of Freiburg
B.5.2	Functional name of contact point	Clinical Trials Unit
B.5.3	Address:
B.5.3.1	Street Address	Elsaesser Str. 2
B.5.3.2	Town/ city	Freiburg
B.5.3.3	Post code	79110
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49761270-73800
B.5.5	Fax number	+49761270-74250
B.5.6	E-mail	andrea.kunzmann@uniklinik-freiburg.de

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	Pixuvri®
D.2.1.1.2	Name of the Marketing Authorisation holder	CTI Life Sciences Limited
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.3.4	Pharmaceutical form	Powder for concentrate 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	Pixantrone
D.3.9.1	CAS number	144510-96-3
D.3.9.3	Other descriptive name	PIXANTRONE
D.3.9.4	EV Substance Code	SUB21304
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	5.8
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 (DLBCL)

E.1.1.1

Medical condition in easily understood language

A subtype of non-Hodgkin lymphoma, a tumour disease involving B lymphocytes, a particular type of white blood cells with a key role in immune system

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assessment of rate of complete remission after induction therapy

E.2.2

Secondary objectives of the trial

Assessment of:
overall survival, progression-free survival,
cardiac toxicity, and
safety

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Written informed consent obtained according to international guidelines and local laws
2. Male or female patients aged ≥ 18 years without upper age limit
3. Previously untreated and histologically confirmed diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma grade 3B according to REAL/WHO classification
4. At least one objectively bi-dimensionally measurable lesion as demonstrated by CT, spiral CT, or MRI that can be followed for response as target lesion; patients with the following sites of disease are NOT eligible:
- Patients with only skin lesions or only palpable lymph nodes
- Patients with spleen or bone marrow as only site of disease
5. Life expectancy ≥ 3 months according to investigator´s opinion
6. Ann Arbor stage: II-IV
7. Ability to understand the nature of the trial and the trial-related procedures and to comply with them
8. Criteria for stratification:
Population 1:
Age ≥ 75 years (without limited cardiac function) not eligible for standard R-CHOP 21 treatment
or
Population 2:
Impaired cardiac function, characterised by:
First 10 patients:
Ejection fraction: ≥ 40% and ≤ 50%

Additional patients:
Ejection fraction: > 30% and ≤ 50%

Note: Patients ≥ 75 years of age with impaired cardiac function are eligible for population 2.

E.4

Principal exclusion criteria

1. Severe pulmonary, hepatic or renal comorbidities which make the patient ineligible for cytotoxic drug treatment
2. Severe cardiac impairment, e.g. NYHA class IV, (with the exception of inclusion criterion 8), or resting cardiac troponin T levels >0.05 ng/ml (according to > grade 1 CTCAE 3.0) which makes the patient ineligible for cytotoxic drug treatment
3. Prior treatment for lymphoma other than pre-treatment with steroids
4. History of indolent lymphoma
5. Manifestation of DLBCL disease in central nervous system (CNS)
6. Active hepatitis B or C, serologic positivity for HIV infection
7. HIV-related lymphoma
8. Immunisation with live virus vaccines within the last 14 days
9. Major thoracic and/or abdominal surgery within the 4 weeks before trial registration from which the patient has not fully recovered except for diagnosis of non-Hodgkin lymphoma (NHL); patients who have had minor surgery may be enrolled after a ≥ 1 week recovery period except for diagnosis of NHL
10. Serious (NCI CTCAE grade 3-4) intercurrent infection at the time of trial registration or deep-seated or systemic mycotic infection.
11. Active or history of another malignancy except cured basal cell carcinoma of skin or carcinoma in situ of uterine cervix; patients who have been in remission from another previous malignancy for > 5 years will be considered eligible
12. Known hypersensitivity to pixantrone, or any drugs or excipients of the associated chemotherapy R-CPOP that the patient will receive
13. Simultaneous participation in other interventional trials and/or participation before the end of a required restriction period
14. Participation in a clinical trial within the last 30 days before being registered in this trial
15. Known or persistent abuse of medication, drugs or alcohol
16. Person who is in a relationship of dependence/employment with the sponsor or the investigator
17. For female patients of child-bearing potential: current or planned pregnancy, nursing period
18. Unwillingness to use an adequate contraception method during chemotherapy treatment until six months thereafter:
for male patients (unless vasectomised):
18.1 a latex condom during sexual contact with females of childbearing potential
for female patients of child-bearing potential:
18.2 mechanical method (female condom, diaphragm or coil) used in combination with a spermicide; hormonal intra-uterine device or hormonal contraception in combination with a mechanical method of contraception

E.5 End points

E.5.1

Primary end point(s)

Rate of complete remission after induction therapy as determined by PET-CT 6 weeks after last treatment (EOT visit)

E.5.1.1

Timepoint(s) of evaluation of this end point

End of treatment visit

E.5.2

Secondary end point(s)

Overall survival:
time from start of trial treatment to death from any cause, considering patients, where the event of interest has not been observed, as censored observations.

Progression-free survival:
time from start of trial treatment to disease progression or death from any cause, whichever occurs first. Patients for whom the event of interest has not been observed are analysed as censored observations.

Cardiac toxicity:
echocardiography, ECG, troponin T, NT-proBNP during chemotherapy, at end of treatment and every 3 or 6 months during follow up;
cardiac AEs according to CTCAE

Safety:
Rates of adverse events and serious adverse events according to CTCAE

E.5.2.1

Timepoint(s) of evaluation of this end point

endpoints:
Overall survival: continuously during treatment and follow-up
Progression-free-survival: continuously during treatment and follow-up
Cardiac toxicity: continuously during treatment and follow-up
Safety: continously during treatment phase

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

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

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)

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

Yes

E.8.4

The trial involves multiple sites in the 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

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)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

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

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)

according to the investigator's discretion based on best standard of care

G. Investigator Networks to be involved in the Trial

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2017-04-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-05-09

P. End of Trial
P.	End of Trial Status	Completed

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials