Clinical Trials Register

Summary
EudraCT Number:	2017-003149-56
Sponsor's Protocol Code Number:	OLYMP-1
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2018-01-10
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Germany - PEI

A.2

EudraCT number

2017-003149-56

A.3

Full title of the trial

OBINUTUZUMAB in MARGINAL ZONE LYMPHOMA

Obinutuzumab bei Marginalzonen-Lymphomen

A.3.1

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

OBINUTUZUMAB in MARGINAL ZONE LYMPHOMA

Obinutuzumab bei Marginalzonen-Lymphomen

A.4.1

Sponsor's protocol code number

OLYMP-1

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT03322865

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	University Hospital Ulm
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	Roche Pharma AG
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	University Hospital Ulm
B.5.2	Functional name of contact point	Prof. Dr. med. Christian Buske
B.5.3	Address:
B.5.3.1	Street Address	Albert-Einstein-Allee 23
B.5.3.2	Town/ city	Ulm
B.5.3.3	Post code	89081
B.5.3.4	Country	Germany
B.5.4	Telephone number	+4973150065800
B.5.5	Fax number	+4973150065802
B.5.6	E-mail	christian.buske@uni-ulm.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	Gazyvaro
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Pharma AG
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	Obinutuzumab
D.3.2	Product code	RO5072759/F06-01
D.3.4	Pharmaceutical form	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	Obinutuzumab
D.3.9.1	CAS number	949142-50-1
D.3.9.3	Other descriptive name	OBINUTUZUMAB
D.3.9.4	EV Substance Code	SUB32751
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1000
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	Yes
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	Yes
D.3.11.13.1	Other medicinal product type	Obinutuzumab is a humanized and glyco-engineered monoclonal antibody

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

Marginal Zone Lymphoma

Marginalzonen Lymphome

E.1.1.1

Medical condition in easily understood language

Marginal Zone Lymphoma

Marginalzonen Lymphome

E.1.1.2

Therapeutic area

Diseases [C] - Cancer [C04]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.0
E.1.2	Level	PT
E.1.2	Classification code	10062113
E.1.2	Term	Splenic marginal zone lymphoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10076596
E.1.2	Term	Marginal zone lymphoma
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

The objective of the trial is to test the efficacy and toxicity of first line treatment with single agent Obinutuzumab in patients with MZoL in need of treatment, who have failed or are not eligible for local therapy.

E.2.2

Secondary objectives of the trial

• Progression free survival
• OR rates, PR rates
• Duration of response
• Time to first response
• Time to best response under treatment (induction and maintenance)
• Time to next anti-lymphoma therapy and time to next chemotherapy based treatment
• Treatment associated adverse events
• Quality of life during induction and maintenance therapy
• Cumulative incidence of secondary malignancies
• Cumulative incidences of disease related death
• Overall survival

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Patients must have a proven pathological diagnosis of MZoL, diagnosed by a reference pathology center.
Patients must meet all of the following inclusion criteria to be eligible for participation in this study:
Confirmed CD20 positive de novo MALT Lymphoma following or being not eligible for local therapy (including surgery, radiotherapy) and antibiotics e.g. for H. pylori-positive gastric lymphoma arisen at any extranodal site
OR Confirmed CD20 positive de novo splenic MZoL following or not being eligible for local therapy (including surgery and antiviral therapy for Hepatitis C Virus) with symptomatic disease
OR Confirmed CD20 positive de novo nodal MZoL following or not being eligible for local therapy (radiotherapy)
For patients with symptomatic splenic, nodal, or non-gastric extranodal MZoL disease that is de novo or has relapsed following local therapy (i.e., surgery or radiotherapy) and requires therapy, as assessed by the investigator.
For patients with symptomatic gastric extranodal MZoL: Helicobacter pylori-negative disease that is de novo or has relapsed following local therapy (i.e., surgery or radiotherapy) and requires therapy, as assessed by the investigator, or H. pylori–positive disease that has remained stable, progressed, or relapsed following antibiotic therapy and requires therapy, as assessed by the investigator
– At least one bi-dimensionally measurable lesion (≥ 1.5 cm in its largest dimension by CT scan or MRI).
For an enlarged liver to constitute the only measurable disease parameter, a liver biopsy showing proof of NHL in the liver is required.
For SMZL:
In patients with splenic MZoL, an enlarged spleen on CT scan or extending at least 2 cm below the costal margin by physical examination will constitute measurable disease providing that no explanation other than lymphomatous involvement is likely.
At least one of the following must be met:
– Bulky progressive or painful splenomegaly
– one of the following symptomatic/progressive cytopenias : Hb < 10 g/dL, or Plat < 80.000 /µL, or neutropenia < 1000 /µL, whatever the reason (autoimmune or hypersplenism or bone marrow infiltration)
– enlarged lymphoadenopathy or involvement of extranodal sites with or without cytopenia
– splenectomised patients with rapidly raising lymphocyte counts, development of lymphadenopathy or involvement of extranodal sites
– SMZL with concomitant hepatitis C infection who have not responded to or are relapsed after Interferon and/or Ribavirin (patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
For gastric MALT Lymphoma:
– H. pylori-negative disease de novo or following or being not eligible for local therapy (i.e., surgery, radiotherapy or antibiotics).
– H. pylori–positive disease that has remained stable, progressed, or relapsed following antibiotic therapy.

E.4

Principal exclusion criteria

– ECOG performance status >2
– History of a non-lymphoid malignancy except for the following: adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, asymptomatic prostate cancer without known metastatic disease and with no requirement for therapy or requiring only hormonal therapy and with normal prostate specific antigen for ≥1 year prior to study enrollment visit, other Stage 1 or 2 cancer treated with a curative intent and currently in complete remission, for ≥3 years.
– Central nervous system lymphoma, leptomeningeal lymphoma, or histologic evidence of transformation to a high-grade or diffuse large B-cell lymphoma.
– Ongoing immunosuppressive therapy including corticosteroids (exception < 4 weeks administered at a dose equivalent to <=40 mg/day prednisone is allowed)
– Evidence of ongoing systemic bacterial, fungal, or viral infection at the time of study enrollment visit
– Ongoing drug-induced liver injury, chronic active hepatitis B (HBV), alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis, extrahepatic obstruction caused by cholelithiasis, cirrhosis of the liver, or portal hypertension.
– Ongoing alcohol or drug addiction
– Breastfeeding or pregnancy
– Prior or ongoing clinically significant illness, medical condition, surgical history, physical finding, electrocardiogram (ECG) finding, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject or impair the assessment of study results.
– History of anaphylaxis in association with previous administration of monoclonal antibodies.
– Vaccination with a live vaccine within 28 days prior to start of therapy
– Treatment with any other investigational agent within 30 days or within 5 x the half-life (t1/2) of the investigational product, whichever is longer, or participating in another trial within 30 days prior to entering this study.

E.5 End points

E.5.1

Primary end point(s)

CR rate (CRR) (determined after induction therapy)

E.5.1.1

Timepoint(s) of evaluation of this end point

Determined after induction therapy

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

Induction and Maintenance

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.8.3

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

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

Yes

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

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.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)

Further treatment is in the discretion of the treating physician

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	German Lymphoma Alliance-GLA
G.4.3.4	Network Country	Germany

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2018-03-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-05-14

P. End of Trial
P.	End of Trial Status	Ongoing

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