Clinical Trials Register

Summary
EudraCT Number:	2010-018780-42
Sponsor's Protocol Code Number:	OMB113676
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2010-07-02
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

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A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2010-018780-42

A.3

Full title of the trial

Phase III Randomized, Open Label Study of Single Agent Ofatumumab Vs. Single Agent Rituximab in Indolent B-Cell Non Hodgkin Lymphoma Relapsed After Rituximab-Containing Therapy

A.3.1

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

Phase III Randomized, Open Label Study of Single Agent Ofatumumab Vs. Single Agent Rituximab in Follicular Lymphoma Releapsed After Rituximab-Containing Therapy

A.4.1

Sponsor's protocol code number

OMB113676

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	GlaxoSmithKline Research & Development Limited
B.1.3.4	Country	United Kingdom
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GlaxoSmithKline Research and Development Limited
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline Research & Development Ltd
B.5.2	Functional name of contact point	Clinical Trials Helpdesk
B.5.3	Address:
B.5.3.1	Street Address	Iron Bridge Road, Stockley Park west
B.5.3.2	Town/ city	Uxbridge, Middlesex
B.5.3.3	Post code	UB11 - 1BU
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 0208 990 44 66
B.5.5	Fax number	+440208 990 12 34
B.5.6	E-mail	GSKClinicalSupportHD@gsk.com

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	Arzerra
D.2.1.1.2	Name of the Marketing Authorisation holder	Glaxo Group 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	Yes
D.2.5.1	Orphan drug designation number	EU/3/08/581
D.3 Description of the IMP
D.3.1	Product name	ofatumumab
D.3.2	Product code	ofatumumab
D.3.4	Pharmaceutical form	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	ofatumumab
D.3.9.2	Current sponsor code	GSK1841157
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	20
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	Monoclonal antibody
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	MabThera
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Products Ltd
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	MabThera
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	RITUXIMAB
D.3.9.1	CAS number	174722-31-7
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	10
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	Yes
D.3.11.13.1	Other medicinal product type	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

Indolent B-Cell Non-Hodgkin's Lymphoma

E.1.1.1

Medical condition in easily understood language

Patients will have a certain type of slow-growing cancer of the lymph nodes called follicular lymphoma.

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

To compare progression-free survival following therapy with single agent ofatumumab versus single agent rituximab in subjects with iNHL that has relapsed after prior rituximab-containing therapy.

E.2.2

Secondary objectives of the trial

•Compare complete response, overall response, duration of response, time to next treatment, and overall survival following salvage therapy with single agent ofatumumab versus single agent rituximab in subjects with iNHL that has relapsed after prior rituximab-containing therapy.
•Compare grade 3-4 infusion toxicity, hematologic toxicity and infectious toxicity following salvage therapy with single agent
ofatumumab versus single agent rituximab in subjects with iNHL that has relapsed after prior rituximab-containing therapy.
•To determine the effect of FCGR3A and FCGR2A polymorphisms on response rates and median progression-free survival following salvage therapy with single agent ofatumumab in subjects with iNHL that has relapsed after prior rituximab-containing therapy, and to compare response rates and median progression-free survival with ofatumumab versus rituximab in patients with low affinity FCGR polymorphisms.
•To determine PK of ofatumumab in subjects with relapsed iNHL.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Indolent NHL subtypes defined according to World Health Organization guidelines:
a. Follicular lymphoma Grades 1, 2, 3 A
o Follicular lymphoma Grade 3B (absence of centrocytes) is not eligible for this study.
o The histology and CD20 expression on tumor cells must be verified by pathology review of a current or previous tissue biopsy.
b. Small lymphocytic lymphoma (SLL)
o Subjects with a diagnosis of SLL who have a peripheral blood monoclonal B lymphocyte count of ≥5,000 cells/μL are considered to
have CLL and are not eligible for this study.
c. Marginal zone lymphoma
d. Lymphoplasmacytic lymphoma
2. Rituximab-sensitive iNHL, defined as a partial or complete response to their last prior treatment with rituximab or a rituximab-containing regimen lasting at least 6 months
following completion of rituximab treatment.
3. Relapse or disease progression following response to prior rituximab-based therapy, as defined by 2007 RRCML criteria, which requires therapy.
4. Radiographically measurable disease, defined as:
• 2 or more clearly demarcated lesions/nodes with a long axis >1.5 cm and short axis ≥1.0cm
OR
• 1 clearly demarcated lesion/node with a long axis >2.0 cm and short axis ≥1.0cm
5. ECOG Performance Status of 0, 1, or 2.
6. Age ≥ 18 years.
7. Life expectancy of at least 6 months in the opinion of the investigator.
8. The patient or their legally acceptable representative must be capable of giving written informed consent prior to performing any study-specific tests or procedures.
9. All prior treatment related non-hematologic toxicities (with the exception of alopecia) must have resolved to CTCAE (Version 4.0) ≤ Grade 2 at the time of randomization. (Hematologic parameters are discussed in Section 4.1.3 point 11.)
10. One or more of the following indications for treatment:
a) Cytopenias.
b) One or more of the following lymphoma-related symptoms:
• Night sweats without signs of infection
• Unintentional weight loss ≥ 10% within the previous 6 months
• Recurrent, unexplained fever of greater than 100.5°F (38°C) without
signs of infection
• Fatigue which interferes with the patient's quality of life
c) Progressive or massive lymphadenopathy
OR
d) Progressive or massive organomegaly
Specific information regarding warnings, precautions, contraindications, adverse events,
and other pertinent information on the study treatment(s) that may impact subject eligibility is provided in the Investigator Brochure.
French subjects: In France, a subject will be eligible for inclusion in this study only if
either affiliated to or a beneficiary of a social security category.

E.4

Principal exclusion criteria

1. Previous treatment with ofatumumab.
2. Previous anti-CD20 radioimmunotherapy (RIT), or non-rituximab anti-CD20 therapy (such as obinutuzumab) within 6 months prior to randomization. Patients
who have received previous anti-CD20 RIT or non-rituximab anti-CD20 therapy (such as obinutuzumab) must have attained a partial or complete response
lasting at least 6 months, and must have recovered from any hematologic or other toxicity.
3. Previous autologous stem cell transplantation within 6 months prior to randomization.
4. Previous allogeneic stem cell transplantation.
5. Previous anti-lymphoma monoclonal antibody therapy (excluding anti-CD20 therapy and anti-CD20 RIT), chemotherapy, glucocorticoid, or other systemic therapy for lymphoma within 3
months prior to randomization.
6. Current or previous participation in the treatment phase of another interventional clinical study within 4
weeks prior to randomization. Patients may continue in the follow-up phase of another interventional clinical study, but may not have undergone any treatment on the other study within 4 weeks prior to randomization.
7. Current or previous other malignancy within 2 years prior to randomization. Subjects who
have been free of malignancy for at least 2 years, or have a history of completely resected non-melanoma skin cancer or successfully treated carcinoma in situ, are eligible.
8. Chronic or current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis, active Hepatitis C, and
known HIV disease. All HIV-positive patients are excluded from this study,
regardless of whether they have an Acquired Immunodeficiency Syndrome (AIDS) defining disease and/or are on antiviral therapy. Prophylactic antiviral and/or antibacterial antibiotics to prevent recurrence of previous infections are permitted.
9. Clinically significant cardiac disease as judged by the investigator including unstable angina, acute myocardial infarction within 6 months prior to randomization, uncontrolled congestive
heart failure, and uncontrolled arrhythmia. Subjects with congestive heart disease or arrhythmias such as atrial fibrillation whose cardiac disease is well controlled on a stable medical regimen are eligible.
10. Other significant concurrent, uncontrolled medical conditions including, but not limited to, renal, hepatic, autoimmune, hematological, gastrointestinal, endocrine,
pulmonary, neurological, cerebral or psychiatric disease which, in the investigator’s
opinion, will impact study participation.
11. Screening laboratory values:
a. Neutrophils < 1.5 x 10^9/L (unless due to FL involvement of the bone marrow).
b. Platelets < 50 x 10^9/L (unless due to FL involvement of the bone marrow).
c. ALT or AST > 3xULN
d. Alkaline phosphatase > 1.5xULN (unless due to lymphoma or a non-malignant, non-hepatic cause such as Paget’s disease)
e. Total bilirubin > 1.5xULN (unless due to lymphoma or isolated, predominantly indirect hyperbilirubinemia due to Gilbert’s syndrome)
12. Known or suspected inability to fully comply with study protocol
13. Because the effects of ofatumumab on fetuses and nursing infants are not known, the
following are ineligible for study entry:
a. Lactating women.
b. Women with a positive pregnancy test at study entry
c. Men with partners of childbearing potential and women of childbearing potential
who are not willing to use adequate contraception from study entry through one
year following last treatment dose. (Adequate contraception is defined as
abstinence, oral hormonal birth control, hormonal birth control injections,
implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive
patches, intrauterine device, and male partner sterilization if male partner is the
sole partner for a female subject. The double barrier method can be used in
regions where considered acceptable and adequate, defined as condom or
occlusive cap plus spermicidal agent).
14. Current active liver or biliary disease (with the exception of Gilbert’s syndrome or asymptomatic gallstones).
15. Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a
HB DNA test will be performed and if positive the subject will be excluded.
- Consult with a physician experienced in care & management of subjects with hepatitis B to manage/treat subjects who are anti-HNc positive

E.5 End points

E.5.1

Primary end point(s)

Progression-free survival (PFS), defined as the interval between randomization and disease progression or death due to any cause.

E.5.1.1

Timepoint(s) of evaluation of this end point

Tests will be carried out to establish the patients response to treatment and therefore Primary Endpoint at weeks 12, 28 and 44.

E.5.2

Secondary end point(s)

1. Complete response (CR) rate, using modified 2007 Revised Response Criteria for Malignant Lymphoma (RRCML).
2. Overall response (OR) rate (OR = CR + partial response (PR) rate).
3. Duration of response in patients achieving PR or CR.
4. Time to next treatment (TNT).
5. Overall survival (OS), defined as the interval between randomisation and death due to any cause.
6. Grade 3-4 infusion toxicity, hematologic toxicity and infectious toxicity.
7. Effect of FCGR3A and FCGR2A polymorphisms on median PFS, CR and OR.
8. Pharmacokinetics of ofatumumab.
9. Median PFS, CR and OR by FLIPI-1 and FLIPI-2 prognostic groups.

E.5.2.1

Timepoint(s) of evaluation of this end point

Pharmacogenetics Efficacy Endpoint: To determine the effect of FCGR3A and FCGR2A polymorphisms on response rates and median PFS following therapy with single agent ofatumumab vs. single agent rituximab in subjects with follicular lymphoma that has relapsed after prior rituximab-containing therapy.

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

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

Yes

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

Yes

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

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

The end of the trial is defined as last patient to complete last follow-up visit

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)

Yes

F.1.2.1

Number of subjects for this age range:

155

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

361

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Written consent will be obtained from each subject or their legally acceptable representative prior to participation in the study.

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

200

F.4.2.2

In the whole clinical trial

516

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)

Post study treatment will not be provided as part of the protocol. Every effort should be made to complete the required withdrawal evaluations prior to initiating further anticancer therapy or dosing of an investigational agent (see Table 4 of the Protocol for follow-up assessments and procedures).
The investigator is responsible for ensuring that consideration has been given to the poststudy care of the patient’s medical condition.

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

2010-08-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-10-21

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2016-12-19

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