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

• Register: EUCTR
• Last refreshed on: 20 February 2017
• Main ID: EUCTR2010-018780-42-CZ
• Date of registration: 02/07/2010
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Limited
• Public title: Phase III Randomized, Open Label Study of Single Agent Ofatumumab Vs. Single Agent Rituximab in Follicular Lymphoma Releapsed After Rituximab-Containing Therapy
• Scientific title: 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
• Date of first enrolment: 21/10/2010
• Target sample size: 516
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2010-018780-42
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 2
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belgium, Bulgaria, Czech Republic, France, Hungary, Slovakia

Contacts

• Name: Clinical Trials Helpdesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

• Name: Clinical Trials Helpdesk
• Affiliation: GlaxoSmithKline Research & Development Ltd

Key inclusion & exclusion criteria

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.
Are the trial subjects under 18? no
Number of subjects for this age range:
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

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 poten

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Indolent B-Cell Non-Hodgkin's Lymphoma

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Trade Name: Arzerra
Product Name: ofatumumab
Product Code: ofatumumab
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: ofatumumab
Current Sponsor code: GSK1841157
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Trade Name: MabThera
Product Name: MabThera
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CAS Number: 174722-31-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Primary Outcome(s)

Main Objective: 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.

Secondary Objective: •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.

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

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.

Secondary Outcome(s)

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.

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.

Secondary ID(s)

2010-018780-42-SK

OMB113676

Source(s) of Monetary Support

GlaxoSmithKline Research and Development Limited