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-FR
• Date of registration: 07/09/2010
• 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 Follicular Lymphoma Releapsed After Rituximab-Containing Therapy
• Date of first enrolment: 11/07/2013
• 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
• 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

Key inclusion & exclusion criteria

Inclusion criteria:
1. Follicular lymphoma; grades 1, 2 and 3A, defined according to WHO guidelines. FL grade 3B (absence of centrocytes) is not eligible for this study. The histology and CD20 expression on tumor cells must be verified by pathology review of a current or previous lymph node biopsy. A bone marrow biopsy is not sufficient for tissue diagnosis.
2. Rituximab-sensitive FL, defined as a partial or complete response to treatment with rituximab or a rituximab-containing regimen lasting at least 6 months following completion of the last rituximab treatment. (Note: Patients must have received at least 4 infusions of single agent rituximab or at least 3 cycles of a rituximab-containing combination chemotherapy regimen.).
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 at least one clearly demarcated lesion with a largest diameter = 2.0 cm by CT scan imaging.
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.
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
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Previous treatment with ofatumumab.
2. Previous radioimmunotherapy (RIT) within 6 months of randomization. Patients who have received previous RIT 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 of randomization.
4. Previous allogeneic stem cell transplantation.
5. Previous anti-lymphoma monoclonal antibody therapy (excluding rituximab), chemotherapy, glucocorticoid, or other systemic therapy for lymphoma within 3 months of randomization.
6. Current or previous participation in another interventional clinical study within 4 weeks of randomization.
7. Current or previous other malignancy within 2 years of 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.
9. Clinically significant cardiac disease as judged by the investigator including unstable angina, acute myocardial infarction within 6 months of randomization, congestive heart failure, and arrhythmia requiring therapy.
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 109/L (unless due to FL involvement of the bone marrow).
b. Platelets < 50 x 109/L (unless due to FL involvement of the bone marrow).
c. ALT or AST > 2xULN, alkaline phosphatase and bilirubin > 1.5xULN (isolated predominantly indirect hyperbilirubinemia due to Gilbert’s syndrome is acceptable for inclusion)
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 p

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

Health Condition(s) or Problem(s) studied

Indolent B-Cell Non-Hodgkin's Lymphoma

Intervention(s)

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)

Secondary Objective: •To 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 FL that has relapsed after prior rituximab-containing therapy.
•To 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 FL 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 FL 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 FL.

Main Objective: To compare progression-free survival following therapy with single agent ofatumumab versus single agent rituximab in subjects with follicular lymphoma that has relapsed after prior rituximab-containing therapy.

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

Secondary ID(s)

2010-018780-42-SK

OMB113676