An open-labeled, randomized, two-dose, parallel group trial of ofatumumab, a fully human monoclonal anti-CD20 antibody, in combination with CHOP, in patients with previously untreated Follicular Lymphoma - Ofatumumab with cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) in FL patients

Conditions: on-Hodgkin Follicular Lymphoma
MedDRA version: 17.0Level: PTClassification code 10003899Term: B-cell lymphomaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Registration Number: EUCTR2007-000244-27-SE

Lead Sponsor: GlaxoSmithKline Research and Development Limited

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 56

Inclusion Criteria

1)Patient with Follicular Lymphoma grade 1 – 3, stage III-IV, or Bulky disease stage II (i.e. as any single mass > 5cm in any direction) defined according to WHO guidelines (3)
2)Tumor verified to be CD20+ positive from current or previous excisional or incisional lymph node biopsy . The excisional or incisional lymph node biopsy has to be redone if: no tissue is available for central review or if there is clinical suspicion that the Follicular Lymphoma has transformed to aggressive lymphoma/higher malignancy grade
3)CT scan in screening phase (based on local evaluation) showing:
-2 or more clearly demarcated lesions with a largest diameter = 1.5 cm, or
-1 clearly demarcated lesion with a largest diameter = 2.0 cm

4)ECOG Performance Status of 0, 1, or 2
5)Age = 18 years
6)Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out

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)Any previous treatment for Follicular Lymphoma
2)Clinical suspicion that the Follicular Lymphoma has transformed to aggressive lymphoma (e.g. B symptoms, fast growing tumor or increasing lactate Dehydrogenase (LDH) level) unless new biopsy of clinically suspicious area confirms FL
3)Known CNS involvement of FL
4)Past or current malignancy, except for:
•Follicular Lymphoma
•Cervical carcinoma Stage 1B or less
•Non-invasive basal cell and squamous cell skin carcinoma
•Malignant melanoma with a complete response of a duration of > 10 years
•Other cancer diagnoses with a complete response of a duration of > 5 years
5)Chronic or ongoing active infectious disease requiring systemic treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active hepatitis
6)Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months from Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extra systoles or minor conduction abnormalities
7)Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral, or psychiatric disease
8)Known HIV positive
9)Positive serology for hepatitis B defined by:
i.Positive test for HBsAg or
ii.Positive test for Anti-HBc and Anti-HBs
Patients that have been vaccinated against hepatitis B (primary and secondary immunization and booster) will not be considered positive.
If a test outcome at any time during the study is positive (and this is not due to a previous vaccination), the patient should be withdrawn from further trial treatment and proceed to Follow-up
10)Screening laboratory values:
•platelets < 50 x 109/L (unless due to FL involvement of the bone marrow)
•neutrophils < 1.0 x 109/L (unless due to FL involvement of the bone marrow)
•creatinine > 1.5 times upper normal limit (unless normal creatinine clearance)
•total bilirubin > 1.5 times upper normal limit (unless due to liver involvement of FL or unless due to liver involvement by FL or secondary to Gilbert’s disease)
•ALT > 2.5 times upper normal limit (unless due to liver involvement of FL)
•alkaline phosphatase > 2.5 times upper normal limit (unless due to liver involvement of FL)

11)Ejection fraction <50% as assessed by MUGA or echocardiography
12)Known or suspected hypersensitivity to components of investigational product
13)Patients who have received treatment with any non-marketed drug substance or experimental therapy within 4 weeks prior to Visit 2
14)Current participation in any other interventional clinical study
15)Patients known or suspected of not being able to comply with a study protocol (e.g. due to alcoholism, drug dependency or psychological disorder)
16)Breast feeding women or women with a positive pregnancy test at Visit 1
17)Women of childbearing potential not willing to use adequate contraception for up to one year after last dose of ofatumumab. Adequate contraception is defined as hormonal birth control or intrauterine device. For patients in the USA the use of a double barrier method is also considered adequate.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To investigate the efficacy in two dose regimens of ofatumumab in combination with CHOP in previously untreated patients with FL.;Secondary Objective: To determine the safety and pharmacokinetic profile of ofatumumab in combination with CHOP.;Primary end point(s): Objective Response Rate as measured from start of treatment until 3 months after last infusion assessed according to the standardized response criteria for non-Hodgkin’s Lymphomas

Secondary Outcome Measures