A Randomized, Open Label Study of Ofatumumab and Bendamustine Combination Therapy Compared with Bendamustine Monotherapy in Indolent B-cell Non-Hodgkin’s Lymphoma Unresponsive to Rituximab or a Rituximab-Containing Regimen During or Within Six Months of Treatment

• Register: EUCTR
• Last refreshed on: 28 February 2019
• Main ID: EUCTR2008-004177-17-FR
• Date of registration: 09/03/2010
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Research & Development Limited
• Public title: A Randomized, Open Label Study of Ofatumumab and Bendamustine Combination Therapy Compared with Bendamustine Monotherapy in Indolent B-cell Non-Hodgkin’s Lymphoma Unresponsive to Rituximab or a Rituximab-Containing Regimen During or Within Six Months of Treatment
• Scientific title: A Randomized, Open Label Study of Ofatumumab and Bendamustine Combination Therapy Compared with Bendamustine Monotherapy in Indolent B-cell Non-Hodgkin’s Lymphoma Unresponsive to Rituximab or a Rituximab-Containing Regimen During or Within Six Months of Treatment
• Date of first enrolment: 13/05/2013
• Target sample size: 376
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2008-004177-17
• 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

Austria, Belgium, France, Germany, Greece, Italy, Poland, Slovakia, United Kingdom

Key inclusion & exclusion criteria

Inclusion criteria:
1. Indolent lymphoma including grades 1-3a follicular, small lymphocytic, lymphoplasmacytic, and marginal zone lymphoma; stages III-IV, or bulky disease stage II (i.e. as any single mass > 5 cm in any direction) defined according to WHO guidelines [WHO, 2001]:
• Tumor verified to be CD20+ positive from a previous or current lymph node biopsy
• CT imaging 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. CT imaging performed at screening as baseline image
2. Indolent B-cell NHL that remains stable or unresponsive during or within 6 months of treatment with rituximab or a rituximab-containing regimen (See Section 6.2.4.5):
• Maintaining stable disease or failure to achieve PR to rituximab-based therapy. (CT imaging will support this finding, and will be performed at least 30 days after the last dose of rituximab-based therapy)
or,
• disease progression while on rituximab-based therapy (e.g., includes 4 weekly courses of rituximab given at 6-week intervals [Hainsworth, 2005])
or,
• disease progression in subjects with stable disease or better response to rituximab-based therapy <6 months of the last dose of rituximab
Note: Subjects must have received at least 4 infusions of rituximab (either as monotherapy or in combination with any chemotherapy).
3. ECOG Performance Status of 0, 1, or 2
4. Age = 18 years
5. Life expectancy of at least 6 months
6. Signed written informed consent prior to performing any study-specific procedures
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. Grade 3b follicular lymphoma or evidence that the indolent lymphoma has transformed to aggressive lymphoma as verified by biopsy confirmation [e.g. constitutional symptoms, poor performance status, fast growing tumor or increasing lactate dehydrogenase (LDH) level]

2. Previous allogeneic stem cell transplant

3. Previous autologous stem cell transplant, fludarabine therapy, or radioimmunotherapy in the past 12 months

4. Previous external beam radiation therapy to the pelvis. Previous external beam radiation therapy for bony disease to the cranium, mediastinum, and axilla or to more than 3 vertebral bodies

5. High dose steroids = 60 mg prednisone/day (or equivalent) within 3 months of randomization. No more than 10 mg prednisone daily at the time of randomization

6. Prior bendamustine treatment within 1 year of randomization not resulting in a CR or PR for at least 6 months

7. Treatment with anti-CD20 monoclonal antibody within 3 months of randomization

8. Known CNS involvement of indolent lymphoma

9. Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of definitively treated non-melanoma skin cancer, or successfully treated in situ carcinoma, are eligible*

10. 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, and active Hepatitis C

11. Clinically significant cardiac disease including unstable angina, acute myocardial infarction within 6 months from Visit 1, congestive heart failure, and arrhythmia requiring therapy, with the exception of extrasystoles or minor conduction abnormalities

12. History of significant cerebrovascular disease or event with significant symptoms or sequelae

13. Significant concurrent, uncontrolled medical condition that in the opinion of the investigator or GSK medical Monitor contraindicates participation this study

14. 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**

15. Current active liver or biliary disease (with the exception of Gilbert’s syndrome or asymptomatic gallstones, liver metastases or otherwise stable chronic liver disease per investigator assessment)

16. Known HIV positive

17. Screening laboratory values:
• platelets < 100 x 10^9/L (unless due to indolent lymphoma involvement of the bone marrow)
• neutrophils < 1.5 x 10^9/L (unless due to indolent lymphoma involvement of the bone marrow)
• Serum creatinine > 1.5 times the institution’s upper limit of normal (ULN); subjects with a serum creatinine > 1.5 ULN will be eligible if the calculated creatinine clearance [Cockcroft, 1976] from a 24-hour urine collection is > or = 40 mL/min.
• Total bilirubin > 1.5 times ULN (unless due to liver involvement by FL or Gilbert’s disease)
• Transaminases > 3 times ULN.

18. Previous treatment or known or sus

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: 100-

Trade Name: Ribomustin
Product Name: Bendamustine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Bendamustine
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Main Objective: • To establish effectiveness of ofatumumab in combination with bendamustine in patients with indolent B-cell NHL disease relapsed after rituximab therapy

Primary end point(s): • Progression-free survival, defined as the time interval between randomization and disease progression or death

Secondary Objective: • To establish overall response rate, overall survival, time to and duration of response, and time to progression in subjects treated with ofatumumab (O) and bendamustine (B) combination therapy to those treated with bendamustine monotherapy
• To evaluate and compare the safety and tolerability in subjects treated with O and B combination therapy to those treated with B alone
• To evaluate ofatumumab pharmacokinetics when given with bendamustine
• To evaluate and compare the two treatment arms with respect to changes in subjects’ health-related quality of life
• To evaluate and compare prognostic markers and their correlation with clinical responses in subjects treated with O and B compared to those treated with B monotherapy (i.e. ALC, FcR gamma 3)
• To evaluate the overall response rate to optional O monotherapy in subjects who are unresponsive to rituximab during or within 6 months of a rituximab-containing regimen who progress during or following single-agent bendamustine

Secondary ID(s)

2008-004177-17-BE

OMB110918

Ethics review

Status: Approved
Approval date:
Contact: