Study of a new drug combination for the treatment of Non Hodgkin’s Lymphoma

• Register: EUCTR
• Last refreshed on: 24 September 2018
• Main ID: EUCTR2008-004177-17-DE
• Date of registration: 09/03/2010
• Prospective Registration: Yes
• Primary sponsor: Novartis Pharma Services AG
• Public title: Study of a new drug combination for the treatment of Non Hodgkin’s Lymphoma
• 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 - COMPLEMENT A+B
• Date of first enrolment: 08/06/2010
• Target sample size: 346
• 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; 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

Argentina, Austria, Belgium, Brazil, Canada, France, Germany, Greece, Hong Kong, Italy, Japan, Poland, Russian Federation, Slovakia, Ukraine, United Kingdom, United States

Contacts

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma Services AG

• Name: Clinical Trial Information Desk
• Affiliation: Novartis Pharma Services AG

Key inclusion & exclusion criteria

Inclusion criteria:
Subjects eligible for enrollment in the study must meet all of the following criteria:
1. Small lymphocytic lymphoma (SLL), lymphoplasmacytic lymphoma, marginal zone lymphoma, and follicular lymphoma; grades 1, 2 and 3A, defined according to World Health Organization guidelines. Subjects with a diagnosis of SLL who have a peripheral blood monoclonal B lymphocyte count of =5,000/µL are considered to have CLL and are not eligible for this study.
• Tumor verified to be CD20+ positive from a previous or current tissue biopsy.
•CT imaging in screening phase (based on local evaluation) showing 2 or more clearly demarcated lesions/nodes with a long axis >1.5 cm and short axis = 1.0 cm or 1 clearly demarcated lesion/node with a long axis >2.0 cm and short axis =1.0 cm (Section 6.2.5 of Study Protocol). CT imaging performed at screening as baseline image.
2. Indolent B-cell NHL with failure to achieve at least a partial response lasting 6 months beyond the end of treatment with rituximab or a rituximab-containing regimen (See Section 6.2.5.4– Section 6.2.5.5 of study protocol for details on response criteria), i.e.:
•Stable disease (SD) after rituximab or a rituximab-containing regimen (imaging will support this finding. NOTE: in cases of SD after rituximab monotherapy as induction treatment, the minimum time to confirm SD by imaging is 60 days from start of first rituximab infusion) or,
• Disease progression during or within 6 months of treatment with rituximab or a rituximab-containing regimen. Imaging must support this finding and will be done = 6 months after the last infusion of rituximab. Note: Subjects must have received a minimum of 4 rituximab infusions as monotherapy or 3 infusions as part of rituximab-containing combination regimens
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 137
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 130

Exclusion criteria:
Subjects meeting any of the following criteria will not be enrolled in the study:
1. Grade 3b FL or evidence that the indolent lymphoma has transformed to aggressive lymphoma as verified by biopsy confirmation
2. Previous autologous stem cell transplant in the last 6 months or previous allogeneic stem cell transplant at any time.
3. High dose steroids = 25 mg prednisolone/day (or equivalent) for 7 consecutive days, given as concomitant medication, within 3 months prior to randomization. No more than 10 mg prednisone daily at the time of randomization
4. Prior bendamustine treatment within 1 year of randomization not resulting in a CR or PR for at least 6 months
5. Prior use of any monoclonal antibody (other than anti-CD20) within 3 months prior to randomization
6. Known central nervous system (CNS) involvement by indolent lymphoma
7. 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*
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, and active Hepatitis C
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. History of significant cerebrovascular disease or event with significant symptoms or sequelae
11. Significant concurrent, uncontrolled medical condition that in the opinion of the investigator or GSK medical monitor contraindicates participation this study
12. Positive serology for Hepatitis B (HB) defined as a positive test for Hepatitis B surface antigen (HbsAg). In addition, if negative for HBsAg but Hepatits B core antibody (HBcAb) positive (regardless of HBsAb status), a HBV DNA test will be performed and if positive the subject will be excluded
? Consult with a physician experienced in care and management of subjects with Hepatitis B to manage/treat subjects who are anti-HBc positive
? If HBV DNA is negative, subject may be included but must undergo HBV DNA monitoring (see Section 6.5.7.1 of study protocol). Prophylactic antiviral therapy may be initiated at the discretion of the investigator
13. Current active liver or biliary disease (subjects with Gilbert’s syndrome or asymptomatic gallstones, liver metastases related to indolent NHL or otherwise stable chronic liver disease per investigator assessment, are eligible)
14. Known human immunodeficiency virus (HIV) positive
15. Screening laboratory values:
? platelets < 100 x 109/L (unless due to indolent lymphoma involvement of the bone marrow)
? neutrophils < 1.5 x 109/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] or creatinine clearance from a 24- hour urine collection is ? 40 mL/min
? Total bilirubin > 1.5 times ULN (unless due to liver involvement by FL or Gilbert’s disease)
? Transaminases > 3 times ULN
16. Known or suspected hypersensitivity to ofatumumab, bendamustine, or mannitol
17. Treatment with any known non-marketed d

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

Health Condition(s) or Problem(s) studied

Indolent B-cell Non-Hodgkin’s Lymphoma
MedDRA version: 20.0 Level: HLGT Classification code 10025320 Term: Lymphomas non-Hodgkin's B-cell System Organ Class: 10005329 - Blood and lymphatic system disorders

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
CAS Number: 679818-59-8
Current Sponsor code: GSK1841157
Other descriptive name: HuMax-CD20
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 100-

Product Name: Bendamustine
Pharmaceutical Form: Powder for solution for infusion
INN or Proposed INN: Bendamustine
CAS Number: 16506-27-7
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: Please refer to the complete list of timings that can be found in Appendices 1-3 of the study protocol.

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

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

Secondary Objective: · To establish effectiveness of ofatumumab in combination with bendamustine in subjects with follicular lymphoma refractory to rituximab-containing therapy
· To evaluate and compare ORR, OS, time toand duration of response, and time to progression (TTP) in subjects treated with ofatumumab and bendamustine combination therapy to those treated with bendamustine alone
· To evaluate and compare ORR, OS, time to and duration of response, and time to progression (TTP) in subjects with follicular lymphoma treated with ofatumumab and bendamustine combination therapy to those treated with bendamustine alone
· To evaluate and compare the safety and tolerability in subjects treated with ofatumumab and bendamustine combination therapy to those treated with bendamustine alone
· To evaluate and compare the two treatment arms with respect to changes in subjects’ health-related quality of life

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: Please refer to the complete list of timings that can be found in Appendices 1-3 of the study protocol.

Secondary end point(s): Clinical
· Overall response rate (ORR) in all patients and patients with follicular lymphoma
· Overall survival (OS) in all patients and patients with follicular lymphoma
· Time to response and duration of response in all patients and patients with follicular lymphoma
· Time to progression and time to next therapy in all patients and patients with follicular lymphoma
· Changes in health-related quality of life (HRQL) measures in all patients and patients with follicular lymphoma
· Reduction in tumor size
· Improvement in Eastern Cooperative Oncology Group (ECOG) Performance status
· Incidence and severity of AEs, serious adverse events (SAEs) and other safety parameters including frequency of transfusions, development of Human Anti-Human Antibodies (HAHA), incidence of 3 and 4 infections, and myelosuppression (anemia, neutropenia, and thrombocytopenia)
· Overall response rate (ORR) to ofatumumab monotherapy in subjects in Arm B who progress during or following single-agent bendamustine
· Changes in clinical laboratory values
· Quantitative assessments of immunoglobulins G, A and M (IgG, IgA, IgM)
· Plasma ofatumumab concentrations
· B-cell monitoring (CD19+, CD20+)

Secondary ID(s)

2008-004177-17-BE

OMB110918

Source(s) of Monetary Support

Novartis Pharma Services AG