indolent B-cell Non-Hodgkin's Lymphoma (NHL) that is refractory to rituximab MedDRA version: 12.1 Level: LLT Classification code 10029601 Term: Non-Hodgkin's lymphoma refractory
Conditions
Interventions
Trade Name: Levact
Product Name: Bendamustine
Pharmaceutical Form: Powder for concentrate for solution for infusion
INN or Proposed INN: Bendamustine Hydrochloride
CAS Number: 3543757
Concentration u
Sponsors
Mundipharma Research Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Indolent B-cell lymphoma: 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 Classification, 2008 (see Appendix 12.1. for WHO Classification and Appendix 12.2. for staging) 2. CT imaging in the 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 will be considered the baseline image. 3. Indolent B-cell NHL that remains stable or unresponsive during or within 6 months of treatment with rituximab or a rituximab-containing regimen: •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) OR •Disease progression in subjects with stable disease or better response to rituximab based therapy =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 tumour or increasing lactate dehydrogenase [LDH] levels) 2. Previous allogeneic stem cell transplant 3. 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. 4. More than 10 mg prednisone daily at the time of randomisation 5. Prior bendamustine treatment within 1 year of randomisation not resulting in a CR or PR for at least 6 months 6. Known CNS involvement of 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 including unstable angina, acute myocardial infarction within 6 months from screening, congestive heart failure, and arrhythmia requiring therapy, with the exception of extrasystoles or minor conduction abnormalities. Subjects with well controlled congestive heart failure and atrial arrhythmias need not be excluded but should be discussed with the study Medical Monitor. 10. Significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, haematological, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease 11. History of significant cerebrovascular disease or event with significant symptoms or sequelae 12. 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) 13. Jaundice 14. Known HIV, Hepatitis B, or Hepatitis C positive 15. Creatinine clearance = 10 mL/min (measured or estimated using Cockcroft and Gault equation [Cockcroft, 1976]) 16. Treatment with any known non-marketed drug substance or experimental therapy within 5-terminal half-lives or 4 weeks prior to screening, whichever is longer, or currently participating in any other interventional clinical study unless the sole purpose of the study is for collection of survival data 17. Known or suspected inability to comply with the study protocol 18. Lactating women, women with a positive pregnancy test at screening or women (of childbearing potential) as well as men with partners of childbearing potential, who are not willing to use adequate contraception from study start through last treatment dose and for 6 months following cessation of treatment. Female contraception must be individually recommended by an expert. Adequate contraception is defined as abstinence, oral contraceptive, either combined or progestogen alone, injectable progestogen, implants of levonorgestrel, estrogenic vaginal ring, percutaneous contraceptive patches, intrauterine device (IUD) or intrauterine system (IUS), male partner sterilisation (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for t
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to compare the efficacy of bendamustine against treatment of physician's choice (TPC) on progression-free survival (PFS) in subjects with indolent B-cell NHL that did not respond (stable disease [SD] or progressive disease [PD]) to rituximab or a rituximab containing regimen during or within 6 months of the previous rituximab treatment;Secondary Objective: To compare the following measures in those subjects receiving bendamustine to those subjects receiving reatmentof Physician’s Choice (TPC): •Overall Response Rate (ORR) (Complete remission [CR]/partial remission [PR]) •Duration of response •Overall survival (OS) •Safety and tolerability •Change in health related quality of life (HRQL) measures ;Primary end point(s): Primary endpoints: - PFS - defined as the interval between randomisation and disease progression or death Secondary endpoints: - Overall response rate. Responders will include subjects with CR/PR. Non responders will be those subjects with SD or PD - Duration of response - defined as time from initial response (CR/PR) to progression or death - Overall survival - defined as time from randomisation to death - Safety and tolerability - Change in HRQL measures | — |
Countries
Italy, Poland, Portugal, Slovakia, Spain
Outcome results
None listed