A randomised, open label, multi-centre, Phase III study to investigate theefficacy of bendamustine compared to treatment of physician's choice inthe treatment of subjects with indolent Non-Hodgkin's Lymphoma (NHL)refractory to rituximab.
- Conditions
- indolent B-cell Non-Hodgkin's Lymphoma (NHL) that is refractory to rituximabMedDRA version: 12.1Level: LLTClassification code 10029601Term: Non-Hodgkin's lymphoma refractory
- Registration Number
- EUCTR2010-022102-41-SK
- Lead Sponsor
- Mundipharma Research Ltd.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 125
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 <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).
4. Screening laboratory values:
•Platelets = 75,000/µL (75 x 10 9 cells/L)
•Absolute neutrophil count (ANC) = 1,000/µL (1.0 x 10 9 cells/L)
•ALT, AST and alkaline phosphatase = 2.5 x ULN, and total bilirubin = 1.5 x ULN
(isolated predominantly indirect hyperbilirubinaemia due to Gilbert's syndrome is
acceptable for inclusion)
5. ECOG Performance Status of 0, 1, or 2
6. Age = 18 years
7. Estimated life expectancy of at least 3 months
8. Signed written informed consent obtained prior to performing any study-specific
procedures
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
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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method