The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT01289223




Registration number
NCT01289223
Ethics application status
Date submitted
2/02/2011
Date registered
3/02/2011
Date last updated
4/09/2018

Titles & IDs
Public title
A Trial to Investigate the Efficacy of Bendamustine in Patients With Indolent Non-Hodgkin's Lymphoma (NHL) Refractory to Rituximab.
Scientific title
A Randomised, Open Label, Multi-centre, Phase III Study to Investigate the Efficacy of Bendamustine Compared to Treatment of Physician's Choice in the Treatment of Subjects With Indolent Non-Hodgkin's Lymphoma (NHL) Refractory to Rituximab
Secondary ID [1] 0 0
2010-022102-41
Secondary ID [2] 0 0
BDM3502
Universal Trial Number (UTN)
Trial acronym
ROBIN
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Indolent B-cell NHL 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Bendamustine IV
Other interventions - Treatment of Physicians Choice

Active Comparator: Treatment of Physicians Choice - Defined as any cancer specific therapy or best supportive care. Treatment should be given according to the label and based upon local institutional medical practice and clinical judgement.

Experimental: Bendamustine IV - Up to 8 cycles of Bendamustine (120mg/m2 Days 1 and 2, every 21 days (+ 3 days).


Treatment: Drugs: Bendamustine IV


Other interventions: Treatment of Physicians Choice
Defined as any cancer specific therapy or best supportive care. Treatment should be given according to the label and based upon local institutional medical practice and clinical judgement.

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free survival - Screening of 14 days, prior to ramdomisation. 8 cycles of 21 days, then follow up every 3 months after end of last cycle until disease progression, then every 6 months.
Timepoint [1] 0 0
8 cycles of 21 days, then follow up every 3 months
Secondary outcome [1] 0 0
Overall Response Rate - Complete remission (CR)/partial remission (PR), Duration of response (DR), Overall survival (OS), Safety and tolerability, Change in health related quality of life (HRQL) measures
Timepoint [1] 0 0
8 cycles of 21 days, then follow up every 3 months until progressive disease, then every 6 months for overall survival

Eligibility
Key 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

2. 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 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 (7 x 109 cells/L)

- Absolute neutrophil count (ANC) = 1,000/µL (1.0 x 109 cells/L)

- ALT, AST and alkaline phosphatase = 2.5 ULN and total bilirubin = 1.5 xULN
(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. Life expectancy of at least 3 months

8. Signed written informed consent prior to performing any study-specific procedures

Main 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)
level]

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 prednisolone 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 of 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)

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 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 sterilization (vasectomy with documentation of azoospermia) prior to the
female subject's entry into the study, and this male is the sole partner for that
subject, or double barrier method: condom and an occlusive cap (diaphragm or
cervical/vault caps) with a vaginal spermicidal agent
(foam/gel/film/cream/suppository).

20.Major surgery less than 30 days prior to start of treatment. 21.Known hypersensitivity
to the active substance or any excipients that cannot be controlled by appropriate
pre-medication
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 0 0
Princess Alexandra Hospital - Brisbane
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
QLD 4102 - Brisbane
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment outside Australia
Country [1] 0 0
Slovakia
State/province [1] 0 0
Bratislava

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Mundipharma Research Limited
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
To compare the efficacy of bendamustine against treatment of physician's choice on
progression-free survival in subjects with indolent B-cell NHL.
Trial website
https://clinicaltrials.gov/show/NCT01289223
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT01289223