A Trial to Investigate the Efficacy of Bendamustine in Patients With Indolent Non-Hodgkin's Lymphoma (NHL) Refractory to Rituximab. (ROBIN)

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Mundipharma Research Limited
Sponsor:
Information provided by (Responsible Party):
Mundipharma Research Limited
ClinicalTrials.gov Identifier:
NCT01289223
First received: February 2, 2011
Last updated: October 15, 2014
Last verified: October 2014
  Purpose

To compare the efficacy of bendamustine against treatment of physician's choice on progression-free survival in subjects with indolent B-cell NHL.


Condition Intervention Phase
Indolent B-cell NHL
Drug: Bendamustine IV
Other: Treatment of Physicians Choice
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Mundipharma Research Limited:

Primary Outcome Measures:
  • Progression-free survival [ Time Frame: 8 cycles of 21 days, then follow up every 3 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Response Rate [ Time Frame: 8 cycles of 21 days, then follow up every 3 months until progressive disease, then every 6 months for overall survival ] [ Designated as safety issue: Yes ]
    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


Estimated Enrollment: 125
Study Start Date: February 2011
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Other: 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.
Other Name: Defined as any cancer specific therapy or best supportive care.
Experimental: Bendamustine IV
Up to 8 cycles of Bendamustine (120mg/m2 Days 1 and 2, every 21 days (+ 3 days).
Drug: Bendamustine IV

Detailed Description:

To test whether bendamustine will improve progression-free survival in subjects with indolent B-cell NHL that did not respond (stable disease or progressive disease) to rituximab or a rituximab-containing regimen during or within 6 months of the last rituximab treatment compared to treatment of physican's choice.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01289223

Contacts
Contact: Margaret C Wilson info@contact-clinical-trials.com
Contact: Jill Kiteley info@contact-clinical-trials.com

Locations
Australia, Queensland
Princess Alexandra Hospital Recruiting
Brisbane, Queensland, Australia, QLD 4102
Contact: Peter Wood    +61 7 3240 5559    Peter_Wood@health.qld.gov.au   
Czech Republic
Dr Ludmila Demitrovicova Recruiting
Bratislava, Czech Republic
Sponsors and Collaborators
Mundipharma Research Limited
  More Information

No publications provided

Responsible Party: Mundipharma Research Limited
ClinicalTrials.gov Identifier: NCT01289223     History of Changes
Other Study ID Numbers: BDM3502, 2010-022102-41
Study First Received: February 2, 2011
Last Updated: October 15, 2014
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Slovakia: State Institute for Drug Control
Italy: Instituto Clinico Humanitax (IRCCS)
Portugal: INFARMED
Australia: Department of Health & Ageing

Keywords provided by Mundipharma Research Limited:
Indolent B-cell NHL, bendamustine, rituximab, progression-free survival

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Bendamustine
Nitrogen Mustard Compounds
Rituximab
Alkylating Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antirheumatic Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014