Clincosm LogoSign in Get a demo

BENDACT: Bendamustine Hydrochloride (HCl) in Indolent Non-Hodgkin's Lymphoma That Has Progressed During or Following Treatment With a Rituximab Regimen or Previously Untreated Chronic Lymphocytic Leukemia

Sponsor
Lundbeck Canada Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT01500083
Collaborator
(none)
90
Enrollment
16
Locations
2
Arms
15
Duration (Months)
5.6
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the current study is to evaluate additional safety data of bendamustine in up to 100 patients with Indolent Non-Hodgkin's Lymphoma (iNHL) relapsing from a rituximab regimen or Chronic Lymphocytic Leukemia (CLL). Patients will receive up to 6 or 8 cycles of bendamustine treatment using the dosing regimens of TREANDA® (bendamustine) approved in several countries, which have been shown to be reasonably well tolerated. The study protocol includes safety monitoring (i.e., adverse events, concomitant medications, supportive care, clinical safety laboratory tests, and clinical disease status monitoring).

It is an interventional, multicentre, prospective, open-label expanded access study, which in addition allows investigators in Canada, and their patients, access to bendamustine while it is pending Canadian marketing approval.

Although the treatment options available for patients with iNHL or CLL do induce substantial responses, there is no curative treatment. One potential drug candidate for the treatment of CLL and iNHL is bendamustine.

Bendamustine has been widely used in Germany for more than 30 years and is marketed in the United States for treatment of CLL and for treatment of iNHL that has progressed during or within 6 months of treatment with rituximab or a rituximab-containing regimen. In October 2010, the European Medicines Agency formally approved bendamustine in a number of Member States of the European Union for the treatment of patients with iNHL, CLL, and multiple myeloma. The drug's safety profile in these patient populations has been extensively characterized and no unexpected safety concerns are anticipated.

Condition or Disease Intervention/Treatment Phase
  • Drug: Bendamustine at a dose of 100 mg/m2
  • Drug: Bendamustine at a dose of 120 mg/m2
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
90 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label Expanded Access Trial for Bendamustine HCl in Patients With Indolent Non-Hodgkin's Lymphoma That Has Progressed During or Following Treatment With a Rituximab Regimen or Previously Untreated Chronic Lymphocytic Leukemia
Study Start Date :
Mar 1, 2012
Actual Primary Completion Date :
Jun 1, 2013
Actual Study Completion Date :
Jun 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: Patients with Chronic Lymphocytic Leukemia (CLL)

Patients with CLL will receive bendamustine at a dose of 100 mg/m2 on Days 1 and 2 in treatment cycles of 28 days for up to six cycles.

Drug: Bendamustine at a dose of 100 mg/m2
Bendamustine will be administered intravenously over 30 minutes.
Other Names:
  • Treanda®

    		•
    Experimental: Patients with Indolent Non-Hodgkin's Lymphoma (iNHL)

    Patients with iNHL will receive bendamustine at a dose of 120 mg/m2 on Days 1 and 2 in treatment cycles of 21 or 28 days for up to eight cycles.

    Drug: Bendamustine at a dose of 120 mg/m2
    Bendamustine will be administered intravenous (i.v.) over 60 minutes.
    Other Names:
  • Treanda®

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Adverse Events [Up to 266 days]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria for iNHL:

    • The patient has biopsy-confirmed diagnosis of indolent B-cell NHL documented as relapsed or refractory iNHL (following rituximab-based therapy).

    • The patient has one of the following types of indolent B-cell lymphoma:

    • follicular lymphoma grade 1, 2, or 3A

    • marginal zone lymphoma

    • lymphoplasmacytic lymphoma

    • small lymphocytic lymphoma

    • The patient has adequate haematologic function (unless abnormalities are related to lymphoma involvement of the bone marrow or hypersplenism caused by lymphoma).

    Inclusion Criteria for CLL:

    • The patient has previously confirmed (according to WHO criteria) untreated symptomatic chronic B-cell lymphocytic leukemia Binet Stage B or Binet Stage C or Rai stage II to IV in need of medical treatment.

    • The patient has an Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.

    Exclusion Criteria:

    • The patient has participated in a clinical study <30 days prior to the Screening Visit.

    • The patient has one or more of the following conditions:

    • active transformed lymphoma

    • any history of central nervous system or leptomeningeal lymphoma

    • an active malignancy other than the target cancer within the past 5 years

    • human immunodeficiency virus

    • The patient is, in the investigator's opinion, unlikely to comply with the protocol or is unsuitable for any reason.

    Other inclusion and exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 CA015 Calgary Alberta Canada T2N 4N2
    2 CA014 Edmonton Alberta Canada T6G 1Z2
    3 CA016 Kelowna British Columbia Canada V1Y 5L3
    4 CA011 Vancouver British Columbia Canada V5Z 4E6
    5 CA013 Victoria British Columbia Canada V8R 6V5
    6 CA012 Winnipeg Manitoba Canada R3E 0V9
    7 CA004 Halifax Nova Scotia Canada B3H 2Y9
    8 CA009 Brampton Ontario Canada L6R 3J7
    9 CA003 Hamilton Ontario Canada L8V 5C2
    10 CA002 Ottawa Ontario Canada K1H 8L6
    11 CA006 Toronto Ontario Canada M5G 2M9
    12 CA005 Windsor Ontario Canada N8W 2X3
    13 CA001 Montreal Quebec Canada H2W 1S6
    14 CA010 Montreal Quebec Canada H4J 1C5
    15 CA007 Saskatoon Saskatchewan Canada S7N 4H4
    16 CA008 Quebec Canada G1J 1Z4

    Sponsors and Collaborators

    • Lundbeck Canada Inc.

    Investigators

    • Study Director: Email contact via H. Lundbeck A/S, LundbeckClinicalTrials@lundbeck.com

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Lundbeck Canada Inc.
    ClinicalTrials.gov Identifier:
    NCT01500083
    Other Study ID Numbers:
    • 14293A
    First Posted:
    Dec 26, 2011
    Last Update Posted:
    Aug 14, 2017
    Last Verified:
    Jun 1, 2017
    Keywords provided by Lundbeck Canada Inc.
    iNHL
    CLL
    Additional relevant MeSH terms:
    Lymphoma
    Leukemia
    Lymphoma, Non-Hodgkin
    Leukemia, Lymphoid
    Leukemia, Lymphocytic, Chronic, B-Cell
    Bendamustine Hydrochloride

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Patients With Previously Untreated CLL Patients With iNHL
    Arm/Group Description Patients with CLL will receive bendamustine at a dose of 100 mg/m2 on Days 1 and 2 in treatment cycles of 28 days for up to six cycles. Bendamustine will be administered i.v. over 30 minutes. Patients with iNHL will receive bendamustine at a dose of 120 mg/m2 on Days 1 and 2 in treatment cycles of 21 or 28 days for up to eight cycles. Bendamustine will be administered intravenous (i.v.) over 60 minutes.
    Period Title: Overall Study
    STARTED 16 74
    COMPLETED 4 31
    NOT COMPLETED 12 43

    Baseline Characteristics

    Arm/Group Title Patients With Previously Untreated CLL Patients With iNHL Total
    Arm/Group Description Patients with CLL will receive bendamustine at a dose of 100 mg/m2 on Days 1 and 2 in treatment cycles of 28 days for up to six cycles. Bendamustine will be administered i.v. over 30 minutes. Patients with iNHL will receive bendamustine at a dose of 120 mg/m2 on Days 1 and 2 in treatment cycles of 21 or 28 days for up to eight cycles. Bendamustine will be administered intravenous (i.v.) over 60 minutes. Total of all reporting groups
    Overall Participants 16 74 90
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    69.3
    (7.12)
    63.1
    (10.84)
    64.2
    (10.51)
    Sex: Female, Male (Count of Participants)
    Female
    9
    56.3%
    35
    47.3%
    44
    48.9%
    Male
    7
    43.8%
    39
    52.7%
    46
    51.1%

    Outcome Measures

    1. Primary Outcome
    Title Number of Adverse Events
    Description
    Time Frame Up to 266 days

    Outcome Measure Data

    Analysis Population Description
    APTS
    Arm/Group Title Patients With Previously Untreated CLL Patients With iNHL
    Arm/Group Description Patients with CLL will receive bendamustine at a dose of 100 mg/m2 on Days 1 and 2 in treatment cycles of 28 days for up to six cycles. Bendamustine will be administered i.v. over 30 minutes. Patients with iNHL will receive bendamustine at a dose of 120 mg/m2 on Days 1 and 2 in treatment cycles of 21 or 28 days for up to eight cycles. Bendamustine will be administered intravenous (i.v.) over 60 minutes.
    Measure Participants 16 74
    Number [number of adverse events]
    298
    302

    Adverse Events

    Time Frame Up to 266 days
    Adverse Event Reporting Description
    Arm/Group Title Patients With Previously Untreated CLL Patients With iNHL
    Arm/Group Description Patients with CLL will receive bendamustine at a dose of 100 mg/m2 on Days 1 and 2 in treatment cycles of 28 days for up to six cycles. Bendamustine will be administered i.v. over 30 minutes. Patients with iNHL will receive bendamustine at a dose of 120 mg/m2 on Days 1 and 2 in treatment cycles of 21 or 28 days for up to eight cycles. Bendamustine will be administered intravenous (i.v.) over 60 minutes.
    All Cause Mortality
    Patients With Previously Untreated CLL Patients With iNHL
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Patients With Previously Untreated CLL Patients With iNHL
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 6/16 (37.5%) 27/74 (36.5%)
    Blood and lymphatic system disorders
    Febrile neutropenia 1/16 (6.3%) 4/74 (5.4%)
    Cardiac disorders
    Atrial fibrillation 1/16 (6.3%) 0/74 (0%)
    Cardiac arrest 0/16 (0%) 1/74 (1.4%)
    Gastrointestinal disorders
    Abdominal pain 0/16 (0%) 2/74 (2.7%)
    Diarrhoea 0/16 (0%) 1/74 (1.4%)
    Nausea 0/16 (0%) 2/74 (2.7%)
    Stomatitis 0/16 (0%) 1/74 (1.4%)
    Vomiting 0/16 (0%) 2/74 (2.7%)
    General disorders
    Asthenia 0/16 (0%) 1/74 (1.4%)
    Chills 0/16 (0%) 1/74 (1.4%)
    Multi-organ failure 0/16 (0%) 1/74 (1.4%)
    Pyrexia 3/16 (18.8%) 6/74 (8.1%)
    Systemic inflammatory response syndrome 1/16 (6.3%) 0/74 (0%)
    Immune system disorders
    Hypersensitivity 0/16 (0%) 1/74 (1.4%)
    Infections and infestations
    Bronchopneumonia 1/16 (6.3%) 0/74 (0%)
    Herpes zoster 0/16 (0%) 1/74 (1.4%)
    Neutropenic sepsis 1/16 (6.3%) 0/74 (0%)
    Nocardiosis 0/16 (0%) 1/74 (1.4%)
    Pneumocystis jiroveci pneumonia 0/16 (0%) 2/74 (2.7%)
    Pneumonia 0/16 (0%) 3/74 (4.1%)
    Toxic shock syndrome 0/16 (0%) 1/74 (1.4%)
    Urosepsis 0/16 (0%) 1/74 (1.4%)
    Injury, poisoning and procedural complications
    Infusion related reaction 0/16 (0%) 1/74 (1.4%)
    Transfusion reaction 0/16 (0%) 1/74 (1.4%)
    Metabolism and nutrition disorders
    Hypokalaemia 0/16 (0%) 1/74 (1.4%)
    Tumour lysis syndrome 2/16 (12.5%) 0/74 (0%)
    Nervous system disorders
    Cerebral haemorrhage 0/16 (0%) 1/74 (1.4%)
    Cerebrovascular accident 1/16 (6.3%) 0/74 (0%)
    Peripheral motor neuropathy 0/16 (0%) 1/74 (1.4%)
    Syncope 0/16 (0%) 2/74 (2.7%)
    Renal and urinary disorders
    Renal failure acute 1/16 (6.3%) 2/74 (2.7%)
    Ureteric obstruction 0/16 (0%) 1/74 (1.4%)
    Urinary retention 0/16 (0%) 1/74 (1.4%)
    Respiratory, thoracic and mediastinal disorders
    Interstitial lung disease 0/16 (0%) 1/74 (1.4%)
    Productive cough 1/16 (6.3%) 0/74 (0%)
    Pulmonary embolism 0/16 (0%) 1/74 (1.4%)
    Respiratory failure 0/16 (0%) 1/74 (1.4%)
    Vascular disorders
    Hypotension 1/16 (6.3%) 1/74 (1.4%)
    Other (Not Including Serious) Adverse Events
    Patients With Previously Untreated CLL Patients With iNHL
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 16/16 (100%) 72/74 (97.3%)
    Blood and lymphatic system disorders
    Anaemia 4/16 (25%) 17/74 (23%)
    Febrile neutropenia 1/16 (6.3%) 2/74 (2.7%)
    Haemolysis 1/16 (6.3%) 0/74 (0%)
    Leukocytosis 1/16 (6.3%) 0/74 (0%)
    Lymphadenopathy 1/16 (6.3%) 3/74 (4.1%)
    Neutropenia 5/16 (31.3%) 24/74 (32.4%)
    Thrombocytopenia 5/16 (31.3%) 14/74 (18.9%)
    Cardiac disorders
    Cardiac failure congestive 1/16 (6.3%) 0/74 (0%)
    Sinus tachycardia 1/16 (6.3%) 2/74 (2.7%)
    Tachycardia 1/16 (6.3%) 2/74 (2.7%)
    Ear and labyrinth disorders
    Vertigo 1/16 (6.3%) 2/74 (2.7%)
    Gastrointestinal disorders
    Abdominal distension 1/16 (6.3%) 2/74 (2.7%)
    Abdominal pain 2/16 (12.5%) 2/74 (2.7%)
    Abdominal pain upper 1/16 (6.3%) 3/74 (4.1%)
    Anal pruritus 1/16 (6.3%) 0/74 (0%)
    Constipation 5/16 (31.3%) 23/74 (31.1%)
    Diarrhoea 9/16 (56.3%) 21/74 (28.4%)
    Dry mouth 2/16 (12.5%) 10/74 (13.5%)
    Dyspepsia 1/16 (6.3%) 15/74 (20.3%)
    Dysphagia 1/16 (6.3%) 1/74 (1.4%)
    Flatulence 1/16 (6.3%) 1/74 (1.4%)
    Gastrooesophageal reflux disease 1/16 (6.3%) 2/74 (2.7%)
    Haemorrhoids 0/16 (0%) 4/74 (5.4%)
    Mouth ulceration 1/16 (6.3%) 2/74 (2.7%)
    Nausea 12/16 (75%) 50/74 (67.6%)
    Reflux gastritis 1/16 (6.3%) 1/74 (1.4%)
    Stomatitis 1/16 (6.3%) 7/74 (9.5%)
    Vomiting 9/16 (56.3%) 26/74 (35.1%)
    General disorders
    Asthenia 2/16 (12.5%) 5/74 (6.8%)
    Chest pain 2/16 (12.5%) 4/74 (5.4%)
    Chills 3/16 (18.8%) 11/74 (14.9%)
    Fatigue 8/16 (50%) 43/74 (58.1%)
    Infusion related reaction 1/16 (6.3%) 3/74 (4.1%)
    Injection site phlebitis 1/16 (6.3%) 0/74 (0%)
    Malaise 2/16 (12.5%) 2/74 (2.7%)
    Mucosal inflammation 0/16 (0%) 4/74 (5.4%)
    Oedema peripheral 2/16 (12.5%) 12/74 (16.2%)
    Pain 1/16 (6.3%) 2/74 (2.7%)
    Pyrexia 4/16 (25%) 21/74 (28.4%)
    Infections and infestations
    Cystitis 1/16 (6.3%) 0/74 (0%)
    Eye infection 1/16 (6.3%) 0/74 (0%)
    Herpes virus infection 1/16 (6.3%) 1/74 (1.4%)
    Herpes zoster 0/16 (0%) 6/74 (8.1%)
    Nasopharyngitis 2/16 (12.5%) 1/74 (1.4%)
    Rhinitis 1/16 (6.3%) 0/74 (0%)
    Rhinovirus infection 1/16 (6.3%) 0/74 (0%)
    Sepsis 1/16 (6.3%) 0/74 (0%)
    Skin infection 1/16 (6.3%) 1/74 (1.4%)
    Upper respiratory tract infection 0/16 (0%) 5/74 (6.8%)
    Urinary tract infection 1/16 (6.3%) 2/74 (2.7%)
    Injury, poisoning and procedural complications
    Contusion 1/16 (6.3%) 2/74 (2.7%)
    Excoriation 1/16 (6.3%) 0/74 (0%)
    Investigations
    Blood alkaline phosphatase increased 1/16 (6.3%) 1/74 (1.4%)
    Blood bilirubin increased 1/16 (6.3%) 2/74 (2.7%)
    Blood creatinine increased 2/16 (12.5%) 0/74 (0%)
    Blood lactate dehydrogenase increased 2/16 (12.5%) 1/74 (1.4%)
    Blood magnesium decreased 1/16 (6.3%) 0/74 (0%)
    Blood urea increased 1/16 (6.3%) 1/74 (1.4%)
    Gamma-glutamyltransferase increased 2/16 (12.5%) 1/74 (1.4%)
    Haemoglobin decreased 0/16 (0%) 6/74 (8.1%)
    Haptoglobin decreased 1/16 (6.3%) 0/74 (0%)
    Lymphocyte count decreased 2/16 (12.5%) 1/74 (1.4%)
    Neutrophil count decreased 4/16 (25%) 7/74 (9.5%)
    Platelet count decreased 2/16 (12.5%) 11/74 (14.9%)
    Weight decreased 2/16 (12.5%) 9/74 (12.2%)
    White blood cell count decreased 2/16 (12.5%) 6/74 (8.1%)
    Metabolism and nutrition disorders
    Decreased appetite 4/16 (25%) 20/74 (27%)
    Hypercalcaemia 1/16 (6.3%) 3/74 (4.1%)
    Hyperchloraemia 3/16 (18.8%) 0/74 (0%)
    Hyperglycaemia 3/16 (18.8%) 1/74 (1.4%)
    Hyperkalaemia 2/16 (12.5%) 1/74 (1.4%)
    Hyperuricaemia 1/16 (6.3%) 1/74 (1.4%)
    Hypokalaemia 2/16 (12.5%) 6/74 (8.1%)
    Hypomagnesaemia 3/16 (18.8%) 5/74 (6.8%)
    Hyponatraemia 1/16 (6.3%) 0/74 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/16 (6.3%) 7/74 (9.5%)
    Back pain 2/16 (12.5%) 7/74 (9.5%)
    Flank pain 1/16 (6.3%) 0/74 (0%)
    Joint swelling 1/16 (6.3%) 2/74 (2.7%)
    Muscle atrophy 1/16 (6.3%) 0/74 (0%)
    Muscle spasms 1/16 (6.3%) 4/74 (5.4%)
    Musculoskeletal pain 2/16 (12.5%) 1/74 (1.4%)
    Myalgia 2/16 (12.5%) 6/74 (8.1%)
    Neck pain 1/16 (6.3%) 2/74 (2.7%)
    Pain in extremity 0/16 (0%) 4/74 (5.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Meningioma 1/16 (6.3%) 0/74 (0%)
    Nervous system disorders
    Ageusia 1/16 (6.3%) 0/74 (0%)
    Amnesia 1/16 (6.3%) 2/74 (2.7%)
    Disturbance in attention 1/16 (6.3%) 3/74 (4.1%)
    Dizziness 2/16 (12.5%) 13/74 (17.6%)
    Dysgeusia 0/16 (0%) 17/74 (23%)
    Headache 5/16 (31.3%) 17/74 (23%)
    Psychiatric disorders
    Anxiety 2/16 (12.5%) 4/74 (5.4%)
    Insomnia 0/16 (0%) 6/74 (8.1%)
    Renal and urinary disorders
    Dysuria 1/16 (6.3%) 1/74 (1.4%)
    Micturition urgency 1/16 (6.3%) 1/74 (1.4%)
    Pollakiuria 0/16 (0%) 5/74 (6.8%)
    Respiratory, thoracic and mediastinal disorders
    Cough 3/16 (18.8%) 13/74 (17.6%)
    Dyspnoea 3/16 (18.8%) 9/74 (12.2%)
    Epistaxis 1/16 (6.3%) 0/74 (0%)
    Haemoptysis 1/16 (6.3%) 0/74 (0%)
    Hypoxia 1/16 (6.3%) 1/74 (1.4%)
    Nasal congestion 0/16 (0%) 4/74 (5.4%)
    Oropharyngeal pain 2/16 (12.5%) 8/74 (10.8%)
    Pleural effusion 1/16 (6.3%) 1/74 (1.4%)
    Skin and subcutaneous tissue disorders
    Dermatitis exfoliative 1/16 (6.3%) 0/74 (0%)
    Dry skin 1/16 (6.3%) 2/74 (2.7%)
    Erythema 1/16 (6.3%) 5/74 (6.8%)
    Hyperhidrosis 1/16 (6.3%) 1/74 (1.4%)
    Night sweats 0/16 (0%) 4/74 (5.4%)
    Pruritus 1/16 (6.3%) 7/74 (9.5%)
    Rash 2/16 (12.5%) 8/74 (10.8%)
    Rash generalised 1/16 (6.3%) 0/74 (0%)
    Rash maculo-papular 2/16 (12.5%) 1/74 (1.4%)
    Rash papular 2/16 (12.5%) 0/74 (0%)
    Vascular disorders
    Hot flush 1/16 (6.3%) 1/74 (1.4%)
    Hypertension 1/16 (6.3%) 1/74 (1.4%)
    Hypotension 1/16 (6.3%) 4/74 (5.4%)
    Phlebitis 0/16 (0%) 5/74 (6.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The results of this study will be published. Authors of the primary publication based on this study must fulfil the criteria defined by the International Committee of Medical Journal Editors (ICMJE). The primary publication must be published before any secondary publications are submitted for publication.

    Results Point of Contact

    Name/Title Lundbeck Canada Inc.
    Organization Lundbeck Canada Inc.
    Phone +45 36301311
    Email LundbeckClinicalTrials@lundbeck.com
    Responsible Party:
    Lundbeck Canada Inc.
    ClinicalTrials.gov Identifier:
    NCT01500083
    Other Study ID Numbers:
    • 14293A
    First Posted:
    Dec 26, 2011
    Last Update Posted:
    Aug 14, 2017
    Last Verified:
    Jun 1, 2017