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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01073163




Registration number
NCT01073163
Ethics application status
Date submitted
19/02/2010
Date registered
23/02/2010
Date last updated
24/04/2014

Titles & IDs
Public title
Study to Assess the Effect of Treatment With Bendamustine in Combination With Rituximab on QT Interval in Patients With Advanced Indolent Non-Hodgkin's Lymphoma (NHL) or Mantle Cell Lymphoma (MCL)
Scientific title
A Study to Assess the Effect of Treatment With Bendamustine in Combination With Rituximab on QT Interval in Patients With Advanced Indolent Non-Hodgkin's Lymphoma (NHL) or Mantle Cell Lymphoma (MCL)
Secondary ID [1] 0 0
C18083/3070
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Hodgkin's Lymphoma 0 0
Mantle Cell Lymphoma 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
Treatment: Drugs - Rituximab

Experimental: Bendamustine with Rituximab - Participants were administered bendamustine intravenous (IV) infusion at 90 mg/m\^2 on Days 1 and 2 of each 28-day cycle, and rituximab IV infusion at 375 mg/m\^2 on Day 1 of each 28-day cycle.


Treatment: Drugs: Bendamustine
Bendamustine at 90 mg/m\^2 IV on Days 1 and 2 of a 28-day cycle.

Treatment: Drugs: Rituximab
Rituximab at 375 mg/m\^2 IV on Day 1 of a 28-day cycle.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Mean Change From Baseline in QT Interval as Corrected by the Fridericia Method (QTcF) at End of Infusion
Timepoint [1] 0 0
Baseline ECGs (Day 2 of Cycle 1): 15 minutes prior to bendamustine infusion. Postinfusion ECGs (Day 2 of Cycle 1): at the end of the 30-minute infusion.
Secondary outcome [1] 0 0
Mean Change From Baseline in QTcF at 1 Hour Postinfusion
Timepoint [1] 0 0
Baseline ECGs (Day 2 of Cycle 1): 15 minutes prior to bendamustine infusion. Postinfusion ECGs (Day 2 of Cycle 1): 1 hour postinfusion.
Secondary outcome [2] 0 0
Number of Participants With QTcF New Outlier Events at End of Infusion and 1 Hour Postinfusion
Timepoint [2] 0 0
Baseline ECGs (Day 2 of Cycle 1): 15 minutes prior to bendamustine infusion. Postinfusion ECGs (Day 2 of Cycle 1): at the end of the 30-minute infusion and 1 hour postinfusion.
Secondary outcome [3] 0 0
Number of Participants With New Onset ECG Waveform Morphological Changes
Timepoint [3] 0 0
Baseline ECGs (Day 2 of Cycle 1): 15 minutes prior to bendamustine infusion. Postinfusion ECGs (Day 2 of Cycle 1): at the end of the 30-minute infusion and 1 hour postinfusion.
Secondary outcome [4] 0 0
Number of Participants With Treatment-Emergent Cardiac Disorders
Timepoint [4] 0 0
Adverse events were collected throughout the study and up to 30 days after the last dose of study drug. The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days.
Secondary outcome [5] 0 0
Change From Baseline in QTcF at Maximum Concentration (Cmax) of Bendamustine and Its Metabolites (M3 and M4)
Timepoint [5] 0 0
Baseline ECGs (Day 2 of Cycle 1): 15 minutes prior to bendamustine infusion. Postinfusion ECGs (Day 2 of Cycle 1): at the end of the 30-minute infusion and 1 hour postinfusion.
Secondary outcome [6] 0 0
Model-predicted Bayesian Bendamustine Clearance in the Presence of Rituximab
Timepoint [6] 0 0
Day 1 of Cycle 1: prior to start of bendamustine infusion, immediately postinfusion, 15 minutes and 30 minutes postinfusion. Day 2 of Cycle 1: 15 minutes prior to start of bendamustine infusion, 15 minutes, 30 minutes, 1, 3, and 5 hours postinfusion.
Secondary outcome [7] 0 0
Rituximab Concentrations at 0.5 Hours, 24 Hours, and 7 Days Postinfusion
Timepoint [7] 0 0
Day 1 of Cycle 1: prior to start of rituximab infusion, immediately postinfusion. Day 2 of Cycle 1: 15 minutes prior to the start of the bendamustine infusion. Day 7 and Day 14: anytime. Day 1 of Cycle 2: prior to start of rituximab infusion.
Secondary outcome [8] 0 0
Percentage of Participants With Complete Response (CR)
Timepoint [8] 0 0
The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days.
Secondary outcome [9] 0 0
Percentage of Participants With Overall Response
Timepoint [9] 0 0
The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days.
Secondary outcome [10] 0 0
Overview of Adverse Events
Timepoint [10] 0 0
Adverse events were collected throughout the study and up to 30 days after the last dose of study drug. The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days.
Secondary outcome [11] 0 0
Eastern Cooperative Oncology Group (ECOG) Performance Status at Endpoint
Timepoint [11] 0 0
End of study. The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days.
Secondary outcome [12] 0 0
Worst Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 Grades for Hematology Laboratory Tests Results Overall
Timepoint [12] 0 0
Adverse events were collected throughout the study and up to 30 days after the last dose of study drug. The median number of 28-day cycles was 6.0. The median duration of the treatment period was 143 days.

Eligibility
Key inclusion criteria
Key

* Histopathologic confirmation of one of the following CD20+ B-cell non-Hodgkin's lymphomas. Tissue diagnostic procedures must be performed within 6 months of study entry and with biopsy material available for review:

* follicular lymphoma (grade 1 or 2)
* immunoplasmacytoma/immunocytoma (Waldenstrom's macroglobulinemia)
* splenic marginal zone B-cell lymphoma
* extra-nodal marginal zone lymphoma of mucosa associated lymphoid tumor (MALT) type
* nodal marginal zone B-cell lymphoma
* mantle cell lymphoma
* Meets one of the following need-for-treatment criteria (with the exception of mantle cell lymphoma for which treatment is indicated):

* presence of at least one of the following B-symptoms:

1. fever (>38ºC) of unclear etiology
2. night sweats
3. weight loss of greater than 10% within the prior 6 months
* large tumor mass (bulky disease)
* presence of lymphoma-related complications, including narrowing of ureters or bile ducts, tumor-related compression of a vital organ, lymphoma induced pain, cytopenias related to lymphoma/leukemia, splenomegaly, pleural effusions, or ascites
* hyperviscosity syndrome due to monoclonal gammopathy
* CD20-positive B cells in lymph node biopsy or other lymphoma pathology specimen
* No prior treatment. Patients on "watch and wait" may enter the study if a recent biopsy (obtained within the last 6 months) is available.
* Adequate hematologic function (unless abnormalities related to lymphoma infiltration of the bone marrow or hypersplenism due to lymphoma) as follows:

* hemoglobin of >= 10.0 g/dL
* absolute neutrophil count (ANC) >=1.5*10^9/L
* platelet count >=100*10^9/L
* Bidimensionally measurable disease (field not previously radiated)
* Able to provide written informed consent
* Eastern Cooperative Oncology Group (ECOG) performance status <=2
* Estimated life expectancy >=6 months
* Serum creatinine of <=2.0 mg/dL or creatinine clearance >=50 mL/min
* Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =2.5* upper limit of normal (ULN), and alkaline phosphatase and total bilirubin within normal limits
* Left ventricular ejection fraction (LVEF) >=50% by multiple gated acquisition scan (MUGA) or cardiac echocardiogram (ECHO), prior for any patient to be treated with rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP)
* A medically accepted method of contraception to be used by women of childbearing potential (not surgically sterile or at least 12 months naturally postmenopausal)
* Men capable of producing offspring and not surgically sterile must practice abstinence or use a barrier method of birth control

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Chronic lymphocytic leukemia, small lymphocytic lymphoma (SLL), or grade 3 follicular lymphoma
* Transformed disease. Bone marrow blasts are permitted, however, transformed disease indicating leukemic involvement is not permitted
* Central nervous system (CNS) lymphomatous involvement or leptomeningeal lymphoma
* Prior radiation for non-Hodgkin's lymphoma (NHL), except for a single course of locally delimited radiation therapy with a radiation field not exceeding 2 adjacent lymph node regions
* Active malignancy, other than NHL, within the past 3 years except for localized prostate cancer treated with hormone therapy, cervical carcinoma in situ, breast cancer in situ, or non-melanoma skin cancer following definitive treatment
* New York Heart Association (NYHA) Class III or IV heart failure, arrhythmias or unstable angina, electrocardiographic evidence of active ischemia or active conduction system abnormalities, or myocardial infarction within the last 6 months. (Prior to study entry, ECG abnormalities at screening must be documented by the investigator as not medically relevant)
* Known human immunodeficiency virus (HIV) positivity
* Active hepatitis B or hepatitis C infection (Hepatitis B surface antigen testing required)
* Women who are pregnant or lactating
* Corticosteroids for treatment of lymphoma within 28 days of study entry. Chronically administered low-dose corticosteroids (e.g., prednisone =20 mg/day) for indications other than lymphoma or lymphoma-related complications are permitted
* Any serious uncontrolled, medical or psychological disorder that would impair the ability of the patient to receive therapy
* Any condition which places the patient at unacceptable risk or confounds the ability of the investigators to interpret study data
* Any other investigational agent within 28 days of study entry
* Known hypersensitivity to bendamustine, mannitol, or other study-related drugs
* The patient has Ann Arbor stage I disease
* The patient has a history of congenital long QT syndrome
* The patient has a history of cardiac disease with significant potential for QT prolongation
* The patient has screening electrocardiography (ECG) on Day 1 of Cycle 1 with QTcF interval >450 ms that is confirmed by a second ECG. If the QTcF interval is >450 ms on both ECGs, the ECGs will be sent to eResearch Technology, Inc. (ERT), the Central ECG Reader vendor, for an overread (with 24-hour turn around time) and ERT will make a final decision on enrollment
* The patient has serum potassium or magnesium less than the lower limit of normal

Study design
Purpose of the study
Treatment
Allocation to intervention
Not applicable
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
Single group
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/02/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/06/2012
Sample size
Target
Accrual to date
Final
54
Recruitment in Australia
Recruitment state(s)
ACT,SA,TAS,VIC
Recruitment hospital [1] 0 0
The Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [3] 0 0
The Queen Elizabeth Hospital - Woodville
Recruitment hospital [4] 0 0
Royal Hobart Hospital - Hobart
Recruitment hospital [5] 0 0
The Alfred Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Garran
Recruitment postcode(s) [2] 0 0
- Adelaide
Recruitment postcode(s) [3] 0 0
- Woodville
Recruitment postcode(s) [4] 0 0
- Hobart
Recruitment postcode(s) [5] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
Arkansas
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
Florida
Country [7] 0 0
United States of America
State/province [7] 0 0
Georgia
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Iowa
Country [10] 0 0
United States of America
State/province [10] 0 0
Kansas
Country [11] 0 0
United States of America
State/province [11] 0 0
Kentucky
Country [12] 0 0
United States of America
State/province [12] 0 0
Louisiana
Country [13] 0 0
United States of America
State/province [13] 0 0
Maine
Country [14] 0 0
United States of America
State/province [14] 0 0
Missouri
Country [15] 0 0
United States of America
State/province [15] 0 0
New Mexico
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
Oregon
Country [18] 0 0
United States of America
State/province [18] 0 0
Pennsylvania
Country [19] 0 0
United States of America
State/province [19] 0 0
South Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Tennessee
Country [21] 0 0
United States of America
State/province [21] 0 0
Texas
Country [22] 0 0
United States of America
State/province [22] 0 0
Virginia
Country [23] 0 0
United States of America
State/province [23] 0 0
Washington
Country [24] 0 0
United States of America
State/province [24] 0 0
West Virginia
Country [25] 0 0
Canada
State/province [25] 0 0
Nova Scotia
Country [26] 0 0
Canada
State/province [26] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Cephalon
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Sponsor's Medical Expert
Address 0 0
Cephalon
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

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.

Results are available at https://clinicaltrials.gov/study/NCT01073163