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Trial registered on ANZCTR


Registration number
ACTRN12618000055202p
Ethics application status
Submitted, not yet approved
Date submitted
5/12/2017
Date registered
17/01/2018
Date last updated
17/01/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
A study of the safety and effectiveness of Lipegfilgrastim, a growth factor, to prevent fever and infections ('febrile neutropenia') in patients undergoing chemotherapy for Non-Hodgkin Lymphoma (NHLL)
Scientific title
LIPEG: A Phase IV, postmarketing
study of the safety and efficacy of Lipegfigrastim (Lonquex ®) as febrile
neutropenia (FN) prophylaxis in patients undergoing chemoimmunotherapy (CIT) for NonHodgkin
Lymphoma
(NHL).
Secondary ID [1] 293539 0
Nil known
Universal Trial Number (UTN)
Trial acronym
LIPEG
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Non-Hodgkin Lymphoma 305740 0
Condition category
Condition code
Cancer 304959 304959 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 304960 304960 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Lipegfilgrastim is currently approved for primary and secondary prophylaxis of febrile neutropenia world-wide, including Australia. However, there is a paucity of data in the haematological setting, including patients undergoing immuno-chemotherapy for NHL.

We wish to undertake a study of the safety and efficacy of lipegfilgrastim in patients with NHL undergoing immuno-chemotherapy.

To assess the efficacy of lipegfilgrastim, the study will assess the rate of febrile neutropenia (FN) in patents receiving chemo-immunotherapy (CIT) for Non-Hodgkin Lymphoma (NHL).
To assess the safety of the lipegfilgrastim,, adverse events (i.e allergic reactions, bony pain, other side effects and tolerability), will be recorded.

Lipegfilgrastim 6mg is administered via subcutaneous injection 24-72 hours post each cycle of chemoimmunotherapy, as per manufacturer's recommendations (based on preclinical and clinical data). The chemoimmunotherapy regimen will depend on the type of lymphoma. For the purposes of this study, lipegfilgrastim will be administered by clinical trial nursing staff.

The frequency and duration of the lipegfilgratim will be variable for each participant ie will depend on the prescribed chemoimmunotherapy regimen (ie this variable is not controlled for this trial).
Intervention code [1] 299775 0
Prevention
Comparator / control treatment
The control group is historical data regarding rates of febrile neutropenia Likelihood of Febrile Neutropenia (FN), and recommendations for growth factor support.

The historical data is based on previous studies of patients undergoing CIT for Non-Hodgkin Lymphoma. These are summarised in the internationally recognised guidelines: (Pettengell, R. et al. Implications of the European Organisation for Research And Treatment Of Cancer (EORTC) guidelines on the use of granulocyte colony-stimulating factor (G-CSF) for lymphoma care. Clin Drug Investig. 29, 491–513 (2009).
Control group
Historical

Outcomes
Primary outcome [1] 304139 0
rate of febrile neutropenia (FN) in patents receiving chemoimmunotherapy (CIT) for Non-Hodgkin Lymphoma (NHL).

Assessment methods:
-Occurrence of febrile neutropenia, defined as an oral temperature >38.2C, or two consecutive readings of >38.0°C for 2 h, and an absolute neutrophil count <0.5 × 109/l, or expected to fall below 0.5 × 109/l
Timepoint [1] 304139 0
Time point: any period since commencement of lipegfilgrastim until completion of chemoimmunotherapy and recovery of neutrophil count.
Secondary outcome [1] 341080 0
To assess rate of neutropenia (neutrophil count <2.0 x 10^9/L) in patients receiving chemo-immunotherapy for Non-Hodgkin Lymphoma and lipegfilgrastim. The degree of neutropenia will also be measured ie.
Grade 1: neutrophil count 1.5-<2.0x10^9/L
Grade 2: neutrophil count <1.5-1X10^9/L
Grade 3: neutrophil count <1.0-0.5X10^9/L
Grade 4: neutrophil count <0.5X1-^9/L
Timepoint [1] 341080 0
Time point: any period since commencement of lipegfilgrastim until completion of chemoimmunotherapy and recovery of neutrophil count.
Secondary outcome [2] 341081 0
Episodes of delay of chemoimmunotherapy (>24 hours)
Timepoint [2] 341081 0
Assessments [review of history] will occur on day one of each trial cycle, reviewing information/data from previous cycle. There will also be an end of study appointment once neutrophil recovery has occurred after last cycle of CIT (approximately 21 days but dependent on CIT regimen).
Secondary outcome [3] 341497 0
safety of lipegfilgrastim. The following outcomes will be recorded:
allergic reactions [from physical examination and history on day 1 of each trial cycle]
injection site reactions [from physical examination and history on day 1 of each trial cycle]
bony pain [from physical examination and history on day 1 of each trial cycle]

this will be a composite secondary outcome.
Timepoint [3] 341497 0
Time point: any period since commencement of lipegfilgrastim until completion of of study period (including 3 month post treatment follow-up appointment).

Assessments [history and physical examination] will occur on day one of each trial cycle until end of cycle, with a follow up 3 months post completion of the trial.
The end of the trial will coincide with the last cycle of planned chemoimmunotherapy. There will also be a follow up appointment 3 months after completion of the trial.
Secondary outcome [4] 341879 0
chemoimmunotherapy dose reductions (<25% of any chemotherapy component)
Timepoint [4] 341879 0
Assessments [review of history] will occur on day one of each trial cycle, reviewing information/data from previous cycle. There will also be an end of study appointment once neutrophil recovery has occurred after last cycle of CIT (approximately 21 days but dependent on CIT regimen).
Secondary outcome [5] 341880 0
chemoimmunotherapy dose reductions (<25% of any chemotherapy component)
Timepoint [5] 341880 0
Assessments [review of history] will occur on day one of each trial cycle, reviewing information/data from previous cycle. There will also be an end of study appointment once neutrophil recovery has occurred after last cycle of CIT (approximately 21 days but dependent on CIT regimen).
Secondary outcome [6] 341881 0
Number of hospital admissions
Timepoint [6] 341881 0
Assessments [review of history] will occur on day one of each trial cycle, reviewing information/data from previous cycle. There will also be an end of study appointment once neutrophil recovery has occurred after last cycle of CIT (approximately 21 days but dependent on CIT regimen).
Secondary outcome [7] 341882 0
Deaths
Timepoint [7] 341882 0
Time point: any period since commencement of lipegfilgrastim until completion of chemoimmunotherapy and 3 months post end of study follow-up appointment.
Secondary outcome [8] 341883 0
overall survival
Timepoint [8] 341883 0
Time point: any period since commencement of lipegfilgrastim until completion of chemoimmunotherapy and 3 months post end of study follow-up appointment.

Eligibility
Key inclusion criteria
• Confirmed diagnosis of NHL (new diagnosis or relapsed/refractory)
• NHL requiring CIT (subject is allowed to have commenced CIT, but must not have received more than 1 cycle)
• Subjects meets EORTC criteria for G-CSF administration:
o Prophylactic: Predicted FN risk >20%, or >10% with at least 1 patients associated risk factors for FN as per the EORTC
o Secondary: previous history of CIT related FN (including Cycle 1 of current CIT)
• Age greater than or equal to 18 years
• Subject must have ability to provide written informed consent before any study-specific procedure is performed
• Subjects receiving salvage CIT are eligible, but will discontinue trial prior to stem cell harvestation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Active infection with Hepatitis B virus or Hepatitis C virus
• Known infection with human immunodeficiency virus (HIV)
• Active infection (patient must be haemodynamically stable and not on any intravenous antibiotics for at least 48 hours)
• Subject is pregnant or breast feeding
• Known sensitivity to lipegfiltrastim or other G-CSF products
• Subject will not be available for follow-up assessment
• Inadequate functional status (ECOG >2)
• Grade >3 pain disorder (as per CTCAE 4.03), including osteoarthritis or other bone/muscular pain disorders

Study design
Purpose of the study
Prevention
Allocation to intervention
Non-randomised 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
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
All analyses will be restricted to the subset of the patients registered on the study who commence chemotherapy and who receive at least one dose of the study drug (lipegfilgrastim). The disposition of all registered patients (inclusion or exclusion from the analysis set) will be reported.
Patient demographics/other baseline characteristics
Demographic and other baseline characteristics including age, gender, height, weight, etc will be summarized using descriptive statistics such as mean, standard deviation, median, 25th and 75th percentiles, minimum and maximum for continuous data or contingency tables presenting frequencies and percentages for categorical data.



For the key secondary endpoint (degree of neutropenia), ordinal logistic regression, accounting for cycles within patients, will also be used to estimate the cumulative probabilities of degrees of neutropenia (using PROC GENMOD in SAS).
Time to death from the date of first dose of lipefilgrastim will be summarized by calculating the Kaplan-Meier estimate of overall survival (OS). The median OS together with its 95% confidence interval (CI) will be reported. Patients who withdraw from the study will have their OS censored at the date of withdrawal. For patients lost to follow-up, OS will be censored at the date of the end-of-treatment assessment, otherwise OS will be censored at the date of the 3-months post therapy “follow-up” assessment.

Sample size
Sample size has been pragmatically determined and 30 patients are expected to be registered on the study in 24 months. With 30 evaluable patients, an expected rate of febrile neutropenia (FN) of no more than 20%, and using the formula for the variance of a binomial proportion P, namely Var (P) = P(1-P)/n, the FN rate is expected to be estimated with a standard error of no more than 7.3%. This is considered to be a suitable level of precision. The width of the 90% CI for the FN rate is expected to be less than ± 12%.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
5/02/2018
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
30
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9508 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment postcode(s) [1] 18249 0
3168 - Clayton

Funding & Sponsors
Funding source category [1] 298154 0
Commercial sector/Industry
Name [1] 298154 0
TEVA pharmaceuticals
Country [1] 298154 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
Haematology research
McCulloch House, level 1
Monash medical centre
246 Clayton rd Clayton.
VIC 3168
Country
Australia
Secondary sponsor category [1] 297243 0
None
Name [1] 297243 0
Address [1] 297243 0
Country [1] 297243 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 299169 0
Monash
Ethics committee address [1] 299169 0
Research Support Services
Monash Health
Level 2, I Block
Monash Medical Centre
246 Clayton Road
Clayton Victoria 3168
Ethics committee country [1] 299169 0
Australia
Date submitted for ethics approval [1] 299169 0
02/11/2017
Approval date [1] 299169 0
Ethics approval number [1] 299169 0

Summary
Brief summary
The aim of this study is to evaluate the safety and efficacy of a new medication called lipegfilgrastim to reduce a frequent complication of chemoimmunotherapy used to treat Non Hodgkin Lymphoma (NHL).

Who is it for?
You may be eligible to join this study if you are aged 18 years or older, have a confirmed diagnosis of NHL requiring chemoimmunotherapy, and are at risk of febrile neutropenia.

Study details
All participants in this study will receive preventive treatment with a drug called lipegfilgrastim. Lipegfilgrastim is a growth factor that stimulates the bone marrow to produce neutrophils, white cells that help fight infection. Lipegfilgrastim is administered via an injection under the skin 24-72 hours after each dose of chemotherapy. Nursing staff will administer the growth factor. In conjuction with your treating haematologist, you will be monitored until approximately 14-21 days you complete your last cycle of chemotherapy. There will also be a follow up phone call 3 months after completing the study. During the study, you will undergo medical consultation, physical examination and regular blood tests (all but one are additional to 'standard of care' for your condition)

This trial will produce safety and efficacy data for this preventive treatment and may reduce a complication of NHL chemoimmunotherapy.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 79526 0
Dr Maciej Tatarczuch
Address 79526 0
Haematology research
McCulloch House, level 1
Monash medical centre
246 Clayton rd Clayton.
3168 VIC
Country 79526 0
Australia
Phone 79526 0
+61 03 9594 4044
Fax 79526 0
Email 79526 0
[email protected]
Contact person for public queries
Name 79527 0
Micheleine Uhe
Address 79527 0
Haematology research
McCulloch House, level 1
Monash medical centre
246 Clayton rd Clayton.
3168 VIC
Country 79527 0
Australia
Phone 79527 0
+61 03 9594 4044
Fax 79527 0
Email 79527 0
[email protected]
Contact person for scientific queries
Name 79528 0
Maciej Tatarczuch
Address 79528 0
Haematology research
McCulloch House, level 1
Monash medical centre
246 Clayton rd Clayton.
3168 VIC
Country 79528 0
Australia
Phone 79528 0
+61 03 9594 4044
Fax 79528 0
Email 79528 0
[email protected]

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No Supporting Document Provided



Results publications and other study-related documents

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