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Trial registered on ANZCTR


Registration number
ACTRN12613000106730
Ethics application status
Approved
Date submitted
21/01/2013
Date registered
29/01/2013
Date last updated
2/05/2019
Date data sharing statement initially provided
2/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 2 Study of patients treated for relapsed Follicular Lymphoma: with Revlimid (Registered Trademark) consolidation added to Rituximab maintenance therapy in those remaining Positron Emission Tomography (PET) positive (ALLG NHL26)
Scientific title
A Phase 2 Study of patients treated for relapsed Follicular Lymphoma: with Revlimid (Registered Trademark) consolidation added to Rituximab maintenance therapy in those remaining Positron Emission Tomography (PET) positive
Secondary ID [1] 281814 0
ALLG NHL26
Universal Trial Number (UTN)
Trial acronym
RePLY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsed Follicular Lymphoma 288163 0
Condition category
Condition code
Cancer 288527 288527 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients will undergo a Positron Emission Tomography (PET) scan and then be assigned to the PET+ or PET- arm of the study.

PET scan preparation and procedure will take approximately 2 hours. Patients will also be required to fast for four hours prior to the scan. Diabetic patients should discuss fasting requirements with their doctor. Plain, unflavoured water may be consumed while fasting.

Postinducton PET- patients:
Rituximab 375mg/m2 by i.v or 1400mg s.c every 3 months for 2 years.

Postinducton PET+ patients:
Rituximab 375mg/m2 by i.v or 1400mg s.c every 3 months for 2 years, plus Lenalidomide consolidation therapy.
Lenalidomide capsules will be administered at a starting dose of 10mg orally per day for 21 days of a 28 day cycle, for 6 months.
After this patients will be reassessed via PET scan and treatment will be adapted based on these results:
Patients remaining PET+ will continue Lenalidomide at a dose of 15mg/day for a maximum total of 2 years Lenalidomide therapy.
Patients becoming PET- will continue Lenalidomide at a dose of 10mg/day for a maximum total of 2 years Lenalidomide therapy.
If there is PET determined progression patients will discontinue Lenalidomide but continue to be followed.
Intervention code [1] 286364 0
Treatment: Drugs
Intervention code [2] 286365 0
Treatment: Other
Comparator / control treatment
Postinducton PET- patients:
Rituximab 375mg/m2 by i.v or 1400mg s.c every 3 months for 2 years
Control group
Active

Outcomes
Primary outcome [1] 288684 0
To determine the percentage of patients converting from PET+ after reinduction immunochemotherapy to PET- after 6 months of commencing Lenalidomide consolidation.

PET+ will be defined as cut-off =3 using 5 point scale (5PS), and determined by a consensus response interpretation by local and central PET physician.
Timepoint [1] 288684 0
After 6 months of Lenalidomide treatment
Secondary outcome [1] 300757 0
To describe the toxicity and tolerability of consolidation and subsequent maintenance of Lenalidomide-Rituximab.

Toxicity and tolerability will be measured as:
Worst grade of adverse events.
Incidence of serious adverse events
Treatment breaks due to toxicity
Dose reductions due to toxicity
Frequency of and reasons for patient withdrawal
Timepoint [1] 300757 0
From registration to the end of follow-up (18 months)
Secondary outcome [2] 300758 0
To describe the PET conversion rates in PET+ patient subgroups with score of either 3, 4 or 5 on the 5PS
Timepoint [2] 300758 0
From registration to the end of follow-up (18 months)
Secondary outcome [3] 300759 0
To describe the PET conversion rate after 12 months of Lenalidomide therapy for patients remaining PET+ at the 6 month assessment.

PET+ will be defined as cut-off =3 using 5 point scale (5PS), and determined by a consensus response interpretation by local and central PET physician.
Timepoint [3] 300759 0
12 months
Secondary outcome [4] 300760 0
To determine the clinical efficacy of Lenalidomide –Rituximab consolidation and maintenance: Progression free survival (PFS), Overall survival (OS).

Progression free survival (PFS): PFS is based on conventional Computed Tomography (CT) criteria and defined as the time from the post-induction CT scan done in conjunction with PET scan to the first observation of disease progression or death from any cause.

Overall survival (OS): OS is defined as time from the post-induction CT scan done in conjunction with PET scan to death from any cause.
Timepoint [4] 300760 0
From registration to the end of follow-up (18 months)
Secondary outcome [5] 300761 0
To describe Health-Related Quality of Life (HRQOL) separately for postinduction PET- and PET+ patients.
Timepoint [5] 300761 0
From registration to the end of follow-up (18 months)
Secondary outcome [6] 300762 0
To describe the PFS and OS in postinduction PET- patients receiving Rituximab maintenance.

Progression free survival (PFS): PFS is based on conventional Computed Tomography (CT) criteria and defined as the time from the post-induction CT scan done in conjunction with PET scan to the first observation of disease progression or death from any cause.

Overall survival (OS): OS is defined as time from the post-induction CT scan done in conjunction with PET scan to death from any cause.
Timepoint [6] 300762 0
From registration to the end of follow-up (18 months)

Eligibility
Key inclusion criteria
Relapsed follicular lymphoma having obtained conventional Stable disease (SD), Partial Response (PR), Complete remission unconfirmed (CRu) or Complete Remission (CR) after most recent reinduction therapy. Response assessment within 4-6 weeks of day 1 of last chemotherapy cycle.

Relapsed disease must be either Stage III or IV, or Stage II bulky disease defined as a tumor diameter of greater than or equal to 7 cm.

Symptomatic disease in need of systemic immunochemotherapy treatment as defined by the investigator.

Patient has provided written informed consent

Life expectancy at least 6 months

An Eastern Co-operative Oncology Group (ECOG) performance status score of less than or equal to 2 at Screening
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Patients with demonstrated histological transformation

Patients who have:
>6 prior cycles of Fludarabine
Allogeneic transplant
Prior exposure to Lenalidomide

Patients who have had a negative PET scan during re-induction therapy

Patients with poor haemopoeitic recovery 4-8 weeks post chemotherapy

Patients with inadequate liver function

Patients with severe renal impairment

Medial contraindication to rituximab

CNS involvement with lymphoma

Any uncontrolled inter-current illness

HIV, Hepatitis B or Hepatitis C infection

Pregnant or breastfeeding women

Prior malignancy, other than FL, unless free from disease / treatment for greater than or equal to 5 years. Exceptions include localised non-melanoma skin cancer and carcinoma in situ., and prostate cancer TNM Stage T1a or T1b

Patients at high risk of venous thromboembolism who are not willing to take prophylaxis

Patients with any psychiatric , social or geographic circumstance that would preclude protocol compliance

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Once registered patients will undergo protocol PET scan and then be assigned by the central PET physician to the PET+ or PET- arm of the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
n/a
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Patients will be registered in the study until 16 post-induction PET+ evaluable patients have been included. 16 patients provides 80% power with type I error of 5% for a one sided exact test for proportion assuming a conversion rate of at least 50% as worthy of further evaluation and a conversion rate of 20% or lower as unacceptable. Assuming conservatively that 25% of the patients will be PET+ after re-induction and 20% of PET+ patients will not be considered evaluable, 80 patients are expected to be registered on study.

Recruitment
Recruitment status
Recruiting
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)
ACT,NSW,NT,QLD,TAS,VIC
Recruitment hospital [1] 8164 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 8165 0
Prince of Wales Hospital - Randwick
Recruitment hospital [3] 8166 0
St George Hospital - Kogarah
Recruitment hospital [4] 8167 0
Wollongong Hospital - Wollongong
Recruitment hospital [5] 8169 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [6] 8170 0
Gold Coast University Hospital - Southport
Recruitment hospital [7] 8171 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [8] 8172 0
Western Hospital - Footscray - Footscray
Recruitment hospital [9] 8173 0
Royal Darwin Hospital - Tiwi
Recruitment hospital [10] 8174 0
Royal Hobart Hospital - Hobart
Recruitment hospital [11] 8175 0
Orange Health Service - Orange
Recruitment postcode(s) [1] 16234 0
0810 - Tiwi
Recruitment postcode(s) [2] 16226 0
2031 - Randwick
Recruitment postcode(s) [3] 16230 0
2050 - Camperdown
Recruitment postcode(s) [4] 16225 0
2139 - Concord
Recruitment postcode(s) [5] 16227 0
2217 - Kogarah
Recruitment postcode(s) [6] 16228 0
2500 - Wollongong
Recruitment postcode(s) [7] 16236 0
2800 - Orange
Recruitment postcode(s) [8] 16233 0
3011 - Footscray
Recruitment postcode(s) [9] 16232 0
4102 - Woolloongabba
Recruitment postcode(s) [10] 16231 0
4215 - Southport
Recruitment postcode(s) [11] 16235 0
7000 - Hobart

Funding & Sponsors
Funding source category [1] 286601 0
Other Collaborative groups
Name [1] 286601 0
Australasian Leukaemia and Lymphoma Group
Address [1] 286601 0
35 Elizabeth St, Richmond, Vic, 3121.
Country [1] 286601 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Australasian Leukaemia and Lymphoma Group
Address
35 Elizabeth St, Richmond, Vic, 3121.
Country
Australia
Secondary sponsor category [1] 285388 0
None
Name [1] 285388 0
Address [1] 285388 0
Country [1] 285388 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 288675 0
Sydney Local Health District HREC CRGH
Ethics committee address [1] 288675 0
Concord Repatriation General Hospital
Concord, NSW 2139
Ethics committee country [1] 288675 0
Australia
Date submitted for ethics approval [1] 288675 0
01/04/2013
Approval date [1] 288675 0
17/06/2013
Ethics approval number [1] 288675 0
TBC
Ethics committee name [2] 297801 0
University of Tasmania
Ethics committee address [2] 297801 0
Office of Research Services
University of Tasmania
Private Bag 1
Hobart
Tasmania 7001
Ethics committee country [2] 297801 0
Australia
Date submitted for ethics approval [2] 297801 0
Approval date [2] 297801 0
13/12/2013
Ethics approval number [2] 297801 0
H0013606
Ethics committee name [3] 297802 0
Human Research Ethics Committee of the Northern Territory department of Health
Ethics committee address [3] 297802 0
John Mathews Building
Royal Darwin Hospital Campus
Rocklands Drive
Casuarina
NT 0810
Ethics committee country [3] 297802 0
Australia
Date submitted for ethics approval [3] 297802 0
Approval date [3] 297802 0
18/08/2014
Ethics approval number [3] 297802 0
2014-2205

Summary
Brief summary
The prognosis for patients with FL has significantly improved during the last decade with the incorporation of Rituximab into therapy. Rituximab maintenance has become a standard of care after initial rituximab-chemotherapy for remission induction.

Lenalidomide is an immune system modulating drug that has anti-lymphoma properties demonstrated in smaller studies of patients with relapsed/refractory Diffuse large B-cell lymphoma.

Lenalidomide consolidation added to Rituximab maintenance therapy may convert PET+ patients to PET-, without causing unmanageable side effects.

Positron emission tomography (PET) is a medical imaging tool that can detect cancer in its early stages, help to monitor cancer treatment and check if the cancer is coming back.

Lay Summary:
Follicular lymphoma is the most common type of slow growing non Hodgkin lymphoma. Treatments and outcomes have improved considerably in the last 10 years with the introduction of the drug, rituximab to standard chemotherapy treatments. However, the disease returns repeatedly in many patients. PET scanning is a type of test used by doctors to outline where the lymphoma is in the body. PET scans will ‘light up’ the areas of active follicular lymphoma. Such positive PET scans after the end of treatment indicate that it is likely the lymphoma will return soon.
This study is for patients with returned disease who have already received treatment again and so are at even
higher risk of disease returning yet again. Patients will receive rituximab and up to 24 months of another drug, lenalidomide, which is designed to help the body’s own immune system to keep the lymphoma away. The study will decide if the extra treatment with lenalidomide can change the scan result to negative and improve patient outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 37222 0
A/Prof Judith Trotman
Address 37222 0
Concord Repatriation General Hospital
Hospital Road
Concord, NSW, 2139
Country 37222 0
Australia
Phone 37222 0
+61 2 97677243
Fax 37222 0
Email 37222 0
Judith.Trotman@health.nsw.gov.au
Contact person for public queries
Name 37223 0
Ms Delaine Smith
Address 37223 0
ALLG,
35 Elizabeth St, Richmond, VIC, 3121.
Country 37223 0
Australia
Phone 37223 0
+61 3 96569010
Fax 37223 0
Email 37223 0
delaine.smith@allg.org.au
Contact person for scientific queries
Name 37224 0
A/Prof Judith Trotman
Address 37224 0
Concord Repatriation General Hospital
Hospital Road
Concord, NSW, 2139
Country 37224 0
Australia
Phone 37224 0
+61 2 97677243
Fax 37224 0
Email 37224 0
Judith.Trotman@health.nsw.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No individual participant data will be publicly available as it is the aggregate data that is under investigation.
What supporting documents are/will be available?
No other documents available
Summary results
No Results