Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12612001045808
Ethics application status
Approved
Date submitted
14/09/2012
Date registered
2/10/2012
Date last updated
27/08/2021
Date data sharing statement initially provided
17/05/2019
Date results provided
17/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
A Phase 3 open-label randomized study to
compare the efficacy and safety of rituximab
plus lenalidomide versus rituximab plus
chemotherapy followed by rituximab in subjects
with previously untreated follicular lymphoma (ALLG NHL27)
Scientific title
A Phase 3 open-label randomized study to
compare the efficacy and safety of rituximab
plus lenalidomide versus rituximab plus
chemotherapy followed by rituximab in subjects
with previously untreated follicular lymphoma
Secondary ID [1] 281062 0
ALLG NHL27
Secondary ID [2] 281236 0
www.clinical trials. gov NCT01476787
Secondary ID [3] 281328 0
www.clinical trials. gov NCT01650701
Universal Trial Number (UTN)
Trial acronym
RELEVANCE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
follicular lymphoma 287423 0
Condition category
Condition code
Cancer 287757 287757 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
6 cycles of rituximab 375mg/m^2 on days 1,8,15,22 of cycle 1, day 1 of cycles 2-6 in conjunction with 20 mg daily oral lenalidomide on days 2-22 every 28 days.
Responding patients will continue to receive 375mg/m^2 rituximab intravenously (iv) every 8 weeks for 12 cycles together with a response adjusted dose of lenalidomide (patients exhibiting complete remission (CR) receive 12 cycles of 10mg daily on days 2-22 of 28 day cycles; patients exhibiting partial response (PR) receive an additional 3 or 6 cycles of 20 mg daily oral lenalidomide on days 2-22 every 28 days) until they achieve a CR, at which time they will continue to receive 10mg oral lenalidomide on days 2-22 of 28 day cycles for either 9 or 6 cycles. Patients who remain in PR will receive 10mg oral lenalidomide days 2-22 of 28 day cycles for the remaining 6 cycles.)
All responding patients will receive a total of 18 cycles of lenalidomide. Patients who do not respond will be withdrawn from treatment.
Intervention code [1] 285517 0
Treatment: Drugs
Comparator / control treatment
rituximab chemotherapy consisiting of a physician's choice of chemotherapy between
(i) 6 x 21 day cycles of rituximab (375mg/m^2 i.v on day 1 of each cycle), cyclophosphamide (750mg/m^2 i.v on day 1 of each cycle), doxorubicin (50mg/m^2 i.v on day 1 of each cycle), vincristine, (1.4mg/m^2 i.v on day 1 of each cycle) prednisolone (40mg/m^2 per oral on days 1-5 of each cycle)(R-CHOP) followed by 2x21 day cycles of 375mg/m^2 iv rituximab and 7 weeks later responding patients continue with 375mg/m^2 iv rituximab every 8 weeks for 12 cycles
or
(ii) 8x 21 day cycles of rituximab (375mg/m^2 i.v on day 1 of each cycle), cyclophosphamide rituximab (750mg/m^2 i.v on day 1 of each cycle), vincristine (1.4mg/m^2 i.v on day 1 of each cycle), prednisolone (rituximab (40mg/m^2 i.v on days 1-5 of each cycle) (CVP) followed by 7 weeks later responding patients continue with 375mg/m^2 iv rituximab ever 8 weeks for 12 cycles
Control group
Active

Outcomes
Primary outcome [1] 287780 0
The primary objective of the study is to compare the efficacy of rituximab plus lenalidomide to rituximab plus chemotherapy followed by rituximab in patients with previously untreated follicular lymphoma. Efficacy determination will be based upon the co-primary endpoints of complete response (CR/CRu) rate at 120 weeks and progression free survival (PFS) assessed by the international review committee (IRC) using the independent working group (IWG) (Cheson, 1999) criteria.
Timepoint [1] 287780 0
120 weeks for CR; for PFS from randomization into the study to the first observation of documented disease
progression or death due to any cause, or censored at the last patient visit
Secondary outcome [1] 298817 0
Time to Treatment Failure (TTF)
Timepoint [1] 298817 0
TTF will be measured from the date of randomization to the date of first documented treatment
discontinuation for any reason, including disease progression, treatment toxicity, and deaths.
Secondary outcome [2] 298818 0
Event Free Survival (EFS)
Timepoint [2] 298818 0
EFS will be measured from the date of randomization to the date of first documented progression, relapse, and initiation of a new anti-lymphoma treatment or death by any cause. Responding patients and patients who are lost to follow up will be censored at their last tumor assessment date.
Secondary outcome [3] 298819 0
Time to Next Anti-Lymphoma Treatment (TTNLT)
Timepoint [3] 298819 0
TTNLT will be measured from the date of randomization to the date of first documented administration of any new anti-lymphoma treatment (chemotherapy, radiotherapy, radioimmunotherapy, immunotherapy) or censored at the last patient visit
Secondary outcome [4] 298821 0
Overall Survival (OS)
Timepoint [4] 298821 0
End of trial; approximately when the first accrued patient has received 10 years follow up.

Eligibility
Key inclusion criteria
1. Histologically confirmed CD20+ follicular lymphoma grade 1, 2 or 3a as assessed by the investigators:
2. Have no prior systemic treatment for lymphoma.
3. Must be in need of treatment as evidenced by at least one of the following criteria:
Bulky disease defined as:
-a nodal or extranodal (except spleen) mass > 7cm in its
greater diameter or,
-involvement of at least 3 nodal or extranodal sites (each
with a diameter greater than >3 cm)
Presence of at least one of the following B symptoms:
-fever (>38 degrees Celcius) of unclear etiology
-night sweats
-weight loss greater than 10% within the prior 6 months
Symptomatic splenomegaly
Compression syndrome (ureteral, orbital, gastrointestinal)
Any one of the following cytopenias due to lymphoma:
-hemoglobin < 10g/dL (6.25 mmol/L)
-platelets <100 x 10^9/L , or
-absolute neutrophil count (ANC) < 1.5 x 10^9/L
Pleural or peritoneal serous effusion (irrespective of cell
content)
LDH> upper limit of normal (ULN) or beta 2 microglobulin > ULN
4. Bi-dimensionally measurable disease with at least one mass lesion > 2cm that was not previously irradiated.
5. Stage II, III or IV disease.
6. Must be > or = to 18 years and sign an informed consent.
7. Performance status less than or equal to 2 on the ECOG scale.
8. Adequate hematological function (unless abnormalities are related to lymphoma infiltration of the bone marrow) within 28 days prior to signing informed consent, including:
-Absolute neutrophil count (ANC) greater than or equal to 1.5 x 10^9/L
-Platelet count greater than or equal to 75 x 10^9/L
-Hemoglobin greater than or equal to 8.0 g/dl (5 mmol/L)
9. Must be able to adhere to the study visit schedule and other protocol requirements.
10. Females of childbearing potential (FCBP) receiving lenalidomide must:
-Have two negative pregnancy tests as verified by the study
doctor prior to starting study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the subject practices complete abstinence from heterosexual contact.
-Either commit to complete abstinence from heterosexual
contact(which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy.
11. Male patients receiving lenalidomide must:
Must practice complete abstinence or agree to use a condom
during sexual contact with a pregnant female or a female of
childbearing potential while participating in the study, during
dose interruptions and for at least 28 days following study
drug discontinuation, even if he has undergone a successful
vasectomy.
Agree to not donate semen during study drug therapy and for 28 days after discontinuation of study drug therapy.
12. All patients receiving lenalidomide must:
Have an understanding that the study drug could have a potential teratogenic risk.
Agree to abstain from donating blood while taking study drug therapy and for 28 days after discontinuation of study drug therapy.
Agree not to share study medication with another person.
Agree to be counseled about pregnancy precautions and risk of fetal exposure
Females must agree to abstain from breastfeeding during study participation and for at least 28 days after study drug
discontinuation.
13. For all patients receiving Rituximab:
Women must not breast feed and must use effective
contraception must not be pregnant and agree not to become pregnant during participation in the trial and during the 6 months thereafter. Men must agree not to father a child during participation in the trial and during the 6 months thereafter.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Clinical evidence of transformed lymphoma by investigator assessment.
2. Grade 3b follicular lymphoma.
3. Patients taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 10 mg/day prednisolone (over these 4 weeks).
4. Major surgery (excluding lymph node biopsy) within 28 days prior to signing informed consent.
5. Seropositive for or active viral infection with hepatitis B virus (HBV):
-HBsAg positive
-HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral DNA
Note:
-Patients who are HBsAg negative, anti-HBs positive and/or anti HBc positive but viral DNA negative are eligible
-Patients who are seropositive due to a history of hepatitis B vaccine are eligible.
6. Known seropositive for, or active infection hepatitis C virus (HCV).
7. Known seropositive for, or active viral infection with human immunodeficiency virus (HIV).
8. Life expectancy < 6 months.
9. Known sensitivity or allergy to murine products.
10. Prior history of malignancies, other than follicular lymphoma, unless the subject has been free of the disease for greater than or equal to 10 years. Exceptions include a history of previously treated:
a. Localized non-melanoma skin cancer
b. Carcinoma in situ of the cervix
11. Prior use of lenalidomide.
12. Neuropathy > Grade 1.
13. Presence or history of CNS involvement by lymphoma.
14. Patients who are at a high risk for a thromboembolic event and are not willing to take venous thromboembolic (VTE) prophylaxis.
15. Any of the following laboratory abnormalities:
-serum aspartate transaminase (AST/SGOT) or alanine
transaminase (ALT/SGPT) > 3x upper limit of normal (ULN),
except in patients with documented liver or pancreatic
involvement by lymphoma
-total bilirubin > 2.0 mg/dl (34 µmol/L) except in cases of Gilberts Syndrome and documented liver involvement by lymphoma
-creatinine clearance of < 30 mL/min
16. Uncontrolled intercurrent illness.
17. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form.
18. Pregnant or lactating females.
19. Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study, or which confounds the ability to interpret data from the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients will be enrolled centrally and allocated to a treatment arm centrally.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Random number generation using a computer programme
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
15/01/2013
Actual
3/09/2014
Date of last participant enrolment
Anticipated
Actual
13/10/2014
Date of last data collection
Anticipated
31/05/2027
Actual
Sample size
Target
1000
Accrual to date
Final
775
Recruitment in Australia
Recruitment state(s)
NSW,VIC,ACT,QLD,SA,WA,TAS
Recruitment outside Australia
Country [1] 4491 0
France
State/province [1] 4491 0
Country [2] 4492 0
Belgium
State/province [2] 4492 0
Country [3] 4493 0
United States of America
State/province [3] 4493 0
Country [4] 4494 0
Spain
State/province [4] 4494 0

Funding & Sponsors
Funding source category [1] 285844 0
Other Collaborative groups
Name [1] 285844 0
Australasian Leukaemia and Lymphoma Group
Country [1] 285844 0
Australia
Primary sponsor type
Other Collaborative groups
Name
The Lymphoma academic research organisation
Address
Centre Hospitalier Lyon Sud - Secteur Sainte Eugenie – Batiment 6D - 69495 Pierre Benite
Cedex
Country
France
Secondary sponsor category [1] 284665 0
Other Collaborative groups
Name [1] 284665 0
Australasian Leukaemia and Lymphoma Group
Address [1] 284665 0
Ground Floor, 35, Elizabeth Street
Richmond
VIC 3121
Country [1] 284665 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 287864 0
Sydney Local Health District (SLHD)
Ethics committee address [1] 287864 0
Ethics committee country [1] 287864 0
Australia
Date submitted for ethics approval [1] 287864 0
01/12/2012
Approval date [1] 287864 0
29/01/2014
Ethics approval number [1] 287864 0
HREC/14/CRGH/19

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

Contacts
Principal investigator
Name 34595 0
Dr Pauline Warburton
Address 34595 0
Director of Haematology Haematology Department Wollongong Hospital Private Mail Bag 8808 South Coast Mail Centre Wollongong, NSW, 2521
Country 34595 0
Australia
Phone 34595 0
+61 2 4253 4009
Fax 34595 0
Email 34595 0
[email protected]
Contact person for public queries
Name 17842 0
Delaine Smith
Address 17842 0
Ground Floor, 35, Elizabeth Street
Richmond
VIC 3121
Country 17842 0
Australia
Phone 17842 0
+61 3 8373 9701
Fax 17842 0
Email 17842 0
[email protected]
Contact person for scientific queries
Name 8770 0
Pauline Warburton
Address 8770 0
Director of Haematology
Haematology Department
Wollongong Hospital
Private Mail Bag 8808
South Coast Mail Centre
Wollongong, NSW, 2521
Country 8770 0
Australia
Phone 8770 0
+61 2 4253 4009
Fax 8770 0
Email 8770 0
[email protected]

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 Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.