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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04962126


Additional trial details provided through ANZCTR are available at the end of this record.


Registration number
NCT04962126
Ethics application status
Date submitted
29/06/2021
Date registered
14/07/2021

Titles & IDs
Public title
Frontline Treatment of Follicular Lymphoma With AtezolizUmab and Obinutuzumab With and Without RadiOtherapy
Scientific title
Frontline Treatment of Follicular Lymphoma With AtezolizUmab and Obinutuzumab With and Without RadiOtherapy
Secondary ID [1] 0 0
FLUORO
Universal Trial Number (UTN)
Trial acronym
FLUORO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Follicular 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 - Obinutuzumab 25 MG/1 ML Intravenous Solution
Treatment: Drugs - Atezolizumab 1200 MG/40mL Intravenous Solution
Treatment: Other - 4 Gy in 2 fractions

Experimental: Treatment naive advanced follicular lymphoma - All consenting participants will be receive an intravenous infusion of Obinutuzumab (1000mg) + Atezolizumab (1200mg) q3/52 x 6 cycles (plus 1000mg Obinutuzumab on day 8 and 15 of cycle 1). Responding participants (PR or SD) who do not achieve a CR at the end of cycle 2 will receive involved site radiotherapy (4Gy, 2 fractions) between cycle 3 and 4. At the end of cycle 6 and completion of the induction phase, responding participants (CR/PR/SD) will receive maintenance phase Obinutuzumab (1000mg IV) q8/52 for up to 12 cycles.


Treatment: Drugs: Obinutuzumab 25 MG/1 ML Intravenous Solution
For intravenous infusion during:

Induction phase: Day 1, 8 and 15 of cycle 1 \& Day 1 of cycle 2-6 (q3/52); Maintenance phase: Day 1 of each cycle (q8/52) for up to 12 cycles.

Treatment: Drugs: Atezolizumab 1200 MG/40mL Intravenous Solution
For intravenous infusion during induction phase only day 1 of each cycle q3/52 for up to 6 cycles.

Treatment: Other: 4 Gy in 2 fractions
Involved site radiotherapy will only be administered to participants to achieve a PR/SD after at restaging after cycle 2, treatment will be between cycle 3 and 4 of induction treatment.
Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Complete metabolic response rate according to Lugano response criteria
Timepoint [1] 0 0
At the end of cycle 6 (each cycle in the induction phase is 21 days)
Secondary outcome [1] 0 0
Metabolic response rates according to Lugano and RECIL response criteria
Timepoint [1] 0 0
After 2 cycles (each cycle in the induction phase is 21 days), at the end of induction phase (6 cycles or 126 days) and at the end of maintenance phase (up to 2 years).
Secondary outcome [2] 0 0
Progression free survival of treated participants
Timepoint [2] 0 0
0-42 months
Secondary outcome [3] 0 0
Overall survival of treated participants
Timepoint [3] 0 0
0-42 months
Secondary outcome [4] 0 0
Quantification of adverse events (according to CTCAEv5.0), including immune-related AEs (irAEs) in treated participants.
Timepoint [4] 0 0
0-27 months

Eligibility
Key inclusion criteria
1. Patient has provided written informed consent
2. Male or female aged = 18 years or older at written informed consent
3. Histologically proven FL grade 1-3A according to the current World Health Organisation classification (2016) including all morphological variants. The B-cell nature of the proliferation must be verified by the positivity with an anti-CD20 antibody
4. No previous chemotherapy, or other investigational drug for this indication apart from focal RT
5. Stage I disease not amenable to single-agent definitive-dose RT, stage II, III or IV (as per Ann Arbor criteria - see appendix 1), suitable for treatment with non-curative intent
6. At least one site of radiographically measurable disease not previously irradiated (at least one bi-dimensionally measurable site of disease: nodal disease >1.5 cm or an extranodal lesion > 1.0 cm in longest perpendicular diameter)
7. Deemed to need treatment by treating Investigator. Reasons for treatment can include, but are not limited to:

* Any nodal or extranodal tumour mass >7cm AND/OR multiple extranodal disease sites
* Involvement of at least 3 sites each with diameter >3cm
* Symptomatic splenic enlargement
* Organ involvement/compression
* Ascites or pleural effusion
* (LDH) elevated
* Presence of systemic symptoms
* Disease progression in preceding 3 months
* Evidence of marrow infiltration with marrow compromise. (e.g. haemoglobin, WBC or platelet count below lower limit of institutional normal range)
8. Adequate bone marrow function within 7 days prior to registration defined as:

* ANC =1.0x109/L
* WBC =2.0x109/L
* Platelets =100x109/L (with no platelet transfusion in the preceding 14 days)
* Haemoglobin =90 g/L (with no red blood cell transfusion in the preceding 14 days) Unless these are attributed to bone marrow infiltration by lymphoma. In cases were one or more results are lower than those specified above due to bone marrow infiltration by FL, patient may be eligible following consultation with the CPI.
9. Adequate organ function within 7 days prior to registration, defined as

* Total bilirubin =1.5 x upper ULN with the exception of patients with known Gilbert's syndrome may be included if their total bilirubin is =3.0 x ULN and direct bilirubin =1.5 x ULN)
* AST and(ALT) =3 x ULN
* Adequate renal function with serum creatinine =1.5 x ULN or CrCl = 40mL/min (using Cockroft-Gault formula, see Appendix 2)
* For patients not receiving therapeutic anticoagulation: INR and aPTT = 1.5 x ULN
* For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
10. ECOG performance status 0-2 (see Appendix 3)
11. Life expectancy greater than 6 months
12. Patients of childbearing potential must adhere to the following:

* Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration Note: A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (> 12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Müllerian agenesis). The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.
* Female patients of childbearing potential must be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the trial through to 18 months after the last dose of treatment. Women must refrain from donating eggs during this same period.

Note: The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception.
* Women must not be breastfeeding during study treatment and for 18 months after the last dose of obinutuzumab/study treatment.
* Male patients must agree to use an adequate method of contraception for the course of the trial through to 18 months after the last dose of treatment. Men must refrain from donating sperm during this same period.
13. Able to comply with the study protocol requirements and follow-up procedures.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patient has grade 3B FL, transformed FL or other indolent lymphoma
2. Requirement for urgent treatment due to life-threatening complications of the disease, for example: Compressive symptoms due to disease (which may or may not be bulky), such as superior vena caval obstruction; significant organ involvement causing compromise of organ function (including but not limited to liver/ renal obstruction, actual or impending spinal cord compression, uncontrolled pleural/pericardial effusions), malignant, symptomatic hypercalcaemia
3. Central nervous system, meningeal involvement, cord compression from lymphoma
4. Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
5. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF- a agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:

* Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study after Medical Monitor confirmation has been obtained
* Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids (= 10mg prednisolone for orthostatic hypotension or adrenal insufficiency are eligible for the study
6. Patients with active, known or suspected autoimmune disease, with the following exceptions:

* Well controlled type I diabetes mellitus
* Coeliac disease
* Residual hypothyroidism due to autoimmune condition only requiring hormone replacement
* Eczema or vitiligo or psoriasis not requiring systemic treatment and rash covering <10% of body surface area
* Other conditions not expected to recur in the absence of an external trigger
7. Past history of pneumonitis or lung disease including idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organising pneumonia (i.e., bronchiolitis obliterans, cryptogenic organising pneumonia)
8. Significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3 months prior to registration, unstable arrhythmia, or unstable angina
9. Prior organ transplantation or allogeneic bone marrow transplantation
10. Severe active infection with 4 weeks prior to registration , including, but not limited to, hospitalisation for complications of infection
11. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the patient's participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator
12. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
13. Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the screening visit through 18months after the last dose of trial treatment, for women and men respectively. Women of childbearing potential must have a negative serum pregnancy test result within 7 days prior to registration.
14. History of HIV (HIV 1/2 antibodies)
15. Active Hepatitis B (Patients with a negative hepatitis B surface antigen (HBsAg) test and a positive total hepatitis B core antibody test (HBcAg) at screening are eligible for the study provided that the screening hepatitis B virus (HBV) DNA test is negative or undetectable). Patients with known hepatitis B on current antiviral therapy are excluded
16. Active Hepatitis C (Patients are eligible with a negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test)
17. Administration of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment or anticipation that such a live attenuated vaccine will be required during the study. Influenza vaccination should be given during influenza season only (example: approximately March to October in the Southern Hemisphere). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior registration or at any time during the study treatment or within 5 months after the last dose of protocol treatment. B-cell recovery should be documented prior to administration of live vaccines.
18. Has a known history of active TB (Bacillus Tuberculosis)
19. History of severe allergic anaphylactic reactions to chimeric or humanised antibodies or fusion proteins
20. Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulations
21. Major surgical procedure, other than for diagnosis, within 4 weeks prior registration
22. History of malignancy within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year OS rate > 90%), such as adequately treated carcinoma in situ of the cervix, non melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or Stage I uterine cancer -

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 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
17/08/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/07/2025
Actual
Sample size
Target
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Ballarat Health Service - Ballarat
Recruitment hospital [2] 0 0
Eastern Health - Box Hill
Recruitment hospital [3] 0 0
Austin Health - Heidelberg
Recruitment postcode(s) [1] 0 0
- Ballarat
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
3078 - Heidelberg

Funding & Sponsors
Primary sponsor type
Other
Name
Olivia Newton-John Cancer Research Institute
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Roche Products Pty Limited
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
Austin Health
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Ballarat Health Services
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Eliza Hawkes, MBBS
Address 0 0
Austin Health
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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 not provided in https://clinicaltrials.gov/study/NCT04962126

Additional trial details provided through ANZCTR
Accrual to date
Recruiting in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 16
Ballarat Health Services (Base Hospital)
Recruitment hospital [2] 17
Austin Health - Austin Hospital
Recruitment hospital [3] 18
Sunshine Hospital
Recruitment hospital [4] 19
Box Hill Hospital
Recruitment postcode(s) [1] 21
3350
Recruitment postcode(s) [2] 22
3084
Recruitment postcode(s) [3] 23
3021
Recruitment postcode(s) [4] 24
3128
Funding & Sponsors
Funding source category [1] 48
Commercial sector/Industry
Name [1] 48
Roche Products Pty Ltd
Address [1] 48
Level 8, 30-34 Hickson Road Sydney NSW 2000
Country [1] 48
Australia
Primary sponsor
Charities/Societies/Foundations
Primary sponsor name
Olivia Newton-John Cancer Research Institute
Primary sponsor address
Level 5, Olivia Newton-John Cancer Research and Wellness Centre,
145 Studley Rd
Heidelberg, VIC 3084
Primary sponsor country
Australia
Ethics approval
Ethics application status
Approved
 
Public notes

Contacts
Principal investigator
Title 233 0
A/Prof
Name 233 0
Eliza Hawkes
Address 233 0
Austin Health, Medical Oncology L4, ONJ Building 145 Studley Rd Heidelberg
Country 233 0
Australia
Phone 233 0
+61394965000
Fax 233 0
Email 233 0
eliza.hawkes@austin.org.au
Contact person for public queries
Title 234 0
Dr
Name 234 0
Jodie Palmer
Address 234 0
Olivia Newton-John Cancer Research Institute L5, ONJ Building 145 Studley Rd Heidelberg, VIC 3084
Country 234 0
Australia
Phone 234 0
+61394963573
Fax 234 0
Email 234 0
trials@onjcri.org.au
Contact person for scientific queries
Title 235 0
Dr
Name 235 0
Jodie Palmer
Address 235 0
Olivia Newton-John Cancer Research Institute L5, ONJ Building 145 Studley Rd Heidelberg, VIC 3084
Country 235 0
Australia
Phone 235 0
+61394963573
Fax 235 0
Email 235 0
trials@onjcri.org.au