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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03245021




Registration number
NCT03245021
Ethics application status
Date submitted
7/08/2017
Date registered
10/08/2017
Date last updated
15/01/2019

Titles & IDs
Public title
Nivolumab Plus Rituximab in First-line Follicular Lymphoma gr 1-3A
Scientific title
First-line Treatment for Grade 1-3A Follicular Lymphoma Using Opdivo (Nivolumab) Plus Rituximab: The 1st FLOR Study
Secondary ID [1] 0 0
CA209-676
Universal Trial Number (UTN)
Trial acronym
1stFLOR
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 - Opdivo

Other: Open-Label - Opdivo - Single-arm open label study


Treatment: Drugs: Opdivo
All patients will receive:
Nivolumab 240mg IV q2-weekly for four cycles
Patients in complete remission (CR):
Nivolumab 240mg IV q2-weekly for four further cycles (8 in total)
Patients with partial response (PR), stable disease (SD), asymptomatic or minor progressive disease (PD) post 4cycles receive:
Nivolumab 240mg IV plus rituximab 375mg/m2 IV q2-weekly for four cycles
Patients in CR:
Nivolumab 240mg IV q2-weekly for four further cycles (8 in total)
Patients with PR, SD, asymptomatic or minor PD post 4 cycles receive:
Nivolumab 240mg IV plus rituximab 375mg/m2 IV q2-weekly for four cycles

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
To evaluate the feasibility and safety of combination nivolumab and rituximab as determined by the proportion of toxicity grade 3 or higher per CTCAE v4.0 occurring on induction treatment (ie first 16 weeks of therapy) - As determined by rate of toxicity grade 3 or higher per CTCAE v4.0
Timepoint [1] 0 0
1st 16 weeks of therapy
Secondary outcome [1] 0 0
Overall toxicity - As determined by rate of toxicity grade 3 or higher per CTCAE v4.0
Timepoint [1] 0 0
5 years
Secondary outcome [2] 0 0
Response rate - Response Rate to Nivolumab + Rituximab according to the Lugano classification for Response Criteria for Non-Hodgkin Lymphoma
Timepoint [2] 0 0
1st 16 weeks of therapy
Secondary outcome [3] 0 0
Complete response rate - Response Rate to Nivolumab + Rituximab according to the Lugano classification for Response Criteria for Non-Hodgkin Lymphoma
Timepoint [3] 0 0
6 months post completion of induction treatment
Secondary outcome [4] 0 0
Time to treatment failure - Time to progression
Timepoint [4] 0 0
5 years
Secondary outcome [5] 0 0
Progression free survival - Duration of survival without relapse or non-relapse mortality
Timepoint [5] 0 0
5 years
Secondary outcome [6] 0 0
Overall survival - Overall toxicity as assessed by CTCAE v4.0
Timepoint [6] 0 0
5 years

Eligibility
Key inclusion criteria
1. Age = 18 years.

2. Histologically proven Follicular non Hodgkin lymphoma (FL) grades 1-3A according to
the current World Health Organization classification.29 The B cell nature of the
proliferation must be verified by the positivity with an anti-CD20 antibody.

3. No previous chemotherapy, or other investigational drug for this indication apart from
focal radiotherapy.

4. Stage II-IV disease (Ann Arbor criteria). Stage II disease must not be encompassable
in a single radiotherapy field and being considered for definitive radiotherapy.

5. Eastern Collaborative Oncology Group (ECOG) performance status 0 to 1 unless
attributable to lymphoma, in which case patients of performance status 2 are also
eligible.

6. Deemed to need treatment by treating investigator. Reasons for treatment can include,
but are not limited to:

a. Any nodal or extranodal tumour mass >7cm AND/OR multiple extranodal disease sites b.
Involvement of at least 3 sites each with diameter >3cm c. Symptomatic splenic enlargement
d. Organ involvement/compression e. Ascites or pleural effusion f. Lactate Dehydrogenase
(LDH) elevated g. Presence of systemic symptoms h. Disease progression in preceding 3
months i. Evidence of marrow infiltration with marrow compromise. (eg Hb, WBC or plt count
below lower limit of institutional normal range).

g) Adequate bone marrow function including:

1. Haemoglobin >9.0 g/dL

2. White blood cells (WBC) =2000/µL

3. Neutrophils >1.5 x 109/L

4. Platelets >100 x 109/L at the time of study entry, unless attributed to bone marrow
infiltration by lymphoma.

h) Adequate renal function with serum creatinine =1.5 x ULN or creatinine clearance (CrCl)
= 40mL/min (using Cockroft-Gault formula) Female CrCl = (140 - age in years) x weight (kg)
x 0.85 72 x serum creatinine (mg/dL) Male CrCl = (140 - age in years) x weight (kg) x 1.00
72 x serum creatinine (mg/dL) i) Adequate hepatic function with AST/ALT =3x ULN and total
bilirubin =1.5 x ULN (except subjects with Gilbert syndrome, who can have a total bilirubin
=3 mg/dL or =51.3 µmol/L) j) Life expectancy > 3 months. k) Patients of childbearing
potential willing to adhere to contraceptive precautions

1. Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy
test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 24 hours prior to
the start of study treatment

2. Women must not be breastfeeding

3. WOCBP must use appropriate method(s) of contraception to avoid pregnancy for 23 weeks
(30 days plus five half-lives of nivolumab) post-treatment completion

4. Men who are sexually active with WOCBP must use any contraceptive method with a
failure rate of less than 1% per year. They must agree to adhere to contraception for
a period of 31 weeks after the last day of nivolumab.

5. Azoospermic males and WOCBP who are continuously not heterosexually active are exempt
from contraceptive requirements. However, they must still undergo pregnancy testing as
described in this section.

l) Written, informed consent.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Grade 3B follicular lymphoma, transformed follicular lymphoma, other indolent
lymphomas.

2. 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.

3. Central nervous system, meningeal involvement or cord compression by lymphoma.

4. Patients with active, known or suspected autoimmune disease. Patients with well
controlled type I diabetes mellitus, coeliac disease, residual hypothyroidism due to
autoimmune condition only requiring hormone replacement, vitiligo or psoriasis not
requiring systemic treatment, or other conditions not expected to recur in the absence
of an external trigger are permitted to enrol.

5. Subjects with a condition requiring systemic treatment with either corticosteroids (>
10mg daily prednisone equivalents) or other immunosuppressive medications within 14
days of study drug administration. Inhaled or topical steroids, and adrenal
replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of
active autoimmune disease.

6. Past history of interstitial lung disease.

7. Prior malignancy active within the previous 3 years except for locally curable cancers
that have been apparently cured, such as basal or squamous cell skin cancer,
superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast.

8. Any other serious active disease.

9. Any positive test result for hepatitis B or hepatitis C virus during screening
indicating acute or chronic infection.

10. Any positive test for human immunodeficiency virus (HIV) or known acquired
immunodeficiency syndrome (AIDS)

11. Any history of severe hypersensitivity reactions to other monoclonal antibodies. A
history of allergy or intolerance (unacceptable AEs) to study drug components or
Polysorbate-80-containing infusions

12. Medical or psychiatric conditions that compromise the patient's ability to give
informed consent.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
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 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
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)
VIC
Recruitment hospital [1] 0 0
Ballarat Health - Ballarat
Recruitment hospital [2] 0 0
Eastern Health - Box Hill
Recruitment hospital [3] 0 0
Monash Health - Clayton
Recruitment hospital [4] 0 0
Austin Health - Heidelberg
Recruitment hospital [5] 0 0
St Vincent's Hospital - Melbourne
Recruitment postcode(s) [1] 0 0
- Ballarat
Recruitment postcode(s) [2] 0 0
3128 - Box Hill
Recruitment postcode(s) [3] 0 0
- Clayton
Recruitment postcode(s) [4] 0 0
3084 - Heidelberg
Recruitment postcode(s) [5] 0 0
- Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
Dr. Eliza Hawkes
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Bristol-Myers Squibb
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Firstline treatment for grade 13a Follicular Lymphoma using Opdivo (nivolumab) plus
Rituximab: The 1st FLOR trial
Trial website
https://clinicaltrials.gov/show/NCT03245021
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Eliza Hawkes, MD
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
Eliza Hawkes, MD
Address 0 0
Country 0 0
Phone 0 0
+61 3 9496 5763
Fax 0 0
Email 0 0
eliza.hawkes@onjcri.org.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03245021