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Follicular LymphomaPhase 11stFLORNCT03245021

Nivolumab Plus Rituximab in First-line Follicular Lymphoma gr 1-3A

A Phase 1 study testing Opdivo in people with Follicular Lymphoma, run by Dr. Eliza Hawkes at 5 sites in Australia.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial summary

Firstline treatment for grade 13a Follicular Lymphoma using Opdivo (nivolumab) plus Rituximab: The 1st FLOR trial Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Follicular Lymphoma
What is being tested?
Opdivo
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
39 participants
Where
5 sitesAustralia
Study dates
7 Sep 2017to Jun 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age ≥ 18 years.
  • 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.
  • No previous chemotherapy, or other investigational drug for this indication apart from focal radiotherapy.
  • 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.
  • 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.
  • Deemed to need treatment by treating investigator. Reasons for treatment can include, but are not limited to:
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  • 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).
  • Adequate bone marrow function including:
  • Haemoglobin >9.0 g/dL
  • White blood cells (WBC) ≥2000/μL
  • Neutrophils >1.5 x 109/L
  • Platelets >100 x 109/L at the time of study entry, unless attributed to bone marrow infiltration by lymphoma.
  • 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
  • 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
  • Women must not be breastfeeding
  • 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
  • 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.
  • 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.
  • Written, informed consent.

Who cannot join

  • Grade 3B follicular lymphoma, transformed follicular lymphoma, other indolent lymphomas.
  • 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.
  • Central nervous system, meningeal involvement or cord compression by lymphoma.
  • 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.
  • 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.
  • Past history of interstitial lung disease.
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  • 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.
  • Any other serious active disease.
  • Any positive test result for hepatitis B or hepatitis C virus during screening indicating acute or chronic infection.
  • Any positive test for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
  • 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
  • Medical or psychiatric conditions that compromise the patient's ability to give informed consent.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Australia5 sites

  • Ballarat Health

    Ballarat, Victoria

  • Eastern Health

    Box Hill, Victoria, 3128

  • Monash Health

    Clayton, Victoria

  • Austin Health

    Heidelberg, Victoria, 3084

  • St Vincent's Hospital

    Melbourne, Victoria

Other trials in Australia

About this study

Official title: First-line Treatment for Grade 1-3A Follicular Lymphoma Using Opdivo (Nivolumab) Plus Rituximab: The 1st FLOR Study

Firstline treatment for grade 13a Follicular Lymphoma using Opdivo (nivolumab) plus Rituximab: The 1st FLOR trial

Read the detailed description

This study will involve participants with a condition called Follicular NonHodgkin Lymphoma (Follicular Lymphoma).

The main purpose of this study is to see if it is safe to give drug Nivolumab before and in combination with drug Rituximab and to see how effective Nivolumab is in patients who have had no previous drug treatment for their lymphoma. In particular, we will be monitoring for any specific side effects which may be increased by adding Nivolumab to Rituximab treatment, including monitoring of the immune system.

Participants will be reviewed at baseline and prior to each cycle of treatment for toxicity, scans will be performed at baseline, after 4 cycles of nivolumab, after 8 cycles of nivolumab +/rituximab and at 6 months post induction treatment phase and following completion of treatment, participants will be followed up for a total of 5 years (every 3 months for 2 years, every 6 months for 3 years). In participants with relapsed disease, these will be followed for survival every 3 months.

Being tested
Opdivo
Medical subject headings
Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • OpdivoDrug

    Also called Rituximab

    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

Study groups in NCT03245021
Study groupRoleWhat they receive
Open-LabelOtherOpdivo - Single-arm open label study
Receives: Drug: Opdivo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: 1st 16 weeks of therapy

Secondary outcomes (6)

  1. Overall toxicity

    As determined by rate of toxicity grade 3 or higher per CTCAE v4.0

    Measured: 5 years

  2. Response rate

    Response Rate to Nivolumab + Rituximab according to the Lugano classification for Response Criteria for Non-Hodgkin Lymphoma

    Measured: 1st 16 weeks of therapy

  3. Complete response rate

    Response Rate to Nivolumab + Rituximab according to the Lugano classification for Response Criteria for Non-Hodgkin Lymphoma

    Measured: 6 months post completion of induction treatment

  4. Time to treatment failure

    Time to progression

    Measured: 5 years

  5. Progression free survival

    Duration of survival without relapse or non-relapse mortality

    Measured: 5 years

  6. Overall survival

    Overall toxicity as assessed by CTCAE v4.0

    Measured: 5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2017
  2. Study start7 Sep 2017
  3. Primary completion11 May 2022
  4. Study completionJun 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Single Group Assignment
Masking
None (open label)
Enrolment
39 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03245021
Sponsor's protocol ID
CA209-676
Acronym
1stFLOR
Status last verified
Oct 2026
First submitted
7 Aug 2017
Last updated
29 Oct 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided: IPD is the property of the Sponsor (Austin Health). Results from the research intends to be published/presented in relevant publications/conferences for colleague review

Publications

  • Barraclough A, Lee ST, Burgess M, Churilov L, Chong G, Lee D, Gilbertson M, Fancourt T, Manos K, Ritchie DS, Koldej RM, Scott AM, Keane C, Hawkes EA. Nivolumab and rituximab in treatment-naive follicular lymphoma: the phase 2 1st FLOR study. Blood Adv. 2025 Mar 25;9(6):1432-1441. doi: 10.1182/bloodadvances.2024015487.

    PubMed 39853272

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Opdivo in people with Follicular Lymphoma, run by Dr. Eliza Hawkes at 5 sites in Australia.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: 1st 16 weeks of therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03245021, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.

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