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

NCT03245021 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: CA209-676
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 5

Brief Summary

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

Conditions

Follicular Lymphoma

Outcome Measures

Primary Outcomes (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

  1st 16 weeks of therapy

Secondary Outcomes (6)

• Overall toxicity

  5 years

• Response rate

  1st 16 weeks of therapy

• Complete response rate

  6 months post completion of induction treatment

• Time to treatment failure

  5 years

• Progression free survival

  5 years

Study Arms (1)

Open-Label

OTHER

Opdivo - Single-arm open label study

Drug: Opdivo

Interventions

Opdivo DRUG

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

Also known as: Rituximab

Open-Label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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:
• 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.
• 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
• 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

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Dr. Eliza Hawkes: lead
• Bristol-Myers Squibb: collaborator

Study Sites (5)

Ballarat Health

Ballarat, Victoria, Australia

Location

Eastern Health

Box Hill, Victoria, 3128, Australia

Location

Monash Health

Clayton, Victoria, Australia

Location

Austin Health

Heidelberg, Victoria, 3084, Australia

Location

St Vincent's Hospital

Melbourne, Victoria, Australia

Location

Related Publications (1)

• 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.

  PMID: 39853272 DERIVED

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

Nivolumab; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Antibodies, Monoclonal, Murine-Derived

Study Officials

• Eliza Hawkes, MD

  Austin Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Chief Principal Investigator

Model Details: Single Group Assignment

Study Record Dates

• First Submitted: August 7, 2017
• First Posted: August 10, 2017
• Study Start: September 7, 2017
• Primary Completion: May 11, 2022
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 30, 2024

Record last verified: 2024-07

Locations

AU (5)