Frontline Treatment of Follicular Lymphoma With AtezolizUmab and Obinutuzumab With and Without RadiOtherapy

NCT04962126 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: FLUORO
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 3

Brief Summary

This single-arm phase II interventional study aims to assess disease response to, and toxicity of, a combination of obinutuzumab and atezolizumab, with or without radiotherapy, in treatment naive Follicular Lymphoma. The study will involve an induction phase and a maintenance phase for responding participants, for up to 24 months. Response to treatment will be monitored using medical imaging and clinical assessment.

Conditions

Follicular Lymphoma

Keywords

Treatment naive advanced disease; anti PD-L1 antibody; anti-CD20 antibody

Outcome Measures

Primary Outcomes (1)

• Complete metabolic response rate according to Lugano response criteria

  Complete metabolic response (according to the Lugano response criteria) rate at end of induction (i.e. 6 cycles of obinutuzumab and atezolizumab with or without RT).

  At the end of cycle 6 (each cycle in the induction phase is 21 days)

Secondary Outcomes (4)

• Metabolic response rates according to Lugano and RECIL response criteria

  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).

• Progression free survival of treated participants

  0-42 months

• Overall survival of treated participants

  0-42 months

• Quantification of adverse events (according to CTCAEv5.0), including immune-related AEs (irAEs) in treated participants.

  0-27 months

Study Arms (1)

Treatment naive advanced follicular lymphoma

EXPERIMENTAL

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.

Drug: Obinutuzumab 25 MG/1 ML Intravenous Solution; Drug: Atezolizumab 1200 MG/40mL Intravenous Solution; Radiation: 4 Gy in 2 fractions

Interventions

Obinutuzumab 25 MG/1 ML Intravenous Solution DRUG

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.

Also known as: Gazyva

Treatment naive advanced follicular lymphoma

Atezolizumab 1200 MG/40mL Intravenous Solution DRUG

For intravenous infusion during induction phase only day 1 of each cycle q3/52 for up to 6 cycles.

Also known as: Tecentriq

Treatment naive advanced follicular lymphoma

4 Gy in 2 fractions RADIATION

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.

Treatment naive advanced follicular lymphoma

Eligibility Criteria

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

You may qualify if:

• Patient has provided written informed consent
• Male or female aged ≥ 18 years or older at written informed consent
• 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
• No previous chemotherapy, or other investigational drug for this indication apart from focal RT
• 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
• 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)
• 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

You may not qualify if:

• Patient has grade 3B FL, transformed FL or other indolent lymphoma
• 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
• Central nervous system, meningeal involvement, cord compression from lymphoma
• 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
• Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF- α 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
• 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
• 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)
• 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

Sponsors & Collaborators

• Olivia Newton-John Cancer Research Institute: lead
• Roche Products Pty Limited: collaborator
• Austin Health: collaborator
• Ballarat Health Services: collaborator

Study Sites (3)

Ballarat Health Service

Ballarat, Victoria, Australia

Location

Eastern Health

Box Hill, Victoria, 3128, Australia

Location

Austin Health

Heidelberg, Victoria, 3078, Australia

Location

MeSH Terms

Conditions

Lymphoma, Follicular

Interventions

obinutuzumab; atezolizumab

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

Study Officials

• Eliza Hawkes, MBBS

  Austin Health

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single arm phase II study with addition of involved site radiotherapy treatment in participants who achieve only PR/SD at first response assessment

Study Record Dates

• First Submitted: June 29, 2021
• First Posted: July 14, 2021
• Study Start: August 17, 2021
• Primary Completion: April 30, 2023
• Study Completion: July 1, 2025
• Last Updated: March 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

AU (3)