Early Stage Follicular Lymphoma WHO Grade 1/2 or 3aPhase 3FORTplusNCT05045664
Early Stage Follicular LymphOma and RadioTherapy PLUS Anti-CD20 Antibody
A Phase 3 study testing Standard and Experimental in people with Early Stage Follicular Lymphoma WHO Grade 1/2 or 3a, run by Heidelberg University at 12 sites in Germany.
Trial summary
The MIR study proved the effect of Rituximab in combination with a localized irradiation given in a standard dose. Together with the TROG 99.03 trial, this led to the recommendation of using this combined approach in early stage nodal follicular lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Early Stage Follicular Lymphoma WHO Grade 1/2 or 3a
- What is being tested?
- Standard and Experimental
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 12 sitesGermany
- Study dates
- 6 Jul 2022to 30 Jun 2030
- Phase
- Phase 3
- 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
- • Centrally reviewed CD20-positive follicular lymphoma grade 1/2 or 3a based on WHO classification (2008)
- Untreated (radiation-, chemo- or immunotherapy) nodal follicular lymphoma (including involvement of Waldeyer´s ring)
- Age: ≥18 years
- ECOG: 0-2
- Stage: clinical stage I or II (Ann Arbor classification) based on FDG-PET Staging
- Risk profile: Largest diameter of the lymphoma ≤ 7 cm (sectional images)
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- Written informed consent and willingness to cooperate during the course of the trial
- Adequate bone marrow capacity: ANC ≥ 1.5 x 103/ml, thrombocytes ≥ 100000 x 10 3/ml, hemoglobin ≥ 10 g/dL
- Capability to understand the intention and the consequences of the clinical trial
- Adequate contraception for men and women of child-bearing age during therapy and 18 months thereafter
Who cannot join
- Extra nodal manifestation of follicular lymphoma
- Secondary cancer in the patient's medical history (exclusion: basalioma, spinalioma, melanoma in situ, bladder cancer T1a, non-metastasized solid tumor in constant remission, which was diagnosed >3 years ago)
- Serious disease interfering with a regular therapy according to the study protocol, e.g: congenital or acquired immune-deficiency syndromes, active infections including viral hepatitis, uncontrolled concomitant diseases including significant cardiovascular or pulmonary disease
- Severe psychiatric disease
- Pregnancy / lactation
- Known hypersensitivity against Obinutuzumab or Rituximab drugs with similar chemical structure or any other additive of the pharmaceutical formula of the study drug
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- Active hepatitis B infection (inactive hepatitis B infections require additional prophylactic anti-viral medication for 1 year (e.g. Lamivudin, Entecavir, Tenofovir)
- Participation in another interventional trial or follow-up period of a competing trial which can influence the results of this current trial
- Creatinine > 1.5 times the upper limit of normal (ULN) (unless creatinine clearance normal), or calculated creatinine clearance < 40 mL/min
- AST or ALT > 2.5 × ULN
- Total bilirubin ≥ 1.5 × ULN
- INR > 1.5 × ULN
- PTT or aPTT > 1.5 × the ULN
Trial locations and contacts
12 sites in 1 country. Contact the study team or a site near you to ask about taking part.
12 sites in 1 country
Germany12 sites, 12 recruiting
- Recruiting
Vivantes Klinikum Berlin
Berlin, 10967
Christian Scholz, MD, christianw.scholz@vivantes.de
- Recruiting
University of Essen
Essen, 45147
- Recruiting
University of Göttingen
Göttingen, 37075
Stefan Rieken, MD, stefan.rieken@med.uni-goettingen.de
- Recruiting
University Hospital Heidelberg
Heidelberg, 69120
Klaus Herfarth, MD, +496221568202, klaus.herfarth@med.uni-heidelberg.de
Julia Meissner, MD
- Recruiting
Strahlentherapie KH Maria Hilf
Mönchengladbach, 41063
Ursula Nestle, MD, +49-2161-8921801, Ursula.nestle@mariahilf.de
- Recruiting
LMU München
Munich, 81377
Martin Dreyling, MD, Martin.dreyling@med.uni-muenchen.de
- Recruiting
Technische Universität München
Munich, 81675
Simon Heidegger, MD, Simon.heidegger@tum.de
- Recruiting
Krankenhaus Barmherzige Brüder
Regensburg, 93049
Bernhard Heilmeier, MD, Bernhard.Heilmeier@barmherzige-regensburg.de
- Recruiting
University of Rostock
Rostock, 18057
Guido Hildebrandt, MD, guido.hildebrandt@med.uni-rostock.de
- Recruiting
Katharinen Hospital Stuttgart
Stuttgart
- Recruiting
University of Tübingen
Tübingen, 72076
Stefan Wirths, MD, Stefan.Wirths@med.uni-tuebingen.de
- Recruiting
University of Ulm
Ulm, 89081
Christian Buske, MD, Christian.buske@uni-ulm.de
About this study
The MIR study proved the effect of Rituximab in combination with a localized irradiation given in a standard dose. Together with the TROG 99.03 trial, this led to the recommendation of using this combined approach in early stage nodal follicular lymphoma. The GAZAI study is currently looking for the effect of a low dose radiotherapy of 2x2 Gy in combination with Obinutuzumab. The combination seems to show a high CR rate based on the 50% of the patients. This is in contrast to the FORT trial, which showed an inferiority of the 4 Gy dose compared to the standard dose (24 Gy) in terms of response and progression free survival.
The goal of the FORTplus trial is to prove (1) the non-inferiority of LDRT (4Gy) in a combined approach with an anti-CD20-antibody. In case of non-inferiority, a possible (2) superiority of the Obinutuzumab + LDRT should be tested against Rituximab + standard dose using the same test set.
The radiation dose can significantly be reduced to 16% of the standard dose if (1) is confirmed. Knowing the data of the FORT trial, this would have a significant influence on the treatment of the disease worldwide even if the difference in the CR rate at week 18 is not as high as currently in the historical comparison expected.
- Being tested
- Standard, Experimental
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
StandardRadiation
12 x 2 Gy involved site radiotherapy plus Rituximab
ExperimentalRadiation
2 x2 Gy involved site radiotherapy plus Obinutuzumab
StandardDrug
Also called Rituximab
Rituximab with 12 x 2 Gy involved site radiotherapy
ExperimentalDrug
Also called Obinutuzumab
Obinutuzumab with 2 x2 Gy involved site radiotherapy
| Study group | Role | What they receive |
|---|---|---|
| Standard | Active comparator | Standard dose (24 Gy) involved site radiotherapy plus Rituximab Receives: Radiation: Standard; Drug: Standard |
| Experimental | Experimental | ow-dose (4 Gy) involved site radiotherapy in combination with Obinutuzumab Receives: Radiation: Experimental; Drug: Experimental |
What is being measured
The primary outcome is the main question the study is designed to answer.
Morphologic complete response
Rate of morphologic complete response based on CT scan in patients with initially remaining lymphoma
Measured: Week 18
Secondary outcomes (5)
Metabolic complete response
Rate of metabolic complete response based on FDG PET in patients with initially remaining lymphoma
Measured: week 18
Morphologic response
Morphologic CR in patients with initially remaining lymphoma
Measured: Month 6
PFS
Progression-free survival (PFS) of each treatment arm
Measured: 2 years
Frequency and extent of Toxicity
Toxicity (NCI-CTC criteria, version 5) of all patients
Measured: until month 30
Overall survival
Overall survival (OS) of each treatment arm
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2021
- Study start6 Jul 2022
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Jun 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Early Stage Follicular Lymphoma WHO Grade 1/2 or 3aStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Controlled, open, randomised, 2 parallel groups, multi-centre, national, treatment phase III trial
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Klaus Herfarth, MD, Heidelberg University
- Investigators
- Klaus Herfarth, MD, Principal investigator, Heidelberg University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05045664
- Sponsor's protocol ID
- 2021-000362-15
- Acronym
- FORTplus
- Status last verified
- Apr 2026
- First submitted
- 25 Aug 2021
- Last updated
- 28 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Konig L, Dreyling M, Durig J, Engelhard M, Hohloch K, Viardot A, Witzens-Harig M, Kieser M, Klapper W, Pott C, Herfarth K. Therapy of nodal Follicular Lymphoma (WHO grade 1/2) in clinical stage I/II using response adapted Involved Site Radiotherapy in combination with Obinutuzumab (Gazyvaro) - GAZAI Trial (GAZyvaro and response adapted Involved-site Radiotherapy): a study protocol for a single-arm, non-randomized, open, national, multi-center phase II trial. Trials. 2019 Aug 30;20(1):544. doi: 10.1186/s13063-019-3614-y.
PubMed 31470902Hoskin PJ, Kirkwood AA, Popova B, Smith P, Robinson M, Gallop-Evans E, Coltart S, Illidge T, Madhavan K, Brammer C, Diez P, Jack A, Syndikus I. 4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT): a randomised phase 3 non-inferiority trial. Lancet Oncol. 2014 Apr;15(4):457-63. doi: 10.1016/S1470-2045(14)70036-1. Epub 2014 Feb 24.
PubMed 24572077Herfarth K, Borchmann P, Schnaidt S, Hohloch K, Budach V, Engelhard M, Viardot A, Engenhart-Cabillic R, Keller U, Reinartz G, Eich HT, Witzens-Harig M, Hess CF, Dorken B, Durig J, Wiegel T, Hiddemann W, Hoster E, Pott C, Dreyling M. Rituximab With Involved Field Irradiation for Early-stage Nodal Follicular Lymphoma: Results of the MIR Study. Hemasphere. 2018 Nov 30;2(6):e160. doi: 10.1097/HS9.0000000000000160. eCollection 2018 Dec.
PubMed 31723798Hoskin P, Popova B, Schofield O, Brammer C, Robinson M, Brunt AM, Madhavan K, Illidge T, Gallop-Evans E, Syndikus I, Clifton-Hadley L, Kirkwood AA. 4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2021 Mar;22(3):332-340. doi: 10.1016/S1470-2045(20)30686-0. Epub 2021 Feb 1.
PubMed 33539729
Study at a glance
From the registry record, last updated by the sponsor on 28 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early Stage Follicular LymphOma and RadioTherapy PLUS Anti-CD20 Antibody
- ClinicalTrials.gov ID
- NCT05045664
- Acronym / sponsor ID
- FORTplus / 2021-000362-15
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Heidelberg UniversityUniversity, hospital or other
- Study start
- 6 Jul 2022 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Jun 2030 (estimated)
- First posted
- 16 Sep 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The MIR study proved the effect of Rituximab in combination with a localized irradiation given in a standard dose. Together with the TROG 99.03 trial, this led to the recommendation of using this combined approach in early stage nodal follicular lymphoma. The GAZAI study is currently looking for the effect of a low dose radiotherapy of 2x2 Gy in combination with Obinutuzumab. The combination seems to show a high CR rate based on the 50% of the patients. This is in contrast to the FORT trial, which showed an inferiority of the 4 Gy dose compared to the standard dose (24 Gy) in terms of response and progression free survival.
The goal of the FORTplus trial is to prove (1) the non-inferiority of LDRT (4Gy) in a combined approach with an anti-CD20-antibody. In case of non-inferiority, a possible (2) superiority of the Obinutuzumab + LDRT should be tested against Rituximab + standard dose using the same test set.
The radiation dose can significantly be reduced to 16% of the standard dose if (1) is confirmed. Knowing the data of the FORT trial, this would have a significant influence on the treatment of the disease worldwide even if the difference in the CR rate at week 18 is not as high as currently in the historical comparison expected.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Controlled, open, randomised, 2 parallel groups, multi-centre, national, treatment phase III trial
| Arm | Type | Receives |
|---|---|---|
| Standard | Active comparator | Radiation: Standard, Drug: StandardStandard dose (24 Gy) involved site radiotherapy plus Rituximab |
| Experimental | Experimental | Radiation: Experimental, Drug: Experimentalow-dose (4 Gy) involved site radiotherapy in combination with Obinutuzumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- • Centrally reviewed CD20-positive follicular lymphoma grade 1/2 or 3a based on WHO classification (2008)
Key exclusion criteria (13 listed)
- Extra nodal manifestation of follicular lymphoma
- Secondary cancer in the patient's medical history (exclusion: basalioma, spinalioma, melanoma in situ, bladder cancer T1a, non-metastasized solid tumor in constant remission, which was diagnosed >3 years ago)
- Serious disease interfering with a regular therapy according to the study protocol, e.g: congenital or acquired immune-deficiency syndromes, active infections including viral hepatitis, uncontrolled concomitant diseases including significant cardiovascular or pulmonary disease
- Severe psychiatric disease
- Pregnancy / lactation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Standard12 x 2 Gy involved site radiotherapy plus Rituximab | Radiation | Standard |
| Experimental2 x2 Gy involved site radiotherapy plus Obinutuzumab | Radiation | Experimental |
| StandardAlso: RituximabRituximab with 12 x 2 Gy involved site radiotherapy | Drug | Standard |
| ExperimentalAlso: ObinutuzumabObinutuzumab with 2 x2 Gy involved site radiotherapy | Drug | Experimental |
Primary outcome
Morphologic complete response
Time frame: Week 18
Rate of morphologic complete response based on CT scan in patients with initially remaining lymphoma
5 secondary outcomes
Metabolic complete response
Time frame: week 18
Morphologic response
Time frame: Month 6
PFS
Time frame: 2 years
Frequency and extent of Toxicity
Time frame: until month 30
Overall survival
Time frame: 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Apr 2026.
- Background: PubMed 31470902Konig L, Dreyling M, Durig J, Engelhard M, Hohloch K, Viardot A, Witzens-Harig M, Kieser M, Klapper W, Pott C, Herfarth K. Therapy of nodal Follicular Lymphoma (WHO grade 1/2) in clinical stage I/II using response adapted Involved Site Radiotherapy in combination with Obinutuzumab (Gazyvaro) - GAZAI Trial (GAZyvaro and response adapted Involved-site Radiotherapy): a study protocol for a single-arm, non-randomized, open, national, multi-center phase II trial. Trials. 2019 Aug 30;20(1):544. doi: 10.1186/s13063-019-3614-y.
- Background: PubMed 24572077Hoskin PJ, Kirkwood AA, Popova B, Smith P, Robinson M, Gallop-Evans E, Coltart S, Illidge T, Madhavan K, Brammer C, Diez P, Jack A, Syndikus I. 4 Gy versus 24 Gy radiotherapy for patients with indolent lymphoma (FORT): a randomised phase 3 non-inferiority trial. Lancet Oncol. 2014 Apr;15(4):457-63. doi: 10.1016/S1470-2045(14)70036-1. Epub 2014 Feb 24.
- Results publication: PubMed 31723798Herfarth K, Borchmann P, Schnaidt S, Hohloch K, Budach V, Engelhard M, Viardot A, Engenhart-Cabillic R, Keller U, Reinartz G, Eich HT, Witzens-Harig M, Hess CF, Dorken B, Durig J, Wiegel T, Hiddemann W, Hoster E, Pott C, Dreyling M. Rituximab With Involved Field Irradiation for Early-stage Nodal Follicular Lymphoma: Results of the MIR Study. Hemasphere. 2018 Nov 30;2(6):e160. doi: 10.1097/HS9.0000000000000160. eCollection 2018 Dec.
- Results publication: PubMed 33539729Hoskin P, Popova B, Schofield O, Brammer C, Robinson M, Brunt AM, Madhavan K, Illidge T, Gallop-Evans E, Syndikus I, Clifton-Hadley L, Kirkwood AA. 4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2021 Mar;22(3):332-340. doi: 10.1016/S1470-2045(20)30686-0. Epub 2021 Feb 1.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Klaus Herfarth, MD principal investigator
Heidelberg University
12 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Standard and Experimental in people with Early Stage Follicular Lymphoma WHO Grade 1/2 or 3a, run by Heidelberg University at 12 sites in Germany.
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 10 inclusion and 13 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: looking for participants now, as of the sponsor's last update on 28 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 12 sites in Germany. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Contact Klaus Herfarth, MD (+496221568202, klaus.herfarth@med.uni-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Morphologic complete response (time frame: Week 18). 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 NCT05045664, which also lists 4 linked publications.
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 28 Apr 2026.