Early Stage Follicular LymphOma and RadioTherapy PLUS Anti-CD20 Antibody

NCT05045664 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 2021-000362-15
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 12

Brief 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. 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.

Conditions

Early Stage Follicular Lymphoma WHO Grade 1/2 or 3a

Outcome Measures

Primary Outcomes (1)

• Morphologic complete response

  Rate of morphologic complete response based on CT scan in patients with initially remaining lymphoma

  Week 18

Secondary Outcomes (5)

• Metabolic complete response

  week 18

• Morphologic response

  Month 6

• PFS

  2 years

• Frequency and extent of Toxicity

  until month 30

• Overall survival

  2 years

Study Arms (2)

Standard

ACTIVE COMPARATOR

Standard dose (24 Gy) involved site radiotherapy plus Rituximab

Radiation: Standard; Drug: Standard

Experimental

EXPERIMENTAL

ow-dose (4 Gy) involved site radiotherapy in combination with Obinutuzumab

Radiation: Experimental; Drug: Experimental

Interventions

Standard RADIATION

12 x 2 Gy involved site radiotherapy plus Rituximab

Standard

Experimental RADIATION

2 x2 Gy involved site radiotherapy plus Obinutuzumab

Experimental

Eligibility Criteria

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

You may qualify if:

• 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)
• 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

You may not qualify if:

• Extra nodal manifestation of follicular lymphoma
• 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
• 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

Sponsors & Collaborators

• Heidelberg University: lead

Study Sites (12)

Vivantes Klinikum Berlin

Berlin, 10967, Germany

RECRUITING

University of Essen

Essen, 45147, Germany

RECRUITING

University of Göttingen

Göttingen, 37075, Germany

RECRUITING

University Hospital Heidelberg

Heidelberg, 69120, Germany

RECRUITING

Strahlentherapie KH Maria Hilf

Mönchengladbach, 41063, Germany

RECRUITING

LMU München

Munich, 81377, Germany

RECRUITING

Technische Universität München

Munich, 81675, Germany

RECRUITING

Krankenhaus Barmherzige Brüder

Regensburg, 93049, Germany

RECRUITING

University of Rostock

Rostock, 18057, Germany

RECRUITING

Katharinen Hospital Stuttgart

Stuttgart, Germany

RECRUITING

University of Tübingen

Tübingen, 72076, Germany

RECRUITING

University of Ulm

Ulm, 89081, Germany

RECRUITING

Related Publications (4)

• 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.

  PMID: 31470902 BACKGROUND

• Hoskin 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.

  PMID: 24572077 BACKGROUND

• Herfarth 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.

  PMID: 31723798 RESULT

• Hoskin 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.

  PMID: 33539729 RESULT

MeSH Terms

Interventions

Rituximab; obinutuzumab

Intervention Hierarchy (Ancestors)

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

Study Officials

• Klaus Herfarth, MD

  Heidelberg University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Klaus Herfarth, MD

CONTACT

+496221568202; klaus.herfarth@med.uni-heidelberg.de

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Chair, Department of Radiation Oncology

Model Details: Controlled, open, randomised, 2 parallel groups, multi-centre, national, treatment phase III trial

Study Record Dates

• First Submitted: August 25, 2021
• First Posted: September 16, 2021
• Study Start: July 6, 2022
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): June 30, 2030
• Last Updated: April 28, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

DE (12)