Early Stage Follicular LymphOma and RadioTherapy PLUS Anti-CD20 Antibody

Phase 3

Recruiting

• Conditions: Early Stage Follicular Lymphoma WHO Grade 1/2 or 3a
• Interventions: Drug: Standard; Drug: Experimental

• Registration Number: NCT05045664
• Lead Sponsor: Heidelberg University

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-08-25
• Study First Submitted QC: 2021-09-12
• Study First Posted: 2021-09-16
• Study Start: 2022-07-06
• Status Verified: 2024-12
• Last Update Submitted: 2024-12-03
• Last Update Posted: 2024-12-06
• Primary Completion: 2026-12-31
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

• • 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

Exclusion Criteria

• 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
• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard	Standard	Standard dose (24 Gy) involved site radiotherapy plus Rituximab
Experimental	Experimental	ow-dose (4 Gy) involved site radiotherapy in combination with Obinutuzumab

Primary Outcome Measures

Name	Time	Method
Morphologic complete response	Week 18	Rate of morphologic complete response based on CT scan in patients with initially remaining lymphoma

Secondary Outcome Measures

Name	Time	Method
Metabolic complete response	week 18	Rate of metabolic complete response based on FDG PET in patients with initially remaining lymphoma
Morphologic response	Month 6	Morphologic CR in patients with initially remaining lymphoma
PFS	2 years	Progression-free survival (PFS) of each treatment arm
Frequency and extent of Toxicity	until month 30	Toxicity (NCI-CTC criteria, version 5) of all patients
Overall survival	2 years	Overall survival (OS) of each treatment arm

Trial Locations

Locations (12)

Vivantes Klinikum Berlin; 🇩🇪 Berlin, Germany

University of Essen; 🇩🇪 Essen, Germany

University of Göttingen; 🇩🇪 Göttingen, Germany

University Hospital Heidelberg; 🇩🇪 Heidelberg, Germany

LMU München; 🇩🇪 Munich, Germany

Technische Universität München; 🇩🇪 Munich, Germany

Strahlentherapie KH Maria Hilf; 🇩🇪 Mönchengladbach, Germany

Krankenhaus Barmherzige Brüder; 🇩🇪 Regensburg, Germany

University of Rostock; 🇩🇪 Rostock, Germany

Katharinen Hospital Stuttgart; 🇩🇪 Stuttgart, Germany

University of Tübingen; 🇩🇪 Tübingen, Germany

University of Ulm; 🇩🇪 Ulm, Germany