Early Stage Follicular LymphOma and RadioTherapy PLUS Anti-CD20 Antibody (FORTplus)

Heidelberg University

Status and phase: Enrolling; Phase 3

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

Treatments: Drug: Experimental; Drug: Standard

Study type: Interventional

Funder types: Other

Identifiers

NCT05045664

2021-000362-15

Details and patient eligibility

About

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.

Enrollment: 100 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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100 participants in 2 patient groups

Standard

Active Comparator group

Description:

Standard dose (24 Gy) involved site radiotherapy plus Rituximab

Treatment:

Drug: Standard

Drug: Standard

Experimental

Experimental group

Description:

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

Treatment:

Drug: Experimental

Drug: Experimental