Early Stage Follicular Lymphoma WHO Grade 1/2 or 3a
Conditions
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.
Interventions
RADIATIONStandard
12 x 2 Gy involved site radiotherapy plus Rituximab
RADIATIONExperimental
2 x2 Gy involved site radiotherapy plus Obinutuzumab
Sponsors
Heidelberg University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Controlled, open, randomised, 2 parallel groups, multi-centre, national, treatment phase III trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Morphologic complete response | Week 18 | Rate of morphologic complete response based on CT scan in patients with initially remaining lymphoma |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Germany
Contacts
CONTACTKlaus Herfarth, MD
PRINCIPAL_INVESTIGATORKlaus Herfarth, MD
Heidelberg University
Outcome results
None listed