nodal follicular lymphoma grade 1 or grade 2 in the clinical stage I or II (Ann Arbor classification) MedDRA version: 23.0 Level: PT Classification code 10029602 Term: Non-Hodgkin's lymphoma stage I System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 23.0 Level: PT Classification code 10029603 Term: Non-Hodgkin's lymphoma stage II System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: GAZYVARO®
Product Name: GAZYVARO
Product Code: RO5072759
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Obinutuzumab
CAS Number: 949142-50-1
Current Sponso
Sponsors
Ruprecht-Karls-University Heidelberg, Medical Faculty represented by University Hospital Heidelberg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Centrally reviewed CD20-positive follicular lymphoma grade 1/2 based on WHO classification (2008) • Untreated (radiation-, chemo- or immunotherapy) nodal lymphoma (including involvement of Waldeyer´s ring) • Age: =18 years • ECOG: 0-2 • Stage: clinical stage I or II (Ann Arbor classification) • 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 hematologic function (unless abnormalities are related to NHL), defined as follows: Hemoglobin = 9.0 g/dL; absolute neutrophil count = 1.5 × 109/L, Platelet count = 75 × 109/L • 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 • Patients with non-active hepatitis B infection (HBsAg neg/HBcAB pos/HBV DNA neg) under 1-year prophylactic anti-viral therapy (e.g. Entecavir® or Tenofovir®) possible (see also 5.6. Prior and Concomitant Disease) Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 19 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 74
Exclusion criteria
Exclusion criteria: • Extra nodal manifestation • Secondary cancer in the patients medical history (exclusion: basalioma, spinalioma, melanoma in situ, bladder cancer T1a, non-metastasized solid tumor in constant remission, which was diagnosed >3 years ago • Concomitant diseases: congenital or acquired immune-deficiency syndromes, active infections including viral hepatitis (serology positive for HBsAg or HBcAb in combination positive HBV DNA), uncontrolled concomitant diseases including significant cardiovascular or pulmonary disease (see also 5.6. Prior and Concomitant Disease) • Severe psychiatric disease • Pregnancy / lactation • Known hypersensitivity against Gazyvaro (Obinutuzumab) or drugs with similar chemical structure or any other additive of the pharmaceutical formula of the study drug • 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 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 |
|---|---|
| Main Objective: The rate of metabolic CR after low-dose radiotherapy in combination with Gazyvaro (Obinutuzumab) for early stage nodal follicular lymphoma will be assessed. In addition, the feasibility of a response adapted approach using FDG-PET/CT regarding success (PFS, rates of remission, analysis of recurrences) and safety in combination with Gazyvaro will be assessed. The results will be historically compared to the results of the MIR trial regarding morphologic response in week 7 and the quality of life (secondary endpoints). Additional secondary endpoints are PFS, the site of recurrences in the three subgroups (1. PET negative after initial staging; 2. PET negative in week 18; 3. PET positive in week 18). Primary Evaluation of the rate of metabolic CR after low-dose involved site radiotherapy in combination with Gazyvaro (Obinutuzumab) in early stage nodal follicular lymphoma in order to avoid conventional full dose IF radiotherapy. ;Secondary Objective: Secondary Efficacy and safety of a response adapted radiation dose treatment schedule. ;Primary end point(s): Metabolic complete response (CR) in patients with initially remaining lymphoma judged by FDG-PET/CT;Timepoint(s) of evaluation of this end point: in week 18 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Morphologic CR, PR, SD, PD in week 7, week 18 and month 6 in patients with initially remaining lymphoma judged by CT/MRI • Historical comparison of the morphologic response with MIR data (using MabThera); The comparison of the CR rate in week 7 will allow for a comparison of the two different CD20 antibodies. Due to the restricted patient numbers no matched pair analysis will be possible • Progression free survival (PFS) of all treated patients (2 years after individual treatment start) • Toxicity (NCI-CTC criteria, version 4.03) of all patients • Relapse rate and pattern of recurrence of all treated patients at all follow-up visits. • Overall survival (OS) of all treated patients (2 years) • Quality of life according EORTC QLQ C30 and FACT-Lym questionnaires at inclusion and in week 18, month 12, and 24 (all treated patients) • MRD response in peripheral blood: initially, week 18, months 6, 12, 18 and 24 (all treated patients). MRD is evaluated by the laboratory of C. Pott (Kiel) using at least the markers: t(14:18) PCR for MBR, 3’mbr, 5’mcr and MCR; clonal IGH rearrangements (FR1-3); clonal IGL rearrangements (IGK and Kappa-KDE);Timepoint(s) of evaluation of this end point: • Morphologic CR, PR, SD, PD in week 7, week 18 and month 6 • Historical comparison of the morphologic response with MIR data in week 7 • Progression free survival 2 years after individual treatment start • Relapse rate and pattern of recurrence at all follow-up visits • Overall survival (OS) (2 years) | — |
Countries
Germany
Contacts
Public ContactProf. Dr. med. Klaus Herfarth
Abteilung Radioonkologie & Strahlentherapie, Universitätsklinikum Heidelberg
Outcome results
None listed