Stage I Follicular Lymphoma Grade 1 Clinical Trial
— GAZAIOfficial title:
Therapy of Nodal Follicular Lymphoma (WHO Grade 1/2) in Clinical Stage I/II Using Response Adapted Involved Site Radiotherapy in Combination With Gazyvaro
| Verified date | November 2023 |
| Source | Heidelberg University |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
Combined modality approach using Obitunuzumab and involved site low dose irradiation in early stage nodal follicular lymphoma. Radiation dose will be adapted for low-responders. Primary Objective: 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: Efficacy and safety of a response adapted radiation dose treatment schedule.
| Status | Active, not recruiting |
| Enrollment | 89 |
| Est. completion date | May 2024 |
| Est. primary completion date | November 11, 2021 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | Inclusion Criteria: - Centrally reviewed CD20-positive follicular lymphoma grade 1/2 based on WHO classification (2016) - 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 require prophylactic anti-viral therapy (e.g. Entecavir®) possible (see also 5.6. Prior and Concomitant Disease) Exclusion Criteria: - Extra nodal manifestation - 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 - 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 < 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 |
| Country | Name | City | State |
|---|---|---|---|
| Germany | Vivantes Klinikum | Berlin | |
| Germany | University of Cologne | Cologne | |
| Germany | University of Essen | Essen | |
| Germany | University of Frankfurt | Frankfurt | |
| Germany | University of Heidelberg | Heidelberg | |
| Germany | Klinikum Kempten | Kempten | |
| Germany | Site Marburg | Marburg | |
| Germany | LMU | Munich | |
| Germany | TU | Munich | |
| Germany | University of Muenster | Münster | |
| Germany | University of Tuebingen | Tuebingen | Baden-Wuerttemberg |
| Germany | University of Ulm | Ulm |
| Lead Sponsor | Collaborator |
|---|---|
| Heidelberg University | Roche Pharma AG |
Germany,
Haas RL, Poortmans P, de Jong D, Aleman BM, Dewit LG, Verheij M, Hart AA, van Oers MH, van der Hulst M, Baars JW, Bartelink H. High response rates and lasting remissions after low-dose involved field radiotherapy in indolent lymphomas. J Clin Oncol. 2003 Jul 1;21(13):2474-80. doi: 10.1200/JCO.2003.09.542. — View Citation
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. — View Citation
Mac Manus MP, Hoppe RT. Is radiotherapy curative for stage I and II low-grade follicular lymphoma? Results of a long-term follow-up study of patients treated at Stanford University. J Clin Oncol. 1996 Apr;14(4):1282-90. doi: 10.1200/JCO.1996.14.4.1282. — View Citation
Sehn LH, Chua N, Mayer J, Dueck G, Trneny M, Bouabdallah K, Fowler N, Delwail V, Press O, Salles G, Gribben J, Lennard A, Lugtenburg PJ, Dimier N, Wassner-Fritsch E, Fingerle-Rowson G, Cheson BD. Obinutuzumab plus bendamustine versus bendamustine monotherapy in patients with rituximab-refractory indolent non-Hodgkin lymphoma (GADOLIN): a randomised, controlled, open-label, multicentre, phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1081-1093. doi: 10.1016/S1470-2045(16)30097-3. Epub 2016 Jun 23. — View Citation
Trotman J, Fournier M, Lamy T, Seymour JF, Sonet A, Janikova A, Shpilberg O, Gyan E, Tilly H, Estell J, Forsyth C, Decaudin D, Fabiani B, Gabarre J, Salles B, Van Den Neste E, Canioni D, Garin E, Fulham M, Vander Borght T, Salles G. Positron emission tomography-computed tomography (PET-CT) after induction therapy is highly predictive of patient outcome in follicular lymphoma: analysis of PET-CT in a subset of PRIMA trial participants. J Clin Oncol. 2011 Aug 10;29(23):3194-200. doi: 10.1200/JCO.2011.35.0736. Epub 2011 Jul 11. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Rate of metabolic complete remission (CR) | rate of metabolic complete remission (CR) after low-dose involved site radiotherapy in combination with Obinutuzumab in patients with initially remaining PET positive lymphoma | week 18 | |
| Secondary | Rate of morphologic complete remission (CR) | rate of morphologic complete remission (CR) after low-dose involved site radiotherapy in combination with Obinutuzumab in patients with initially remaining lymphoma | week 7, week 18, month 6 | |
| Secondary | Progression free survival (PFS) | PFS of all patients | 2 years | |
| Secondary | Toxicity | Common Toxicity Criteria (CTC) Toxicity | Start until month 30 | |
| Secondary | Overall survival (OS) | OS of all patients | 2 years | |
| Secondary | Relapse rate | Relapse rate of all patients | start until month 30 | |
| Secondary | Quality of life (QoL) EORTC QLQ-C30 | QoL according EORTC QLQ-C30 | Initially, week 18, month 12, month 24 | |
| Secondary | Minimal residual disease (MRD) response | Minimal residual disease | initially, week 18, month 6, month 12, month 18, month 24 | |
| Secondary | Relapse pattern | Relapse pattern (e.g. out-field or in-field) of all relapses | start until month 30 | |
| Secondary | Quality of life (QoL) FACT-Lymph25 | QoL according FACT-Lymph25 questionnaires | Initially, week 18, month 12, month 24 |