Gazyvaro and Low Dose Radiotherapy in Early Stage Follicular Lymphoma (GAZAI)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03341520|
Recruitment Status : Recruiting
First Posted : November 14, 2017
Last Update Posted : July 8, 2019
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.
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.
Efficacy and safety of a response adapted radiation dose treatment schedule.
|Condition or disease||Intervention/treatment||Phase|
|Stage II Grade 1 Follicular Lymphoma Stage II Grade 2 Follicular Lymphoma Stage I Follicular Lymphoma Grade 1 Stage II Follicular Lymphoma Grade 2||Drug: Obinutuzumab Injection [Gazyva] Radiation: Low dose radiation Therapy (LDRT)||Phase 2|
Extended field or total nodal irradiation had been the gold standard for early stage follicular lymphoma for a long time in Germany. An involved field (IF) irradiation has been favored due to the toxicity of large field irradiation in other countries (e.g. USA). However, smaller irradiation fields have been accompanied with an increased risk of recurrence. A combination of involved field irradiation with the anti-CD20 antibody Rituximab (MIR trial) has led to similar efficacy results compared to the large field irradiation but with markedly reduced side effects.
Haas et al. showed in a prospective trial, that a low dose radiation therapy (LDRT) can lead to a complete remission in up to 60% in follicular lymphoma. This is presumed to result from immune modulatory effects induced by LDRT. The effectiveness of LDRT could also be demonstrated in another prospective, randomized British trial (FORT trial: 2 x2 Gy vs. 12 x 2 Gy) with a CR rate of 40% after 2 x 2 Gy (60% after 12 x 2 Gy). Currently, it is unknown, which patients need a higher radiation dose and which not.
A metabolic complete remission (CR) is an important prognostic marker for progression-free survival. According to the results of the PRIMA trial, CR is a very strong predictive parameter if the CR is established using FDG-PET.
In the present GAZAI trial, patients with early stage nodular follicular lymphoma will be treated in a combined approach of immunotherapy with an anti-CD20 antibody and small field (involved site) irradiation as in the MIR trial. In GAZAI, the fully humanized anti-CD20 antibody Obinutuzumab (GAZYVARO) will be used, which showed a high efficacy in combination with bendamustin in patients with follicular lymphoma refractory to Rituximab (GADOLIN trial). In addition, the radiation dose will be limited to 2 x2 Gy in responding patients. A dose build-up to a total of 40 Gy (dose in the MIR trial) will be performed in case of failure to achieve a complete CR based on a FDG-PET in week 18.
Primary endpoint of the trial is the rate of CR (based on FDG-PET/CT) after Obinutuzumab and 2x2 Gy IS radiotherapy in week 18. Secondary endpoints are the morphological CR rate in week 7, week 18 and month 6, the PFS, the toxicity, the recurrence rate, the recurrence pattern, overall survival and quality of life.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||93 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Open, non-controlled, national multi-center phase II trial|
|Masking:||None (Open Label)|
|Official 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|
|Actual Study Start Date :||April 24, 2018|
|Estimated Primary Completion Date :||June 2021|
|Estimated Study Completion Date :||September 2023|
Experimental: interventional arm
Obinutuzumab Injection [Gazyva] 1000mg flat i.v. on week 1, 2, 3, 4, 8, 12, 16; Low dose radiation Therapy (LDRT) involved site 2 x 2 Gy in week 9
Drug: Obinutuzumab Injection [Gazyva]
7x 1000mg flat dose
Other Name: Gazyvaro
Radiation: Low dose radiation Therapy (LDRT)
2 x 2 Gy
- Rate of metabolic complete remission (CR) [ Time Frame: week 18 ]rate of metabolic complete remission (CR) after low-dose involved site radiotherapy in combination with Obinutuzumab in patients with initially remaining PET positive lymphoma
- Rate of morphologic complete remission (CR) [ Time Frame: week 7, week 18, month 6 ]rate of morphologic complete remission (CR) after low-dose involved site radiotherapy in combination with Obinutuzumab in patients with initially remaining lymphoma
- Progression free survival (PFS) [ Time Frame: 2 years ]PFS of all patients
- Toxicity [ Time Frame: Start until month 30 ]Common Toxicity Criteria (CTC) Toxicity
- Overall survival (OS) [ Time Frame: 2 years ]OS of all patients
- Relapse rate [ Time Frame: start until month 30 ]Relapse rate of all patients
- Quality of life (QoL) EORTC QLQ-C30 [ Time Frame: Initially, week 18, month 12, month 24 ]QoL according EORTC QLQ-C30
- Minimal residual disease (MRD) response [ Time Frame: initially, week 18, month 6, month 12, month 18, month 24 ]Minimal residual disease
- Relapse pattern [ Time Frame: start until month 30 ]Relapse pattern (e.g. out-field or in-field) of all relapses
- Quality of life (QoL) FACT-Lymph25 [ Time Frame: Initially, week 18, month 12, month 24 ]QoL according FACT-Lymph25 questionnaires
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03341520
|Contact: Klaus Herfarth, MD||+49 6221 email@example.com|
|University of Tuebingen||Recruiting|
|Tuebingen, Baden-Wuerttemberg, Germany|
|Contact: Martin Soekler, MD firstname.lastname@example.org|
|Contact: Christian Scholz, MD Christiane.email@example.com|
|University of Cologne||Recruiting|
|Cologne, Germany, 50924|
|Contact: Kai Hübel, MD firstname.lastname@example.org|
|University of Essen||Recruiting|
|Essen, Germany, 45122|
|Contact: Jan Duerig, MD email@example.com|
|University of Heidelberg||Recruiting|
|Heidelberg, Germany, 69120|
|Contact: Klaus Herfarth, MD firstname.lastname@example.org|
|Contact: Johann Schmier, MD email@example.com|
|Contact: Christian Langer, MD Christian.langer@klinikum-Kempten.de|
|Contact: Florian Sterzing, MD F.sterzing@strahlentherapie-Kempten.de|
|Munich, Germany, 81377|
|Contact: Martin Dreyling, MD firstname.lastname@example.org|
|Munich, Germany, 81675|
|Contact: Ulrich Keller, MD email@example.com|
|University of Muenster||Recruiting|
|Contact: Georg Lenz, MD Georg.firstname.lastname@example.org|
|Contact: Hans Eich, MD Hans.email@example.com|
|University of Ulm||Recruiting|
|Ulm, Germany, 89081|
|Contact: Christian Buske, MD firstname.lastname@example.org|
|Contact: Andreas Viardot, MD email@example.com|
|Study Chair:||Klaus Herfarth, MD||Radiation Therapy, University Hospital of Heidelberg ,Germany|