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Stage II Grade 1 Follicular LymphomaPhase 2GAZAINCT03341520

Gazyvaro and Low Dose Radiotherapy in Early Stage Follicular Lymphoma

A Phase 2 study testing Obinutuzumab Injection [Gazyva] and Low dose radiation Therapy (LDRT) in people with Stage II Grade 1 Follicular Lymphoma and Stage II Grade 2 Follicular Lymphoma, run by Heidelberg University at 12 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Obinutuzumab Injection [Gazyva] and Low dose radiation Therapy (LDRT)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
89 participants
Where
12 sitesGermany
Study dates
24 Apr 2018to 14 Mar 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
Show all 11Show fewer
  • 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)

Who cannot join

  • 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
Show all 12Show fewer
  • 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 locations and contacts

12 sites in 1 country.

12 sites in 1 country

Germany12 sites

  • Vivantes Klinikum

    Berlin

  • University of Cologne

    Cologne, 50924

  • University of Essen

    Essen, 45122

  • University of Frankfurt

    Frankfurt, 60590

  • University of Heidelberg

    Heidelberg, 69120

  • Klinikum Kempten

    Kempten

  • Site Marburg

    Marburg

  • LMU

    Munich, 81377

  • TU

    Munich, 81675

  • University of Muenster

    Münster

  • University of Tuebingen

    Tübingen, Baden-Wurttemberg

  • University of Ulm

    Ulm, 89081

Other trials in Germany

About this study

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

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.

Read the detailed description

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.

Being tested
Obinutuzumab Injection [Gazyva], Low dose radiation Therapy (LDRT)
Medical subject headings
Lymphoma, Follicular

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Obinutuzumab Injection [Gazyva]Drug

    Also called Gazyvaro

    7x 1000mg flat dose

  • Low dose radiation Therapy (LDRT)Radiation

    2 x 2 Gy

Study groups in NCT03341520
Study groupRoleWhat they receive
interventional armExperimentalObinutuzumab 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
Receives: Drug: Obinutuzumab Injection [Gazyva]; Radiation: Low dose radiation Therapy (LDRT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: week 18

Secondary outcomes (9)

  1. 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

    Measured: week 7, week 18, month 6

  2. Progression free survival (PFS)

    PFS of all patients

    Measured: 2 years

  3. Toxicity

    Common Toxicity Criteria (CTC) Toxicity

    Measured: Start until month 30

  4. Overall survival (OS)

    OS of all patients

    Measured: 2 years

  5. Relapse rate

    Relapse rate of all patients

    Measured: start until month 30

  6. Quality of life (QoL) EORTC QLQ-C30

    QoL according EORTC QLQ-C30

    Measured: Initially, week 18, month 12, month 24

  7. Minimal residual disease (MRD) response

    Minimal residual disease

    Measured: initially, week 18, month 6, month 12, month 18, month 24

  8. Relapse pattern

    Relapse pattern (e.g. out-field or in-field) of all relapses

    Measured: start until month 30

  9. Quality of life (QoL) FACT-Lymph25

    QoL according FACT-Lymph25 questionnaires

    Measured: Initially, week 18, month 12, month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Nov 2017
  2. Study start24 Apr 2018
  3. Primary completion11 Nov 2021
  4. Study completion14 Mar 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
Open, non-controlled, national multi-center phase II trial
Masking
None (open label)
Enrolment
89 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03341520
Sponsor's protocol ID
2016-002059-89
Other IDs
2016
Acronym
GAZAI
Status last verified
Feb 2025
First submitted
6 Nov 2017
Last updated
17 Apr 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • 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.

    PubMed 8648385

  • 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.

    PubMed 12829665

  • 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.

    PubMed 24572077

  • 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.

    PubMed 21747087

  • 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.

    PubMed 27345636

  • Konig L, Dreyling M, Durig J, Engelhard M, Hohloch K, Viardot A, Witzens-Harig M, Kieser M, Klapper W, Pott C, Herfarth K. Therapy of nodal Follicular Lymphoma (WHO grade 1/2) in clinical stage I/II using response adapted Involved Site Radiotherapy in combination with Obinutuzumab (Gazyvaro) - GAZAI Trial (GAZyvaro and response adapted Involved-site Radiotherapy): a study protocol for a single-arm, non-randomized, open, national, multi-center phase II trial. Trials. 2019 Aug 30;20(1):544. doi: 10.1186/s13063-019-3614-y.

    PubMed 31470902

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Obinutuzumab Injection [Gazyva] and Low dose radiation Therapy (LDRT) in people with Stage II Grade 1 Follicular Lymphoma and Stage II Grade 2 Follicular Lymphoma, run by Heidelberg University at 12 sites in Germany.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Rate of metabolic complete remission (CR) (time frame: week 18). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03341520, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2026.

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