Gazyvaro and Low Dose Radiotherapy in Early Stage Follicular Lymphoma (GAZAI)

November 29, 2023 updated by: Klaus Herfarth, MD, Heidelberg University

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

89

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany
        • Vivantes Klinikum
      • Cologne, Germany, 50924
        • University of Cologne
      • Essen, Germany, 45122
        • University of Essen
      • Frankfurt, Germany, 60590
        • University of Frankfurt
      • Heidelberg, Germany, 69120
        • University of Heidelberg
      • Kempten, Germany
        • Klinikum Kempten
      • Marburg, Germany
        • Site Marburg
      • Munich, Germany, 81377
        • LMU
      • Munich, Germany, 81675
        • TU
      • Münster, Germany
        • University of Muenster
      • Ulm, Germany, 89081
        • University of Ulm
    • Baden-Wuerttemberg
      • Tuebingen, Baden-Wuerttemberg, Germany
        • University of Tuebingen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • Gazyvaro
Radiation: Low dose radiation Therapy (LDRT)
2 x 2 Gy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
week 18

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
week 7, week 18, month 6
Progression free survival (PFS)
Time Frame: 2 years
PFS of all patients
2 years
Toxicity
Time Frame: Start until month 30
Common Toxicity Criteria (CTC) Toxicity
Start until month 30
Overall survival (OS)
Time Frame: 2 years
OS of all patients
2 years
Relapse rate
Time Frame: start until month 30
Relapse rate of all patients
start until month 30
Quality of life (QoL) EORTC QLQ-C30
Time Frame: Initially, week 18, month 12, month 24
QoL according EORTC QLQ-C30
Initially, week 18, month 12, month 24
Minimal residual disease (MRD) response
Time Frame: initially, week 18, month 6, month 12, month 18, month 24
Minimal residual disease
initially, week 18, month 6, month 12, month 18, month 24
Relapse pattern
Time Frame: start until month 30
Relapse pattern (e.g. out-field or in-field) of all relapses
start until month 30
Quality of life (QoL) FACT-Lymph25
Time Frame: Initially, week 18, month 12, month 24
QoL according FACT-Lymph25 questionnaires
Initially, week 18, month 12, month 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Heidelberg University

Collaborators

Roche Pharma AG

Investigators

  • Study Chair: Klaus Herfarth, MD, Radiation Therapy, University Hospital of Heidelberg ,Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 24, 2018

Primary Completion (Actual)

November 11, 2021

Study Completion (Estimated)

May 1, 2024

Study Registration Dates

First Submitted

November 6, 2017

First Submitted That Met QC Criteria

November 12, 2017

First Posted (Actual)

November 14, 2017

Study Record Updates

Last Update Posted (Actual)

November 30, 2023

Last Update Submitted That Met QC Criteria

November 29, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2016-002059-89

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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