Early Stage Follicular LymphOma and RadioTherapy PLUS Anti-CD20 Antibody

NCT ID: NCT05045664

Last Updated: 2024-12-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

100 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-06

Study Completion Date

2029-12-31

Brief Summary

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The MIR study proved the effect of Rituximab in combination with a localized irradiation given in a standard dose. Together with the TROG 99.03 trial, this led to the recommendation of using this combined approach in early stage nodal follicular lymphoma. The GAZAI study is currently looking for the effect of a low dose radiotherapy of 2x2 Gy in combination with Obinutuzumab. The combination seems to show a high CR rate based on the 50% of the patients. This is in contrast to the FORT trial, which showed an inferiority of the 4 Gy dose compared to the standard dose (24 Gy) in terms of response and progression free survival.

The goal of the FORTplus trial is to prove (1) the non-inferiority of LDRT (4Gy) in a combined approach with an anti-CD20-antibody. In case of non-inferiority, a possible (2) superiority of the Obinutuzumab + LDRT should be tested against Rituximab + standard dose using the same test set.

The radiation dose can significantly be reduced to 16% of the standard dose if (1) is confirmed. Knowing the data of the FORT trial, this would have a significant influence on the treatment of the disease worldwide even if the difference in the CR rate at week 18 is not as high as currently in the historical comparison expected.

Detailed Description

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Conditions

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Early Stage Follicular Lymphoma WHO Grade 1/2 or 3a

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Controlled, open, randomised, 2 parallel groups, multi-centre, national, treatment phase III trial
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Standard

Standard dose (24 Gy) involved site radiotherapy plus Rituximab

Group Type ACTIVE_COMPARATOR

Standard

Intervention Type RADIATION

12 x 2 Gy involved site radiotherapy plus Rituximab

Standard

Intervention Type DRUG

Rituximab with 12 x 2 Gy involved site radiotherapy

Experimental

ow-dose (4 Gy) involved site radiotherapy in combination with Obinutuzumab

Group Type EXPERIMENTAL

Experimental

Intervention Type RADIATION

2 x2 Gy involved site radiotherapy plus Obinutuzumab

Experimental

Intervention Type DRUG

Obinutuzumab with 2 x2 Gy involved site radiotherapy

Interventions

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Standard

12 x 2 Gy involved site radiotherapy plus Rituximab

Intervention Type RADIATION

Experimental

2 x2 Gy involved site radiotherapy plus Obinutuzumab

Intervention Type RADIATION

Standard

Rituximab with 12 x 2 Gy involved site radiotherapy

Intervention Type DRUG

Experimental

Obinutuzumab with 2 x2 Gy involved site radiotherapy

Intervention Type DRUG

Other Intervention Names

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Rituximab Obinutuzumab

Eligibility Criteria

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Inclusion Criteria

* • Centrally reviewed CD20-positive follicular lymphoma grade 1/2 or 3a based on WHO classification (2008)

* Untreated (radiation-, chemo- or immunotherapy) nodal follicular lymphoma (including involvement of Waldeyer´s ring)
* Age: ≥18 years
* ECOG: 0-2
* Stage: clinical stage I or II (Ann Arbor classification) based on FDG-PET Staging
* 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 bone marrow capacity: ANC ≥ 1.5 x 103/ml, thrombocytes ≥ 100000 x 10 3/ml, hemoglobin ≥ 10 g/dL
* 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

Exclusion Criteria

* Extra nodal manifestation of follicular lymphoma
* 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)
* Serious disease interfering with a regular therapy according to the study protocol, e.g: congenital or acquired immune-deficiency syndromes, active infections including viral hepatitis, uncontrolled concomitant diseases including significant cardiovascular or pulmonary disease
* Severe psychiatric disease
* Pregnancy / lactation
* Known hypersensitivity against Obinutuzumab or Rituximab drugs with similar chemical structure or any other additive of the pharmaceutical formula of the study drug
* Active hepatitis B infection (inactive hepatitis B infections require additional prophylactic anti-viral medication for 1 year (e.g. Lamivudin, Entecavir, Tenofovir)
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Heidelberg University

OTHER

Sponsor Role lead

Responsible Party

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Klaus Herfarth, MD

Vice Chair, Department of Radiation Oncology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Klaus Herfarth, MD

Role: PRINCIPAL_INVESTIGATOR

Heidelberg University

Locations

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Vivantes Klinikum Berlin

Berlin, , Germany

Site Status RECRUITING

University of Essen

Essen, , Germany

Site Status RECRUITING

University of Göttingen

Göttingen, , Germany

Site Status RECRUITING

University Hospital Heidelberg

Heidelberg, , Germany

Site Status RECRUITING

Strahlentherapie KH Maria Hilf

Mönchengladbach, , Germany

Site Status RECRUITING

LMU München

Munich, , Germany

Site Status RECRUITING

Technische Universität München

Munich, , Germany

Site Status RECRUITING

Krankenhaus Barmherzige Brüder

Regensburg, , Germany

Site Status RECRUITING

University of Rostock

Rostock, , Germany

Site Status RECRUITING

Katharinen Hospital Stuttgart

Stuttgart, , Germany

Site Status RECRUITING

University of Tübingen

Tübingen, , Germany

Site Status RECRUITING

University of Ulm

Ulm, , Germany

Site Status RECRUITING

Countries

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Germany

Central Contacts

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Klaus Herfarth, MD

Role: CONTACT

Phone: +496221568202

Email: [email protected]

Facility Contacts

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Christian Scholz, MD

Role: primary

Stefan Rieken, MD

Role: primary

Klaus Herfarth, MD

Role: primary

Ursula Nestle, MD

Role: primary

Martin Dreyling, MD

Role: primary

Simon Heidegger, MD

Role: primary

Bernhard Heilmeier, MD

Role: primary

Guido Hildebrandt, MD

Role: primary

Stefan Wirths, MD

Role: primary

Christian Buske, MD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 31470902 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24572077 (View on PubMed)

Herfarth K, Borchmann P, Schnaidt S, Hohloch K, Budach V, Engelhard M, Viardot A, Engenhart-Cabillic R, Keller U, Reinartz G, Eich HT, Witzens-Harig M, Hess CF, Dorken B, Durig J, Wiegel T, Hiddemann W, Hoster E, Pott C, Dreyling M. Rituximab With Involved Field Irradiation for Early-stage Nodal Follicular Lymphoma: Results of the MIR Study. Hemasphere. 2018 Nov 30;2(6):e160. doi: 10.1097/HS9.0000000000000160. eCollection 2018 Dec.

Reference Type RESULT
PMID: 31723798 (View on PubMed)

Hoskin P, Popova B, Schofield O, Brammer C, Robinson M, Brunt AM, Madhavan K, Illidge T, Gallop-Evans E, Syndikus I, Clifton-Hadley L, Kirkwood AA. 4 Gy versus 24 Gy radiotherapy for follicular and marginal zone lymphoma (FoRT): long-term follow-up of a multicentre, randomised, phase 3, non-inferiority trial. Lancet Oncol. 2021 Mar;22(3):332-340. doi: 10.1016/S1470-2045(20)30686-0. Epub 2021 Feb 1.

Reference Type RESULT
PMID: 33539729 (View on PubMed)

Other Identifiers

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2021-000362-15

Identifier Type: -

Identifier Source: org_study_id