Back to resultsEarly Stage Follicular LymphOma and RadioTherapy PLUS Anti-CD20 Antibody (FORTplus)
Primary Purpose
Early Stage Follicular Lymphoma WHO Grade 1/2 or 3a
Status
Recruiting
Phase
Phase 3
Locations
Germany
Study Type
Interventional
Intervention
Standard
Experimental
Standard
Experimental
Sponsored by
About this trial
This is an interventional treatment trial for Early Stage Follicular Lymphoma WHO Grade 1/2 or 3a
Eligibility Criteria
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
Sites / Locations
- Vivantes Klinikum BerlinRecruiting
- University of Essen
- University of GöttingenRecruiting
- University Hospital HeidelbergRecruiting
- LMU München
- Technische Universität MünchenRecruiting
- Strahlentherapie KH Maria HilfRecruiting
- Krankenhaus Barmherzige BrüderRecruiting
- University of RostockRecruiting
- Katharinen Hospital Stuttgart
- University of TübingenRecruiting
- University of UlmRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Standard
Experimental
Arm Description
Standard dose (24 Gy) involved site radiotherapy plus Rituximab
ow-dose (4 Gy) involved site radiotherapy in combination with Obinutuzumab
Outcomes
Primary Outcome Measures
Morphologic complete response
Rate of morphologic complete response based on CT scan in patients with initially remaining lymphoma
Secondary Outcome Measures
Metabolic complete response
Rate of metabolic complete response based on FDG PET in patients with initially remaining lymphoma
Morphologic response
Morphologic CR in patients with initially remaining lymphoma
PFS
Progression-free survival (PFS) of each treatment arm
Frequency and extent of Toxicity
Toxicity (NCI-CTC criteria, version 5) of all patients
Overall survival
Overall survival (OS) of each treatment arm
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05045664
Brief Title
Early Stage Follicular LymphOma and RadioTherapy PLUS Anti-CD20 Antibody
Acronym
FORTplus
Official Title
Early Stage Follicular LymphOma and RadioTherapy PLUS Anti-CD20 Antibody
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 6, 2022 (Actual)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Heidelberg University
4. Oversight
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
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Early Stage Follicular Lymphoma WHO Grade 1/2 or 3a
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Controlled, open, randomised, 2 parallel groups, multi-centre, national, treatment phase III trial
Masking
None (Open Label)
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Standard
Arm Type
Active Comparator
Arm Description
Standard dose (24 Gy) involved site radiotherapy plus Rituximab
Arm Title
Experimental
Arm Type
Experimental
Arm Description
ow-dose (4 Gy) involved site radiotherapy in combination with Obinutuzumab
Intervention Type
Radiation
Intervention Name(s)
Standard
Intervention Description
12 x 2 Gy involved site radiotherapy plus Rituximab
Intervention Type
Radiation
Intervention Name(s)
Experimental
Intervention Description
2 x2 Gy involved site radiotherapy plus Obinutuzumab
Intervention Type
Drug
Intervention Name(s)
Standard
Other Intervention Name(s)
Rituximab
Intervention Description
Rituximab with 12 x 2 Gy involved site radiotherapy
Intervention Type
Drug
Intervention Name(s)
Experimental
Other Intervention Name(s)
Obinutuzumab
Intervention Description
Obinutuzumab with 2 x2 Gy involved site radiotherapy
Primary Outcome Measure Information:
Title
Morphologic complete response
Description
Rate of morphologic complete response based on CT scan in patients with initially remaining lymphoma
Time Frame
Week 18
Secondary Outcome Measure Information:
Title
Metabolic complete response
Description
Rate of metabolic complete response based on FDG PET in patients with initially remaining lymphoma
Time Frame
week 18
Title
Morphologic response
Description
Morphologic CR in patients with initially remaining lymphoma
Time Frame
Month 6
Title
PFS
Description
Progression-free survival (PFS) of each treatment arm
Time Frame
2 years
Title
Frequency and extent of Toxicity
Description
Toxicity (NCI-CTC criteria, version 5) of all patients
Time Frame
until month 30
Title
Overall survival
Description
Overall survival (OS) of each treatment arm
Time Frame
2 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Klaus Herfarth, MD
Phone
+496221568202
Email
klaus.herfarth@med.uni-heidelberg.de
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Klaus Herfarth, MD
Organizational Affiliation
Heidelberg University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vivantes Klinikum Berlin
City
Berlin
ZIP/Postal Code
10967
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Scholz, MD
Email
christianw.scholz@vivantes.de
Facility Name
University of Essen
City
Essen
ZIP/Postal Code
45147
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
University of Göttingen
City
Göttingen
ZIP/Postal Code
37075
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefan Rieken, MD
Email
stefan.rieken@med.uni-goettingen.de
Facility Name
University Hospital Heidelberg
City
Heidelberg
ZIP/Postal Code
69120
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Klaus Herfarth, MD
Phone
+496221568202
Email
klaus.herfarth@med.uni-heidelberg.de
First Name & Middle Initial & Last Name & Degree
Julia Meissner, MD
Facility Name
LMU München
City
Munich
ZIP/Postal Code
81377
Country
Germany
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Martin Dreyling, MD
Email
Martin.dreyling@med.uni-muenchen.de
Facility Name
Technische Universität München
City
Munich
ZIP/Postal Code
81675
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Simon Heidegger, MD
Email
Simon.heidegger@tum.de
Facility Name
Strahlentherapie KH Maria Hilf
City
Mönchengladbach
ZIP/Postal Code
41063
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ursula Nestle, MD
Phone
+49-2161-8921801
Email
Ursula.nestle@mariahilf.de
Facility Name
Krankenhaus Barmherzige Brüder
City
Regensburg
ZIP/Postal Code
93049
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bernhard Heilmeier, MD
Email
Bernhard.Heilmeier@barmherzige-regensburg.de
Facility Name
University of Rostock
City
Rostock
ZIP/Postal Code
18057
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Guido Hildebrandt, MD
Email
guido.hildebrandt@med.uni-rostock.de
Facility Name
Katharinen Hospital Stuttgart
City
Stuttgart
Country
Germany
Individual Site Status
Not yet recruiting
Facility Name
University of Tübingen
City
Tübingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Stefan Wirths, MD
Email
Stefan.Wirths@med.uni-tuebingen.de
Facility Name
University of Ulm
City
Ulm
ZIP/Postal Code
89081
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christian Buske, MD
Email
Christian.buske@uni-ulm.de
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
31470902
Citation
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.
Results Reference
background
PubMed Identifier
24572077
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.
Results Reference
background
PubMed Identifier
31723798
Citation
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.
Results Reference
result
PubMed Identifier
33539729
Citation
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.
Results Reference
result
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Early Stage Follicular LymphOma and RadioTherapy PLUS Anti-CD20 Antibody
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