FORTplus: Early Stage Follicular LymphOma and RadioTherapy PLUS Anti-CD20 Antibody

• Sponsor: Heidelberg University (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT05045664
• Collaborator: (none)
• Enrollment: 100
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 89.9
• Patients Per Site Per Month: 1.1

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Early Stage Follicular Lymphoma WHO Grade 1/2 or 3a	Radiation: Standard; Radiation: Experimental; Drug: Standard; Drug: Experimental	Phase 3

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Controlled, open, randomised, 2 parallel groups, multi-centre, national, treatment phase III trialControlled, open, randomised, 2 parallel groups, multi-centre, national, treatment phase III trial
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Early Stage Follicular LymphOma and RadioTherapy PLUS Anti-CD20 Antibody
• Actual Study Start Date: Jul 6, 2022
• Anticipated Primary Completion Date: Dec 31, 2026
• Anticipated Study Completion Date: Dec 31, 2029

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Standard Standard dose (24 Gy) involved site radiotherapy plus Rituximab	Radiation: Standard; 12 x 2 Gy involved site radiotherapy plus Rituximab; Drug: Standard; Rituximab with 12 x 2 Gy involved site radiotherapy; Other Names: Rituximab
Experimental: Experimental ow-dose (4 Gy) involved site radiotherapy in combination with Obinutuzumab	Radiation: Experimental; 2 x2 Gy involved site radiotherapy plus Obinutuzumab; Drug: Experimental; Obinutuzumab with 2 x2 Gy involved site radiotherapy; Other Names: Obinutuzumab

Outcome Measures

Primary Outcome Measures

1. Morphologic complete response [Week 18]

   Rate of morphologic complete response based on CT scan in patients with initially remaining lymphoma

Secondary Outcome Measures

1. Metabolic complete response [week 18]

   Rate of metabolic complete response based on FDG PET in patients with initially remaining lymphoma

2. Morphologic response [Month 6]

   Morphologic CR in patients with initially remaining lymphoma

3. PFS [2 years]

   Progression-free survival (PFS) of each treatment arm

4. Frequency and extent of Toxicity [until month 30]

   Toxicity (NCI-CTC criteria, version 5) of all patients

5. Overall survival [2 years]

   Overall survival (OS) of each treatment arm

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital Heidelberg	Heidelberg		Germany	69120

Sponsors and Collaborators

• Heidelberg University

Investigators

• Principal Investigator: Klaus Herfarth, MD, Heidelberg University

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• König L, Dreyling M, Dürig 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.

• Responsible Party: Klaus Herfarth, MD, Vice Chair, Department of Radiation Oncology, Heidelberg University
• ClinicalTrials.gov Identifier: NCT05045664
• Other Study ID Numbers: 2021-000362-15
• First Posted: Sep 16, 2021
• Last Update Posted: Jul 12, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• 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
• Additional relevant MeSH terms: Lymphoma; Lymphoma, Follicular; Obinutuzumab

Study Results

No Results Posted as of Jul 12, 2022