Clinical trial • Phase III • Oncology|Haematology

Obinutuzumab for Follicular lymphoma (early stage)

Phase III trial of Obinutuzumab for Follicular lymphoma (early stage).

Overview

Trial Therapeutic Area
Oncology|Haematology
Trial Disease
Follicular lymphoma (early stage)
Trial Stage
Phase III
Drug Modality
Monoclonal antibody

Key dates

Initial CTIS Submission Date
18-12-2023
First CTIS Authorization Date
25-01-2024

Trial design

Standard dose (24 Gy) involved site (IS) radiotherapy (RT) plus Rituximab versus low-dose (4 Gy) IS RT in combination with Obinutuzumab (no specific trial drug dosing schedule stated in the available CTIS data)-controlled Phase III trial across 21 sites in Germany.

Comparator
Standard dose (24 Gy) involved site (IS) radiotherapy (RT) plus Rituximab versus low-dose (4 Gy) IS RT in combination with Obinutuzumab (no specific trial drug dosing schedule stated in the available CTIS data)
Target Sample Size
130
Trial Duration For Participant
730

Eligibility

Recruits 130 Vulnerable population flag is selected (isVulnerablePopulationSelected: true). Inclusion requires written informed consent and capability to understand the trial ('Written informed consent and willingness to cooperate during the course of the trial'; 'Capability to understand the intention and the consequences of the clinical trial'). Subject information and informed consent forms are listed among documents (L1_FORTPlus_Patienteninformation _Einwilligungserklarung; L1_FORTplus_IC_adults_TC). No provisions for assent or minor consent are provided; age eligibility is ≥18 years..

Pregnancy Exclusion
Pregnancy / lactation
Vulnerable Population
Vulnerable population flag is selected (isVulnerablePopulationSelected: true). Inclusion requires written informed consent and capability to understand the trial ('Written informed consent and willingness to cooperate during the course of the trial'; 'Capability to understand the intention and the consequences of the clinical trial'). Subject information and informed consent forms are listed among documents (L1_FORTPlus_Patienteninformation _Einwilligungserklarung; L1_FORTplus_IC_adults_TC). No provisions for assent or minor consent are provided; age eligibility is ≥18 years.

Inclusion criteria

  • {"criterion_text":"-Centrally reviewed CD20-positive follicular lymphoma grade 1/2 or 3a based on WHO classification (2016)"}
  • {"criterion_text":"-Adequate contraception for men and women of childbearing age during therapy and 18 months thereafter"}
  • {"criterion_text":"-Untreated (radiation-, chemo- or immunotherapy) nodal follicular lymphoma (including involvement of Waldeyer´s ring)"}
  • {"criterion_text":"-Age: ≥18 years"}
  • {"criterion_text":"-ECOG: 0-2"}
  • {"criterion_text":"-Stage: clinical stage I or II (Ann Arbor classification) based on FDG-PET Staging"}
  • {"criterion_text":"-Risk profile: Largest diameter of the lymphoma ≤ 7 cm (sectional images)"}
  • {"criterion_text":"-Written informed consent and willingness to cooperate during the course of the trial"}
  • {"criterion_text":"-Adequate bone marrow capacity: ANC ≥ 1.5 x 103/ml, thrombocytes ≥ 100000 x 10 3/ml, hemoglobin ≥ 10 g/dL"}
  • {"criterion_text":"-Capability to understand the intention and the consequences of the clinical trial"}

Exclusion criteria

  • {"criterion_text":"-Extra nodal manifestation of follicular lymphoma"}
  • {"criterion_text":"-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)"}
  • {"criterion_text":"-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"}
  • {"criterion_text":"-Severe psychiatric disease"}
  • {"criterion_text":"-Pregnancy / lactation"}
  • {"criterion_text":"-Known hypersensitivity against Obinutuzumab or Rituximab drugs with similar chemical structure or any other additive of the pharmaceutical formula of the study drug"}
  • {"criterion_text":"-Active hepatitis B infection (inactive hepatitis B infections require additional prophylactic anti-viral medication for 1 year (e.g. Lamivudin, Entecavir, Tenofovir)"}
  • {"criterion_text":"-Participation in another interventional trial or follow-up period of a competing trial which can influence the results of this current trial"}
  • {"criterion_text":"-Creatinine > 1.5 times the upper limit of normal (ULN) (unless creatinine clearance normal), or calculated creatinine clearance < 40 L/min"}
  • {"criterion_text":"-AST or ALT > 2.5 × ULN"}
  • {"criterion_text":"-Total bilirubin ≥ 1.5 × ULN"}
  • {"criterion_text":"-INR > 1.5 × ULN"}
  • {"criterion_text":"-PTT or aPTT > 1.5 × the ULN"}

Endpoints

Primary endpoints

  • {"endpoint_text":"-Morphologic complete response (CR) in week 18 in patients with remaining macroscopic PET positive lymphoma after initial diagnostic biopsy judged by CT (centrally reviewed)","definition_or_measurement_approach":"Assessed by CT, centrally reviewed"}

Secondary endpoints

  • {"endpoint_text":"-Morphologic CR, PR, SD, PD in week 7 and month 6 in patients with initially remaining lymphoma judged by CT/MRI","definition_or_measurement_approach":"Assessed by CT/MRI"}
  • {"endpoint_text":"-Metabolic CR in week 18 in patients with initially remaining lymphoma judged by FDGPET/ CT (centrally reviewed)","definition_or_measurement_approach":"Assessed by FDG-PET/CT, centrally reviewed"}
  • {"endpoint_text":"-Progression-free survival (PFS) of each treatment arm (2 years after individual treatment start)","definition_or_measurement_approach":"Time-to-event PFS measured up to 2 years after individual treatment start"}
  • {"endpoint_text":"-PFS of patients in stage I0 after diagnostic surgery (no remaining lymphoma) treated as the experimental arm (2 years after individual treatment start)","definition_or_measurement_approach":"Time-to-event PFS for this subgroup measured up to 2 years after individual treatment start"}
  • {"endpoint_text":"-Toxicity (NCI-CTC criteria, version 5) of all patients","definition_or_measurement_approach":"Adverse events graded per NCI-CTC v5"}
  • {"endpoint_text":"-Relapse rate and pattern of recurrence of each treatment arm at all follow-up visits.","definition_or_measurement_approach":"Relapse incidence and recurrence pattern assessed at follow-up visits"}
  • {"endpoint_text":"-Overall survival (OS) of each treatment arm (2 years)","definition_or_measurement_approach":"Overall survival measured up to 2 years"}
  • {"endpoint_text":"-Quality of life according EORTC QLQ C30 and FACT-Lym questionnaires at inclusion and in week 18, month 12, and 24 (each treatment arm)","definition_or_measurement_approach":"Patient-reported QoL using EORTC QLQ-C30 and FACT-Lym at specified timepoints"}

Recruitment

Planned Sample Size
130
Recruitment Window Months
89
Consent Approach
Written informed consent required from participants ('Written informed consent and willingness to cooperate during the course of the trial'). Age eligibility is ≥18 years and adult-specific informed consent documents are listed (L1_FORTPlus_Patienteninformation _Einwilligungserklarung; L1_FORTplus_IC_adults_TC). No assent procedures or minor consent described. Languages of consent not specified in the available data.

Geography

Total Number Of Sites
21
Total Number Of Participants
130

Germany

Earliest CTIS Part Ii Submission Date
17-01-2024
Latest Decision Or Authorization Date
08-05-2026
Processing Time Days
842
Number Of Sites
21
Number Of Participants
130

Sites

Site Name
Vivantes MVZ GmbH
Department Name
Haematologie und Onkologie
Contact Person Name
Christian Scholz
Contact Person Email
christianw.scholz@vivantes.de
Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Strahlentherapie und Radioonkologie
Contact Person Name
Alev Altay-Langguth
Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Medizinische Klinik III
Contact Person Name
Martin Dreyling
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Radioonkologie
Contact Person Name
Cihan Gani
Site Name
Universitaetsklinikum Tuebingen AöR
Department Name
Innere Medizin II
Contact Person Name
Stefan Wirths
Site Name
Vivantes MVZ GmbH
Department Name
RadioOnkologie
Contact Person Name
Axel Madlung
Site Name
Universitaetsklinikum Essen AöR
Department Name
Strahlentherapie
Contact Person Name
Thomas Gauler
Contact Person Email
Thomas.Gauler@uk-essen.de
Site Name
Universitaetsmedizin Goettingen
Department Name
Strahlentherapie und Radioonkologie
Contact Person Name
Stefan Rieken
Site Name
Barmherzige Brueder gemeinnuetzige Krankenhaus GmbH
Department Name
Klinik für Onkologie und Hämatologie
Contact Person Name
Bernhard Heilmeier
Site Name
Klinikum Der Landeshauptstadt Stuttgart gKAöR
Department Name
Strahlentherapie und Radioonkologie
Contact Person Name
Marc Münter
Site Name
Klinikum rechts der Isar der TU Muenchen AöR
Department Name
Radioonkologie und Strahlentherapie
Contact Person Name
Stephanie Combs
Contact Person Email
Stephanie.Combs@tum.de
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
RadioOnkologie
Contact Person Name
Klaus Herfarth
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Hämatologie
Contact Person Name
Isabelle Krämer
Site Name
Rostock University Medical Center
Department Name
Strahlentherapie
Contact Person Name
Guido Hildebrandt
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Innere Medizin II
Contact Person Name
Christian Buske
Contact Person Email
christian.buske@uni-ulm.de
Site Name
Kliniken Maria Hilf GmbH Moenchengladbach
Department Name
Klinik für Strahlentherapie
Contact Person Name
Ursula Nestle
Contact Person Email
ursula.nestle@mariahilf.de
Site Name
Klinikum rechts der Isar der TU Muenchen AöR
Department Name
Innere Medizin III
Contact Person Name
Maike Hefter
Contact Person Email
Maike.Hefter@mri.tum.de
Site Name
Universitaetsklinikum Essen AöR
Department Name
Hämatologie
Contact Person Name
Stephanie Sasse
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Strahlentherapie
Contact Person Name
Christian Schulz
Contact Person Email
Christian.Schulz@uksh.de
Site Name
Klinikum Oldenburg AöR
Department Name
Innere Medizin, Onkologie, Hämatologie
Contact Person Name
Christoph Kimmich
Contact Person Email
kimmich.christoph@klinikum-oldenburg
Site Name
University Medical Center Hamburg-Eppendorf
Department Name
Strahlentherapie und Onkologie
Contact Person Name
Cordula Petersen
Contact Person Email
cor.petersen@uke.de

Sponsor

Primary sponsor

Full Name
Universitaetsklinikum Heidelberg AöR
Organisation Type
Hospital/Clinic/Other health care facility
Country Of Registered Address
Germany

Investigational products

Investigational Product Name
Gazyvaro 1,000 mg concentrate for solution for infusion.
Active Substance
Obinutuzumab
Modality
Monoclonal antibody
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Authorisation Status
Marketing authorisation EU/1/14/937/001 (licensed)
Maximum Dose
max daily dose 1000 mg; max total dose 7000 mg
Investigational Product Name
MabThera 500 mg concentrate for solution for infusion
Active Substance
Rituximab
Modality
Monoclonal antibody
Routes Of Administration
Intravenous infusion
Route
Intravenous infusion
Authorisation Status
Marketing authorisation EU/1/98/067/002 (licensed)
Maximum Dose
max daily dose 375 mg/m2; max total dose 3000 mg/m2
Combination Treatment
Yes

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