A Phase 2 interventional study of Ibrutinib and Rituximab in Follicular Lymphoma, sponsored by Swiss Group for Clinical Cancer Research. Terminated at 42 sites in 6 countries. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2024-03-13.
Sponsored by Swiss Group for Clinical Cancer Research · Phase 2, Interventional, and Treatment
Follicular lymphomas FL has been traditionally approached either by an initial watch and wait policy in the asymptomatic patient, or with single agent treatments with the purpose of maintaining a good quality of life for a prolonged time.The combination of rituximab and ibrutinib has been tested in clinical trials and appeared to be well tolerated and active. Since ibrutinib seems to achieve better results when administered for prolonged time as shown in CLL, the investigators have chosen to compare its combination with rituximab to the prolonged rituximab-only schedule that was already shown to be very active in the SAKK 35/03 trial.
The aim of the study is to investigate the efficacy, safety and tolerability of the treatment combination of Ibrutinib and Rituximab for patients with advanced follicular lymphoma in need of therapy.
Follicular lymphomas FL has been traditionally approached either by an initial watch and wait policy in the asymptomatic patient, or with single agent treatments with the purpose of maintaining a good quality of life for a prolonged time.
During the last decades, treatment strategies have changed due to the continuous development and introduction of novel therapeutic approaches (including immunotherapy with interferon-alpha or monoclonal antibodies, the combination of immunotherapy with chemotherapy, and radioimmunotherapy with radiolabeled monoclonal antibodies).
For the asymptomatic patients with advanced-stage, but low tumor burden, randomized studies have confirmed that systemic treatment can be deferred until development of symptoms or organ failure (which generally occurred within 2-3 years from diagnosis) without any overall survival impairment and a watchful waiting policy has long remained a widely accepted approach.
For the symptomatic patients with more advanced tumor burden, in need of initial treatment, the combination of rituximab and chemotherapy, possibly followed by rituximab maintenance became a new standard in many countries.
In this setting of a chemotherapy-free strategy, the clinical study of rituximab combinations with other immunotherapies or with novel targeted agents is obvious relevant. Promising results have also been reported with the combination of rituximab and lenalidomide.
The combination of rituximab and ibrutinib has been tested in clinical trials and appeared to be well tolerated and active. Since ibrutinib seems to achieve better results when administered for prolonged time as shown in CLL, the investigators have chosen to compare its combination with rituximab to the prolonged rituximab-only schedule that was already shown to be very active in the SAKK 35/03 trial.
SAKK has a long tradition in treatment of FL patients with chemotherapy-free treatment based on rituximab. This is a worldwide special situation, which creates cooperation between important partners for clinical trials in this area.
The aim of the study is to investigate the efficacy, safety and tolerability of the treatment combination of Ibrutinib and Rituximab for patients with advanced follicular lymphoma in need of therapy.
5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's enrollment of 190 is above the median of 40 across 4,508 interventional studies indexed under Lymphoma.
Browse Lymphoma studies →Swiss Group for Clinical Cancer Research is the lead sponsor of 107 studies on the registry; none are open to participants now.
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In need of systemic therapy (at least one of the following indications must be fulfilled):
Adequate bone marrow function:
Adequate hepatic function:
Adequate renal function:
Exclusion Criteria:
Ibrutinib capsules for 24 months (104 weeks) daily (always at the same time) in a dose of 560 mg (4 x 140 mg capsules)
Drug: Ibrutinib · Drug: Rituximab
Placebo as comparator for 24 months (4 capsules daily always at the same time)
Drug: Rituximab
Patients will be instructed by the Investigator to take the amount of 560 mg Ibrutinib/Placebo (4 x 140 mg capsules) orally once daily with a glass of water at approximately the same time every day.
Also known as: Imbruvica®
Rituximab 375 mg/m2 has to be administered i.v. for the first four (4) infusions in all patients. After i.v. administration of Rituximab for the induction therapy, the administration mode can be changed to s.c. (1400 mg) in the maintenance phase dependent on the local standard of care.
Also known as: MabThera®
CR at 24 months determined by PET/CT scan by the IRR panel
The evaluation of CR is outlined according to Cheson Criteria.. Any assessment within a window of week 102 to week 118 (inclusive) will be considered as the 24 months response assessment for determining the CR status. In addition, the CR status will be determined as follows for these specific cases:
Time frame: at 24 months
CR at 30 months determined by PET/CT scan by the IRR panel
Time frame: at 30 months
MRD evaluation
MRD evaluation will be performed using real-time PCR (polymerase chain reaction) based methods in peripheral blood and bone marrow at baseline and week 106. The proportion of patients achieving MRD negativity will be calculated for each time point of interest.
Time frame: baseline and week 106
Overall response (OR)
OR is defined as either: * the disappearance of all evidence of disease (CR) * the regression of measurable disease with no new sites (PR)
Time frame: at 24 weeks
Duration of complete response (DUR)
The duration of CR will be calculated from when the criteria for CR are met, until documentation of relapse thereafter. Only patients with a CR will be included in this analysis.
Time frame: at 12 or 24 weeks or thereafter
Progression-free survival (PFS) (PFS)
PFS will be calculated from randomization until the first event of interest: * disease progression or relapse according to criteria of Cheson et al. 2014 * death from any cause
Time frame: at 12 or 24 weeks or thereafter
Event-free survival (EFS)
Event-free survival (time to treatment failure) will be calculated from randomization to premature discontinuation of trial treatment for any reason (e.g., insufficient response at first or second restaging at 12 or 24 weeks or at the third assessment at 52 weeks, disease progression, toxicity, patient preference, initiation of new treatment without documented progression, secondary malignancy or death).
Time frame: 12, 24 or 52 weeks
Time to next anti-lymphoma therapy (TTNT)
This will be calculated from randomization until the start of the first off-trial anti-lymphoma treatment. Patients not receiving any off-trial anti-lymphoma treatment will be censored at the last follow-up visit.
Time frame: at 12 or 24 weeks or thereafter
Adverse Events (AEs)
AEs will be evaluated using the NCI CTCAE v4.0
Time frame: record throughout treatment phase (until 30 days after last drug administration)
Plan to share: No
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This study is terminated, as verified in Mar 2024. You cannot join it, but the record below documents what was studied.
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Swiss Group for Clinical Cancer Research