Rituximab with or without Ibrutinib for untreated patients with advanced follicular lymphoma in need of therapy.

Phase 1

Conditions: Follicular Lymphoma (FL), advanced disease in need of therapy
MedDRA version: 20.0Level: HLGTClassification code 10025320Term: Lymphomas non-Hodgkin's B-cellSystem Organ Class: 10005329 - Blood and lymphatic system disorders
Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

Registration Number: EUCTR2015-001487-19-AT

Lead Sponsor: Swiss Group For Clinical Cancer Research (SAKK)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 190

Inclusion Criteria

6.1.1 Written informed consent according to ICH/GCP guidelines
6.1.2 Histologically confirmed FL CD20+; grade 1, 2, 3a; stage III+IV; stage II not suitable for radiotherapy; all FLIPI
6.1.3 Tumor specimens (slides or block) available for pathological review
6.1.4 In need of systemic therapy (at least one of the following indications must be fulfilled):
? Symptomatic disease
? Bulky disease (= 6 cm)
? Steady, clinically significant progression over at least 3 months of any tumor lesion
? B-symptoms (weight loss > 10% in 6 months, drenching night sweats, fever > 38°C not due to infection)
? Anemia (hemoglobin < 100 g/L) or thrombocytopenia (platelets 50-100 x 109/L) due to lymphoma
6.1.5 At least one two-dimensionally measurable lesion with a longest diameter (LDi) = 15 mm or a measurable extranodal lesion with a LDi > 10 mm in contrast-enhanced 18F-FDG PET/CT* scan
6.1.6 At least one FDG-avid tumor lesion in contrast-enhanced 18F-FDG PET/CT* scan
6.1.7 Age 18-85 years
6.1.8 WHO performance status 0-2
6.1.9 Adequate bone marrow function:
? Absolute neutrophil count (ANC) > 1.0 x 109/L independent of growth factor support
? Platelets = 100 x 109/L or = 50 x 109/L if bone marrow involvement independent of transfusion support in either situation
6.1.10 Adequate hepatic function:
? Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 3 x upper limit of normal (ULN)
? Total bilirubin = 1.5 x ULN unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin
6.1.11 Adequate renal function:
? Serum creatinine = 2 x ULN and corrected calculated creatinine clearance = 40 mL/min/1.73m2.
6.1.12 Women of childbearing potential have a negative serum (beta-human chorionic gonadotropin [?-hCG]) or urine pregnancy test at Screening.
6.1.13 Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females and males, these restrictions apply for 12 months after the last dose of study drug.
6.1.14 Patient compliance and geographic proximity allow proper staging and follow-up.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 76
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 114

Exclusion Criteria

6.2.1 Tumor bulk requiring fast response
6.2.2 Known central nervous system lymphoma
6.2.3 Previous systemic FL therapies
6.2.4 Major surgery 4 weeks prior to randomization
6.2.5 Previous or concomitant malignancy diagnosed within 3 years with the exception of adequately treated cervical carcinoma in situ or localized non-melanoma skin cancer
6.2.6 History of stroke or intracranial hemorrhage within 6 months prior to randomization
6.2.7 Clinically significant cardiovascular diseases such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
6.2.8 Known history of human immunodeficiency virus (HIV) or active Hepatitis C Virus or active Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (i.v.) antibiotics
6.2.9 Concomitant diseases that require anticoagulation with warfarin or equivalent vitamin K antagonists (eg. phenprocoumon), factor Xa inhibitors (e.g. rivaroxaban, apixaban), direct thrombin inhibitors (e.g. dabigatran) or platelet inhibitors/antiplatelet agents
6.2.10 Concomitant diseases that require treatment with strong or moderate CYP3A inhibitors, including St. John's wort (see http://medicine.iupui.edu and also chapter 9)
6.2.11 Any concomitant drugs contraindicated for use with the trial drugs according to the approved product information or known hypersensitivity to the trial drugs Ibrutinib/Placebo and Rituximab or to any of their components (including placebo)
6.2.12 Concurrent treatment with other experimental drugs or other anticancer therapy, treatment in a clinical trial within 30 days prior to trial entry
6.2.13 Vaccinated with live, attenuated vaccines 4 weeks prior to randomization
6.2.14 Any life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator’s opinion, could compromise the subject’s safety, interfere with the absorption or metabolism of Ibrutinib capsules, or put the study outcomes at undue risk
6.2.15 Psychiatric disorder precluding understanding information of trial related topics, giving informed consent or interfering with compliance for oral drug intake
6.2.16 Women who are pregnant or breastfeeding
6.2.17 Patients regularly taking corticosteroids during the last 4 weeks, unless administered at a dose equivalent to Prednisone = 15 mg/day for indications other than lymphoma or lymphoma-related symptoms

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The objective of this trial is to study the activity and the safety of the 1st line treatment with Ibrutinib in combination with Rituximab for patients with advanced follicular lymphoma in need of therapy. <br>Primary endpoint: CR at 24 months determined by PET/CT scan by the IRR panel;Secondary Objective: Secondary endpoints:<br>Complete Response (CR) at 30 months determined by PET/CT scan by the IRR panel<br>MRD evaluation<br>Overall response (OR) at 24 weeks<br>Duration of complete response<br>Progression-free survival (PFS)<br>Event-free survival (EFS)<br>Time to next anti-lymphoma therapy (TTNT)<br>Overall survival (OS)<br>Adverse Events (AEs);Primary end point(s): Complete Response (CR) at 24 months determined by PET/CT scan by the IRR panel<br>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.;Timepoint(s) of evaluation of this end point: 24 months

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Secondary endpoints:<br>? CR at 30 months determined by PET/CT scan by the IRR panel<br>? MRD evaluation<br>? Overall response (OR) at 24 weeks<br>? Duration of complete response (DUR)<br>? Progression-free survival (PFS)<br>? Event-free survival (EFS)<br>? Time to next anti-lymphoma therapy (TTNT)<br>? Overall survival (OS)<br>? Adverse Events (AEs)<br>? Exploratory endpoints;Timepoint(s) of evaluation of this end point: ? CR: at 30 months <br>? MRD evaluation: baseline and week 106<br>? Overall response (OR): at 24 weeks<br>? Duration of complete response: at 12 or 24 weeks or thereafter<br>? Progression-free survival (PFS): at 12 or 24 weeks or thereafter<br>? Event-free survival (EFS): 12, 24 or 52 weeks <br>? Time to next anti-lymphoma therapy (TTNT): at 12 or 24 weeks or thereafter<br>? Overall survival (OS) from randomization until death. <br> Adverse events (AEs) throughout treatment phase <br> Exploratory endpoints<br><br>

Related Trials