Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma MedDRA version: 17.0 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 100000004864
Conditions
Interventions
Product Name: Ibrutinib
Product Code: JNJ-54179060
Pharmaceutical Form: Capsule
INN or Proposed INN: Ibrutinib
CAS Number: 936563-96-1
Sponsors
Janssen-Cilag International NV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Diagnosis of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that meets protocol-defined criteria •Active disease meeting at least 1 of the International Workshop on Chronic Lymphocytic Leukemia 2008 criteria for requiring treatment •Measurable nodal disease by computed tomography •Relapsed or refractory CLL or SLL following at least 1 prior line ofsystemic therapy consisting of at least 2 cycles of a chemotherapycontaining regimen •Eastern Cooperative Oncology Group Performance Status score of 0 or 1 •Hematology and biochemical values within protocol defined limits •Agrees to protocol-defined use of effective contraception •Women of childbearing potential must have negative blood or urine pregnancy test at screening 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 174 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 406
Exclusion criteria
Exclusion criteria: •Recent therapeutic interventions within 3 (chemotherapy/radiotherapy) to 10 weeks (immunotherapy) •Prior treatment with ibrutinib or other Bruton's tyrosine kinase inhibitors or prior randomization in any other clinical study evaluating ibrutinib •The presence of deletion of the short arm of chromosome 17 •Patients previously treated with a bendamustine-containing regimen who did not achieve a response or who relapsed and required treatment within 24 months of treatment with that regimen •Patients for whom the goal of therapy is tumor debulking prior to stem cell transplant •Received a hematopoietic stem cell transplant •Known central nervous system leukemia/lymphoma or Richter's transformation •Patients with uncontrolled autoimmune hemolytic anemia or autoimmune thrombocytopenia •Chronic use of corticosteroids •History of prior malignancy, except: malignancy treated with curative intent and with no known active disease present for >=3 years before randomization; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated cervical carcinoma in situ without evidence of disease •History of stroke or intracranial hemorrhage within 6 months prior to randomization; or clinically significant cardiovascular disease •Requires anticoagulation with warfarin or equivalent vitamin K antagonists or treatment with strong CYP3A4/5 inhibitors •Known history of human immunodeficiency virus or hepatitis C, or active infection with hepatitis B or C •Any uncontrolled active systemic infection or any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk •A woman who is pregnant or breast feeding, or a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to determine whether the addition of ibrutinib to BR significantly improves PFS compared with BR in subjects with relapsed or refractory CLL/SLL.;Primary end point(s): Progression-free survival;Timepoint(s) of evaluation of this end point: Up to 4 years after the last patient is randomized; Secondary Objective: The secondary objectives are: ? To evaluate the safety of ibrutinib in combination with BR ? To evaluate the ORR ? To evaluate the OS ? To evaluate the rate of MRD-negative remissions ? To evaluate improvement in hematologic parameters ? To evaluate improvement of disease-related symptoms ? To evaluate patient-reported symptoms, functional status, and wellbeing as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ)-C30, EORTC QLQ-CLL 16, EQ-5D-5L, and Functional Assessm. of Chronic Illness Therapy (FACIT)-Fatigue Scale ? To characterize the PK of ibrutinib and explore potential effect on BR PK, the potential relationships between ibrutinib metrics of exposure with relevant clinical or biomarker information ? To examine biomarkers related to BCR and compensatory signaling pathways and explore their association with resistance to ibrutinib treatment | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1/ Number of participants with adverse events 2/ Overall response rate 3/ Overall survival 4/ Rate of minimal residual disease (MRD)-negative remissions 5/ Number of participants with improvement in hematologic values 6/ Number of participants with improvement in disease-related symptoms 7/ Number of participants with improvement in patientreported outcome scores 8/ Plasma concentrations of ibrutinib 9/ Plasma concentrations of bendamustine 10/ Plasma concentrations of rituximab 11/ Number of participants with biomarkers related to B-cell receptors ; Timepoint(s) of evaluation of this end point: 1/ Up to 30 days following the last dose of study drug 2/ Up to disease progression 3/ Up to 4 years after the last patient is randomized 4-7/ Up to disease progression 8-9/ Up to Day 2, Cycle 6 10/ Up to Day 1, Cycle 12 11/ End-of-treatment visit (up to Day 450) | — |
Countries
Argentina, Belgium, Brazil, Canada, Colombia, Czech Republic, France, Germany, Greece, Israel, Korea, Republic of, Mexico, Poland, Portugal, Russian Federation, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International NV
Outcome results
None listed