Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma MedDRA version: 20.0 Level: PT Classification code 10003908 Term: B-cell small lymphocytic lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 20.1 Level: LLT Classification code 10008976 Term: Chronic lymphocytic leukemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: IMBRUVICA
Product Code: PCI-32765
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Ibrutinib
CAS Number: 936563-96-1
Current Sponsor code: PCI 32675 (Ibrutinib)
Other descriptive
Sponsors
Pharmacyclics LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Disease Related 1. Diagnosis of CLL/SLL that meets IWCLL diagnostic criteria (Hallek 2008) 2. Age 65 yrs and older OR if less than 65 years old, must have at least one of the following criteria: a) Cumulative Index Rating Score (CIRS) >6 b) Creatinine clearance 50 x 10 to the ninth power/L 6. Adequate hepatic and renal function defined as: a) Serum aspartate transaminase (AST) or alanine transaminase (ALT) = 2.5 x ULN. b) Estimated Creatinine Clearance =30 mL/min (Cockcroft-Gault) c) Bilirubin =1.5 x ULN (unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin) Demographic 7. Men and women =18 years of age. 8. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2. Ethics/other 9. Willingness to receive all outpatient treatment, all laboratory monitoring, and all radiological evaluations at the institution that administers study drug for the entire study 10. Ability to provide written informed consent and to understand and comply with the requirements of the study 11. Female subjects who are of non-reproductive potential (ie, post-menopausal by history - no menses for =1 year; OR history of hysterectomy; OR history of bilateral tubal ligation; OR history of bilateral oophorectomy). Female subjects of childbearing potential must have a negative serum pregnancy test upon study entry. 12. Male and female subjects who agree to use highly effective methods of birth control (eg, condoms, implants, injectables, combined oral contraceptives, some intrauterine devices [IUDs], sexual abstinence, or sterilized partner) during the period of therapy and for 90 days after the last dose of ibrutinib/chlorambucil or obinutuzumab, and at least 18 months after the last obinutuzumab dose for female subjects. 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 44 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 185
Exclusion criteria
Exclusion criteria: 1. Any prior chemotherapy, radiotherapy, small molecule inhibitors including kinase inhibitors, and/or monoclonal antibody used for treatment of CLL or SLL 2. Evidence of central nervous system (CNS) involvement with primary disease of CLL/SLL 3. History of other malignancies, except: a) Malignancy treated with curative intent and with no known active disease present for =3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician. b) Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease. c) Adequately treated carcinoma in situ without evidence of disease. 4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura, such as those subjects with a declining hemoglobin level or platelet count secondary to autoimmune destruction within the 4 weeks prior to first dose of study drug, or the need for daily prednisone =20 mg daily (or corticosteroid equivalent) to control the autoimmune disease. 5. Known or suspected history of Richter’s transformation. 6. Concurrent administration of >20 mg/day of prednisone within 7 days of randomization unless indicated for prophylaxis or management of allergic reactions (eg, contrast). 7. Known hypersensitivity to one or more study drugs. 8. Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug. 9. Any uncontrolled active systemic infection or infection requiring systemic treatment that was completed =7 days before randomization. 10. Known bleeding disorders (eg, von Willebrand’s disease) or hemophilia. 11. History of stroke or intracranial hemorrhage within 6 months prior to enrollment. 12. Known history of human immunodeficiency virus (HIV) or active with hepatitis B virus (HBV) or hepatitis C virus (HCV). Subjects who are positive for hepatitis B core antibody, hepatitis B surface antigen, or hepatitis C antibody must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded. 13. Major surgery within 4 weeks of first dose of study drug. 14. Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator’s opinion, could compromise the subject’s safety or put the study outcomes at undue risk. 15. Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization. 16. Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction. 17. Concomitant use of warfarin or other Vitamin K antagonists. 18. Requires treatment with a strong cytochrome P450 (CYP) 3A inhibitor. 19. Lactating or pregnant. 20. Unwilling or unable to participate in all required study evaluations and procedures. 21. Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of ibrutinib in combination with obinutuzumab compared to chlorambucil in combination with obinutuzumab based on the Independent Review Committee (IRC) assessment of progression-free survival (PFS) in subjects with treatment-naive chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL);Secondary Objective: To compare the treatment groups in terms of the following: Efficacy • Overall response rate (ORR) according to International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria, as assessed by the IRC • Rate of minimal residual disease (MRD)-negative responses • Overall Survival • Hematological improvement measured by platelet and hemoglobin counts • Patient-reported outcomes (PRO) as measured by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire EuroQoL Five-Dimension (EQ-5D-5L) Safety • To evaluate the safety and tolerability of ibrutinib in combination with obinutuzumab compared with chlorambucil in combination with obinutuzumab •To evaluate obinutuzumab-related infusion reactions by treatment arm;Primary end point(s): The primary endpoint of this study is progression-free survival (PFS) as assessed by IRC review, according to IWCLL 2008 criteria. PFS will be analyzed comparing the 2 treatment arms using a log-rank test. Distribution of PFS will be summarized for each treatment arm using the Kaplan-Meier estimate of median and its corresponding 95% confidence interval (CI). The estimate of the hazard ratio and its corresponding 95% CI will be computed using a Cox proportional hazards model.;Timepoint(s) of evaluation of this end point: The endpoints will be determined once there are 94 events in approximately 36 months from the first subject randomized. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Overall response rate: the chi-square test will be used to compare the two treatment arms. • Rate of MRD-negative response: the chi-square test will be used to compare the two treatment arms. • Overall survival: the two treatment arms will be summarized using Kaplan-Meier point estimates • Hematological improvement: in the subset of subjects with cytopenia(s) at baseline, the percentage of subjects with hematological improvement in the two treatment arms will be measured and compared using the chi-square test. • EQ-5D-5L: the scores for the five categorical dimensions will be used to compute a single utility score ranging representing the general health status of the subject. The change in utility score from baseline will be summarized. Methods will be detailed in SAP.;Timepoint(s) of evaluation of this end point: The endpoints will be determined once there are 94 events in approximately 36 months from the first subject randomized. | — |
Countries
Australia, Austria, Belgium, Canada, Czech Republic, France, Israel, Italy, New Zealand, Poland, Russian Federation, Spain, Sweden, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trial information
Pharmacyclics LLC
Outcome results
None listed