An Open-label, Single arm, Multicenter Phase 2 Study of the Bruton’s Tyrosine Kinase Inhibitor PCI-32765 (Ibrutinib) in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma with 17p Deletion MedDRA version: 18.0 Level: PT Classification code 10003908 Term: B-cell small lymphocytic lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cys
Conditions
Interventions
Product Name: ibrutinib
Product Code: PCI-32765
Pharmaceutical Form: Capsule
INN or Proposed INN: Ibrutinib
CAS Number: 936563-96-1
Sponsors
Pharmacyclics LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Men or women, at least 18 years of age 2. Diagnosis of CLL/SLL meeting published diagnostic criteria:22 • monoclonal B cells (either kappa or lambda light chain restricted) that are clonally co-expressing at least 1 B-cell marker (CD19 or CD20) and CD5 • prolymphocytes may comprise no more than 55% of blood lymphocytes 3. Documentation of del (17p13.1) confirmed by central laboratory FISH analysis by peripheral blood sample 4. Must have relapsed or refractory disease after receiving at least 1 prior line of systemic therapy which included at least 2 cycles of chemotherapy or immunotherapy for CLL/SLL. 5. Currently has active disease meeting at least 1 of the following IWCLL criteria22 for requiring treatment: • evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin 10% within 6 months prior to screening o significant fatigue (inability to work or perform usual activities) o fevers >100.5° F or 38.0° C for 2 or more weeks prior to screening without evidence of infection o night sweats for more than 1 month prior to screening without evidence of infection 6. Measurable nodal disease by computed tomography (CT), defined as at least 1 lymph node >1.5 cm in the longest diameter in a site that has not been previously irradiated. An irradiated lesion may be assessed for measurable disease only if there has been documented progression in that lesion since radiotherapy has ended. 7. Eastern Cooperative Oncology Group performance status of 0 or 1 8. Adequate hematologic function, defined as absolute neutrophil count (ANC) =0.75 x 109/L (independent of growth factor support for at least 7 days prior to screening) and platelet count =30 x 109/L (independent of transfusion and growth factor support for at least 7 days prior to screening) 9. Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) =2.5 x upper limit of normal (ULN) 10. Total bilirubin =1.5 x ULN 11. Est
Exclusion criteria
Exclusion criteria: 1. Known involvement of the central nervous system by lymphoma or leukemia 2. History or current evidence of Richter’s transformation or prolymphocytic leukemia 3. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura, such as subjects with a declining hemoglobin level or platelet count secondary to autoimmune destruction within the 4 weeks prior to first dose of PCI-32765 or the need for daily corticosteroids =20 mg daily to control the autoimmune disease 4. Prior hematologic stem cell transplantation 20 mg prednisone (or equivalent) within 1 week prior to first dose of PCI-32765, with the exception of inhaled steroid for asthma, topical steroid use, etc. Subjects requiring steroids at daily doses >20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or white blood cell (WBC) count lowering are excluded 10. Major surgery within 4 weeks prior to treatment 11. History of prior malignancy, with the exception of the following: 12. Malignancy treated with curative intent and with no evidence of active disease present for more than 3 years prior to Screening and felt to be at low risk for recurrence by treating physician 13. Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled non-melanomatous skin cancer 14. Adequately treated cervical carcinoma in situ without current evidence of disease 15. Currently active clinically significant cardiovascular disease such as uncontrolled arrhythmia; Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to treatment 16. Inability to swallow capsules or tablets, or disease significantly affecting gastrointestinal function and/or inhibiting small intestine absorption (malabsorption syndrome, resection of the small bowel, poorly controlled inflammatory bowel disease, etc.) 17. Uncontrolled systemic infection or requirement for intravenous (IV) antibiotics 18. Known infection with human immunodeficiency virus 19. Serologic status reflecting active hepatitis B or C infection. Subjects who are hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative polymerase chain reaction (PCR) result prior to enrollment. Those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded. 20. History of stroke or intracranial hemorrhage within 6 months prior to enrollment 21. Current life-threatening illness, medical co
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study is to evaluate the efficacy of PCI-32765 in terms of ORR according to an Independent Review Committee (IRC) per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria in subjects with relapsed or refractory CLL/Small Lymphocytic Lymphoma (SLL) with 17p deletion as determined by fluorescence in situ hybridization (FISH) as determined by central laboratory analysis, who have received a minimum of 1 prior line of systemic treatment.; Secondary Objective: • To evaluate duration of response (DOR; including subjects who achieve a PR with lymphocytosis); and • To evaluate the safety and tolerability of PCI 32765. ;Primary end point(s): The primary endpoint is ORR, which is defined as the proportion of subjects in the m-ITT population who achieve a CR, CRi, nPR, or PR, per IWCLL 2008 criteria, based on IRC assessment, over the course of the study in subjects with del 17p CLL as confirmed by central laboratory analysis.; Timepoint(s) of evaluation of this end point: The primary analysis for all efficacy endpoints will be conducted at approximately 6 months after the last subject’s first dose of PCI-32765, and will be based on IRC assessment and the m-ITT population. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoint for efficacy is DOR (including subjects who achieve a PR with lymphocytosis), defined as the interval between the date of initial documentation of a response including PR with lymphocytosis, and the date of first documented evidence of progressive disease, death, or date of censoring if applicable, for responders only. Subjects who start new anticancer treatment before documentation of disease progression will be censored on the date of the last adequate disease assessment that is on or before the start date of new anticancer therapy. Responders are subjects in the m-ITT population who achieve CR, CRi, PR, or nPR based on IWCLL response criteria. Non-responders will be excluded from the analysis for DOR. ; Timepoint(s) of evaluation of this end point: The primary analysis for all efficacy endpoints will be conducted at approximately 6 months after the last subject’s first dose of PCI-32765, and will be based on IRC assessment and the m-ITT population. | — |
Countries
Australia, Belgium, Canada, Germany, Netherlands, New Zealand, Sweden, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trial information
Pharmacyclics LLC
Outcome results
None listed