An Open-label Extension Study in Patients 65 Years or Older with Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Who Participated in Study PCYC-1115-CA (Ibrutinib versus Chlorambucil)

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 272

Inclusion Criteria

1. Randomized in the parent study, PCYC-1115-CA
2. Informed consent for Study PCYC-1116-CA
3. IRC-confirmed PD in the parent study or closure of the parent study

To receive second-line ibrutinib, patients must meet all of the following criteria:
1. IRC-confirmed disease progression in the parent study (PCYC-1115-CA), or for patients who did not progress in the parent study, investigator-determined disease progression in the extension study (PCYC 1116-CA)
2. Received at least 3 cycles of chlorambucil therapy
3. Documented, protocol-defined reason for chlorambucil discontinuation:
• No evidence of response in radiographically assessed disease parameters at Cycle 5 compared to baseline; no further response (defined as failure to reach at least a PR, or a plateau of response with no further improvement of disease parameters) after at least 6 cycles; could not tolerate treatment (a situation defined by the recurrence of toxicity of at least Grade 3 despite appropriate dose reductions and optimal symptomatic management); or maximum treatment of 12 cycles with chlorambucil
4. Demonstrates continuation of adequate organ function, performance status, and other criteria, as follows:
• Eastern Cooperative Oncology Group (ECOG) status of 0-2
• Adequate hematologic function, defined as absolute neutrophil count (ANC) = 0.75 x109/L (independent of growth factor support in the preceding 7 days) and platelet count = 30 x 109/L (independent of transfusion or growth factor support in the preceding 7 days)
• Adequate hepatic function, defined as serum aspartate transaminase (AST) and alanine transaminase (ALT) < 2.5 x upper limit of normal (ULN), and total bilirubin = 1.5 xULN (unless due to Gilbert's syndrome)
• Adequate renal function, defined as an estimated glomerular filtration rate = 30 mL/min using the Cockcroft-Gault equation
• Patients must have recovered from acute toxicities due to prior chemotherapy, radiotherapy, investigational drugs or experimental treatments (non-hematologic toxicities have resolved to a NCI CTCAE [version 4.0] Grade of =2) prior to receiving next line ibrutinib on this study
5. Meets at least 1 of the International Workshop on Chronic Lymphocytic Leukemia (IWCLL) criteria for active disease requiring treatment (Hallek 2008):
• Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin < 10 g/dL), and/or thrombocytopenia (platelets < 100,000/µL)
• Massive (= 6 cm below the left costal margin), progressive, or symptomatic splenomegaly
• Massive nodes (at least 10 cm longest diameter), progressive, or symptomatic lymphadenopathy
• Progressive lymphocytosis with an increase of more than 50% over a 2 month period or a lymphocyte doubling time (LDT) of < 6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In patients with initial blood lymphocyte counts of < 30,000/µL, LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (eg, infections) should be excluded.
• Autoimmune hemolytic anemia and/or immune thrombocytopenia (see definitions below) that is poorly responsive to corticosteroids or other standard therapy
(Definitions: Autoimmune hemolytic anemia is defined by at least 1 marker of hemolysis [indirect bilirubin above th

Exclusion Criteria

To receive second-line ibrutinib, patients must meet NONE of the following criteria:
1. Disease progression involving the central nervous system (CNS) or transformation to another histology
2. Intervening chemotherapy, immunotherapy, or investigational agent specifically to treat CLL if administered before date of IRC confirmed
progressive disease
3. In the 4 weeks before dosing, radiation therapy, major surgery, or receipt of an investigational drug
4. Requirement for treatment with a strong CYP3A inhibitor
5. Uncontrolled systemic infection or requirement for intravenous (IV) antibiotics
6. Noncompliance on the parent study

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Related Trials