An Open-label Extension Study in Patients 65 Years or Older withChronic Lymphocytic Leukemia (CLL) or Small LymphocyticLymphoma (SLL) Who Participated in Study PCYC-1115-CA(PCI-32765 versus Chlorambucil)

• Conditions: Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL); MedDRA version: 14.1Level: LLTClassification code 10060669Term: B-cell chronic lymphocytic leukemia/prolymphocytic leukemia/small lymphocytic lymphomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2012-003968-44-ES
• Lead Sponsor: Pharmacyclics, Incorporated

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-12-21
• Last Update Posted: 4 March 2013

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• 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 PCI-32765, 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. Considered to be high-risk for failure to standard chemotherapy due to IRC-confirmed progressive disease within 12 months of last chlorambucil dose (standard treatment of these patients includes an investigational agent in a clinical trial); OR considered to be high risk for failure to standard chemotherapy due to acquired 17p deletion or p53 mutation
5. 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
? Adequate renal function, defined as an estimated glomerular filtration rate >= 30 mL/min using the Cockcroft-Gault equation
6. 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/microL)
? 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/microL, 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 hemo

Exclusion Criteria

To receive second-line PCI-32765, 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
3. More than a 12-month interval between discontinuation of chlorambucil and planned start of PCI-32765
4. In the 4 weeks before dosing, radiation therapy, major surgery, or receipt of an investigational drug
5. Requirement for treatment with a strong CYP3A4/5 inhibitor
6. Uncontrolled systemic infection or requirement for intravenous (IV) antibiotics
7. Noncompliance on the parent study

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified