Safety and Tolerability Study of PCI-32765 Combined With Fludarabine/Cyclophosphamide/Rituximab (FCR) and Bendamustine/Rituximab (BR) in Chronic Lymphocytic Leukemia (CLL)
- Conditions
- Small Lymphocytic LymphomaB-cell Chronic Lymphocytic Leukemia
- Interventions
- Registration Number
- NCT01292135
- Lead Sponsor
- Pharmacyclics LLC.
- Brief Summary
The purpose of this study is to establish the safety of orally administered PCI-32765 in combination with fludarabine/cyclophosphamide/rituximab (FCR) and bendamustine/rituximab (BR) in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma(SLL).
- Detailed Description
This is a Phase 1b, open-label, parallel-group, nonrandomized, multicenter study of PCI 32765 420 mg once daily oral (PO) administration in combination with 2 different chemotherapy regimens in subjects with relapsed/refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 33
-
Histologically confirmed CLL or SLL and satisfying at least 1 of the following criteria for requiring treatment:
- Progressive splenomegaly and/or lymphadenopathy identified by physical examination or radiographic studies
- Anemia (<11 g/dL) or thrombocytopenia (<100,000/μL) due to bone marrow involvement
- Presence of unintentional weight loss > 10% over the preceding 6 months
- NCI CTCAE Grade 2 or 3 fatigue
- Fevers > 100.5° or night sweats for > 2 weeks without evidence of infection
- Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of < 6 months
-
1 to 3 prior treatment regimens for CLL/SLL
-
ECOG performance status of ≤ 1
-
≥ 18 years of age
-
Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
-
Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local subject privacy regulations)
- Any chemotherapy, therapeutic antineoplastic antibodies (not including radio- or toxin immunoconjugates), radiation therapy, or experimental antineoplastic therapy within 4 weeks of first dose of study drug
- Radio- or toxin-conjugated antibody therapy within 10 weeks of first dose of study drug
- Concomitant use of medicines known to cause QT prolongation or torsades de pointes
- Transformed lymphoma or Richter's transformation Any life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 PO, or put the study outcomes at undue risk
- Any of the following laboratory abnormalities: oAbsolute neutrophil count (ANC) < 1000 cells/mm3 (1.0 x 109/L) oPlatelet count < 50,000/mm3 (50 x 109/L) oSerum aspartate transaminase (AST/SGOT) or alanine transaminase (ALT/SGPT) ≥ 3.0 x upper limit of normal (ULN) oCreatinine > 2.0 x ULN or creatinine clearance < 40 mL/min
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description PCI-32765 plus bendamustine/rituximab (BR) PCI-32765 - PCI-32765 plus fludarabine/cyclophosphamide/rituximab (FCR) PCI-32765 -
- Primary Outcome Measures
Name Time Method Incidence of Prolonged Hematologic Toxicity Started in Cycle 1 From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months.
- Secondary Outcome Measures
Name Time Method Overall Incidence of Grade ≥3 Adverse Events (AEs) Per NCI CTCAE V4.0 From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months. Overall Incidence of Serious Adverse Events (SAEs) From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months. Overall Response Rate (Complete Response [CR] + Complete Response With Incomplete Marrow Recovery [CRi] + Nodular Partial Response [nPR] + Partial Response [PR]) From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months. Response criteria are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. response requires 50% reduction in lymph node size. Assessment of response to treatment will be done every 2 cycles for the first 6 months and then every 3 months thereafter until disease progression or prior to the administration of a new anticancer therapy and at follow-up visits.
Incidence of Adverse Events Requiring Dose Delay or Discontinuation of Ibrutinib From First day of dose to 30 days after last dose of any study medication. Participants were followed with a median follow-up time of 15.8 months. Sustained Hematologic Improvement in Subjects With Neutropenia, Anemia, or Thrombocytopenia at Baseline From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months. Progression Free Survival Rate at 12 Months From first dose of any study medication to 12 months after first dose to progressive disease or death or the last clinical assessment before receiving new anticancer therapy or loss to follow-up, whichever occured the earliest. Criteria for progression are as outlined in the IWCLL 2008 criteria (Hallek 2008) and as assessed by investigator, e.g. progression defined as a 50% increase in lymph node size.
Trial Locations
- Locations (6)
Weill Medical College of Cornell University
🇺🇸New York, New York, United States
MD Anderson
🇺🇸Houston, Texas, United States
Dana Farber Cancer Center
🇺🇸Boston, Massachusetts, United States
CLL Research and Treatment Program
🇺🇸New Hyde Park, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Sarah Cannon Research Institute
🇺🇸Nashville, Tennessee, United States