Back to resultsSafety and Tolerability Study of PCI-32765 Combined With Fludarabine/Cyclophosphamide/Rituximab (FCR) and Bendamustine/Rituximab (BR) in Chronic Lymphocytic Leukemia (CLL)
Primary Purpose
B-cell Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
PCI-32765
Sponsored by
About this trial
This is an interventional treatment trial for B-cell Chronic Lymphocytic Leukemia focused on measuring Lymphoma, B-Cell, Leukemia, Lymphoid, Leukemia, B-Cell, Bruton's Tyrosine Kinase
Eligibility Criteria
Inclusion Criteria:
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)
Exclusion Criteria:
- 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
Sites / Locations
- Dana Farber Cancer Center
- CLL Research and Treatment Program
- Weill Medical College of Cornell University
- University of Rochester
- Sarah Cannon Research Institute
- MD Anderson
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
PCI-32765 plus fludarabine/cyclophosphamide/rituximab (FCR)
PCI-32765 plus bendamustine/rituximab (BR)
Arm Description
Outcomes
Primary Outcome Measures
Incidence of Prolonged Hematologic Toxicity Started in Cycle 1
Secondary Outcome Measures
Incidence of Adverse Events Requiring Dose Delay or Discontinuation of Ibrutinib
Overall Incidence of Grade ≥3 Adverse Events (AEs) Per NCI CTCAE V4.0
Overall Incidence of Serious Adverse Events (SAEs)
Overall Response Rate (Complete Response [CR] + Complete Response With Incomplete Marrow Recovery [CRi] + Nodular Partial Response [nPR] + Partial Response [PR])
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.
Sustained Hematologic Improvement in Subjects With Neutropenia, Anemia, or Thrombocytopenia at Baseline
Progression Free Survival Rate at 12 Months
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01292135
Brief Title
Safety and Tolerability Study of PCI-32765 Combined With Fludarabine/Cyclophosphamide/Rituximab (FCR) and Bendamustine/Rituximab (BR) in Chronic Lymphocytic Leukemia (CLL)
Official Title
A Phase 1b, Multicenter, Open-label, Parallel-group Safety Study of a Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI 32765, in Combination With Chemotherapy in Subjects With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
July 2014
Overall Recruitment Status
Completed
Study Start Date
February 2011 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
May 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pharmacyclics LLC.
4. Oversight
Data Monitoring Committee
No
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
B-cell Chronic Lymphocytic Leukemia, Small Lymphocytic Lymphoma
Keywords
Lymphoma, B-Cell, Leukemia, Lymphoid, Leukemia, B-Cell, Bruton's Tyrosine Kinase
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PCI-32765 plus fludarabine/cyclophosphamide/rituximab (FCR)
Arm Type
Experimental
Arm Title
PCI-32765 plus bendamustine/rituximab (BR)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
PCI-32765
Intervention Description
420 mg daily
Primary Outcome Measure Information:
Title
Incidence of Prolonged Hematologic Toxicity Started in Cycle 1
Time Frame
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 Measure Information:
Title
Incidence of Adverse Events Requiring Dose Delay or Discontinuation of Ibrutinib
Time Frame
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.
Title
Overall Incidence of Grade ≥3 Adverse Events (AEs) Per NCI CTCAE V4.0
Time Frame
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.
Title
Overall Incidence of Serious Adverse Events (SAEs)
Time Frame
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.
Title
Overall Response Rate (Complete Response [CR] + Complete Response With Incomplete Marrow Recovery [CRi] + Nodular Partial Response [nPR] + Partial Response [PR])
Description
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.
Time Frame
From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.
Title
Sustained Hematologic Improvement in Subjects With Neutropenia, Anemia, or Thrombocytopenia at Baseline
Time Frame
From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months.
Title
Progression Free Survival Rate at 12 Months
Description
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.
Time Frame
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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)
Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thorsten Graef, MD
Organizational Affiliation
Pharmacyclics LLC.
Official's Role
Study Director
Facility Information:
Facility Name
Dana Farber Cancer Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
CLL Research and Treatment Program
City
New Hyde Park
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Weill Medical College of Cornell University
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Facility Name
University of Rochester
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
MD Anderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
25755291
Citation
Brown JR, Barrientos JC, Barr PM, Flinn IW, Burger JA, Tran A, Clow F, James DF, Graef T, Friedberg JW, Rai K, O'Brien S. The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia. Blood. 2015 May 7;125(19):2915-22. doi: 10.1182/blood-2014-09-585869. Epub 2015 Mar 9.
Results Reference
derived
Links:
URL
http://www.pharmacyclics.com
Description
www.pharmacyclics.com
Learn more about this trial
Safety and Tolerability Study of PCI-32765 Combined With Fludarabine/Cyclophosphamide/Rituximab (FCR) and Bendamustine/Rituximab (BR) in Chronic Lymphocytic Leukemia (CLL)
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