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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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ClinicalTrials.gov Identifier: NCT01292135
Recruitment Status : Completed
First Posted : February 9, 2011
Results First Posted : July 24, 2014
Last Update Posted : July 24, 2014
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics LLC.

Study Description
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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).

Condition or disease Intervention/treatment Phase
B-cell Chronic Lymphocytic Leukemia Small Lymphocytic Lymphoma Drug: PCI-32765 Phase 1

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).
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : February 2011
Actual Primary Completion Date : November 2012
Actual Study Completion Date : May 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Ibrutinib

Arms and Interventions
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Arm Intervention/treatment
Experimental: PCI-32765 plus fludarabine/cyclophosphamide/rituximab (FCR) Drug: PCI-32765
420 mg daily
Experimental: PCI-32765 plus bendamustine/rituximab (BR) Drug: PCI-32765
420 mg daily


Outcome Measures
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Primary Outcome Measures :
  1. 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 Measures :
  1. 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. ]
  2. 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. ]
  3. 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. ]
  4. Overall Response Rate (Complete Response [CR] + Complete Response With Incomplete Marrow Recovery [CRi] + Nodular Partial Response [nPR] + Partial Response [PR]) [ Time Frame: 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.

  5. 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. ]
  6. Progression Free Survival Rate at 12 Months [ 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. ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. 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
  2. 1 to 3 prior treatment regimens for CLL/SLL
  3. ECOG performance status of ≤ 1
  4. ≥ 18 years of age
  5. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty
  6. 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:

  1. 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
  2. Radio- or toxin-conjugated antibody therapy within 10 weeks of first dose of study drug
  3. Concomitant use of medicines known to cause QT prolongation or torsades de pointes
  4. 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
  5. 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01292135


Locations
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United States, Massachusetts
Dana Farber Cancer Center
Boston, Massachusetts, United States, 02115
United States, New York
CLL Research and Treatment Program
New Hyde Park, New York, United States, 11042
Weill Medical College of Cornell University
New York, New York, United States, 10065
University of Rochester
Rochester, New York, United States, 14642
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson
Houston, Texas, United States, 77030
Sponsors and Collaborators
Pharmacyclics LLC.
Investigators
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Study Director: Thorsten Graef, MD Pharmacyclics LLC.
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT01292135    
Other Study ID Numbers: PCYC-1108-CA
PCI-32765 ( Other Identifier: Pharmacyclics )
First Posted: February 9, 2011    Key Record Dates
Results First Posted: July 24, 2014
Last Update Posted: July 24, 2014
Last Verified: July 2014
Keywords provided by Pharmacyclics LLC.:
Lymphoma, B-Cell
Leukemia, Lymphoid
Leukemia, B-Cell
Bruton's Tyrosine Kinase
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
 Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell