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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)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pharmacyclics
ClinicalTrials.gov Identifier:
NCT01292135
First received: February 2, 2011
Last updated: July 17, 2014
Last verified: July 2014

February 2, 2011
July 17, 2014
February 2011
November 2012   (final data collection date for primary outcome measure)
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. ] [ Designated as safety issue: Yes ]
To measure the number of participants with prolonged hematologic toxicity [ Time Frame: 8 weeks from first dose ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT01292135 on ClinicalTrials.gov Archive Site
  • 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. ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: Yes ]
  • 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. ] [ Designated as safety issue: No ]
    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 [ Time Frame: From first response assessment to last response assessment. Participants were followed with a median follow-up time of 15.8 months. ] [ Designated as safety issue: No ]
  • 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. ] [ Designated as safety issue: No ]
    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.
  • To measure the number of participants with adverse events as a measure of safety and tolerability [ Time Frame: For 30 days after the last dose of PCI-32765 ] [ Designated as safety issue: Yes ]
  • To measure the number of patients who respond to treatment by measuring the increase or decrease of disease in the lymph nodes and/or blood test results [ Time Frame: Patients may remain on study until the last subject enrolled completes a maximum of 12 cycles of PCI-32765. Any subjects still receiving PCI-32765 at that time may enroll in a long-term follow-up study to continue to receive PCI-32765 capsules ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Safety and Tolerability Study of PCI-32765 Combined With Fludarabine/Cyclophosphamide/Rituximab (FCR) and Bendamustine/Rituximab (BR) in Chronic Lymphocytic Leukemia (CLL)
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

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).

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).

Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • B-cell Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
Drug: PCI-32765
420 mg daily
  • Experimental: PCI-32765 plus fludarabine/cyclophosphamide/rituximab (FCR)
    Intervention: Drug: PCI-32765
  • Experimental: PCI-32765 plus bendamustine/rituximab (BR)
    Intervention: Drug: PCI-32765
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
33
May 2013
November 2012   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01292135
PCYC-1108-CA, PCI-32765
No
Pharmacyclics
Pharmacyclics
Not Provided
Study Director: Thorsten Graef, MD Pharmacyclics
Pharmacyclics
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP