Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Janssen Research & Development, LLC
Information provided by (Responsible Party):
Pharmacyclics
ClinicalTrials.gov Identifier:
NCT01478581
First received: November 18, 2011
Last updated: September 24, 2014
Last verified: September 2014

November 18, 2011
September 24, 2014
March 2012
January 2015   (final data collection date for primary outcome measure)
Efficacy as defined by clinical benefit rate [ Time Frame: Up to 24 Months ] [ Designated as safety issue: No ]
Participants will be followed until progression of disease or start of another anti-cancer treatment.
Same as current
Complete list of historical versions of study NCT01478581 on ClinicalTrials.gov Archive Site
  • To evaluate the efficacy of PCI-32765 by assessing the safety profile [ Time Frame: For 30 days after the last dose of PCI-32765 ] [ Designated as safety issue: Yes ]
    To measure the number of patients with adverse events as a measure of safety and tolerability
  • To evaluate the efficacy of PCI-32765 by assessing the drug pharmacokinetics [ Time Frame: Procedure will be performed during the first month of receiving study drug ] [ Designated as safety issue: Yes ]
    To measure the way the body absorbs, distributes and gets rid of the study drug
  • Duration of Clinical Benefit Response (DCB) [ Time Frame: Up to 24 months ] [ Designated as safety issue: No ]
    DCB is defined as the time from first observation of response to the time of disease progression.
  • To measure the number of patients 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 evaluate the efficacy of PCI-32765 in this population as assessed by the objective response rate, progression-free survival, time to progression, duration of objective response, and overall survival.
  • To measure the number of participants pharmacokinetics to assist in determining how the body responses to the study drug [ Time Frame: Procedure will be performed during the first month of receiving study drug ] [ Designated as safety issue: Yes ]
Not Provided
Not Provided
 
Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
A Multicenter Phase 2 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765, in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma

The primary objective of this study is to determine the efficacy of PCI-32765, both as a single agent and in combination with dexamethasone, in subjects with relapsed or relapsed and refractory Multiple Myeloma (MM)

Bruton's tyrosine kinase (Btk) is an enzyme that is present in hematopoietic cells other than T cells and is necessary for downstream signal transduction from various hematopoietic receptors including the B cell receptor as well as some Fc, chemokine, and adhesion receptors, and is crucial for both B cell development and osteoclastogenesis. Although down-regulated in normal plasma cells, Btk is highly expressed in the malignant cells from many myeloma patients and some cell lines. PCI 32765 is a potent and specific inhibitor of Btk currently in Phase 2 clinical trials. The current study is designed and intended to determine the effects of PCI-32765 in subjects with MM.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma
  • Drug: PCI-32765
  • Drug: Dexamethasone
  • Experimental: Cohort 1
    PCI-32765 420 mg per day
    Intervention: Drug: PCI-32765
  • Experimental: Cohort 2
    PCI-32765 560 mg per day, 40 mg dexamethasone (oral) once per week
    Interventions:
    • Drug: PCI-32765
    • Drug: Dexamethasone
  • Experimental: Cohort 3
    PCI-32765 840 mg per day
    Intervention: Drug: PCI-32765
  • Experimental: Cohort 4
    PCI-32765 840 mg per day, 40 mg dexamethasone (oral) once per week
    Interventions:
    • Drug: PCI-32765
    • Drug: Dexamethasone
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
164
July 2016
January 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Diagnosis of symptomatic MM with measurable disease, defined here as having at least one of the following:

    1. Serum monoclonal protein (M-protein) ≥0.5 g/dL as determined by serum protein electrophoresis (SPEP)
    2. Urine M-protein ≥200 mg/24 hrs
    3. Serum free light chain (FLC) assay: involved FLC level ≥10 mg/dL (≥100 mg/L) provided serum FLC ratio is abnormal
  • Relapsed or relapsed and refractory MM after receiving at least 2 but no more than 5 previous lines of therapy, 1 of which must be an immunomodulator.
  • Refractory myeloma (to most recent treatment) is defined as disease that is nonresponsive while on treatment or progressive disease within 60 days after the completion of preceding treatment. Nonresponsive disease is defined as either failure to achieve minimal response or development of progressive disease while on therapy.
  • Men and women ≥18 years of age.
  • ECOG performance status of ≤ 1.

Exclusion Criteria:

  • Subject must not have primary refractory disease defined as disease that is nonresponsive in subjects who have never achieved a minor response (MR) or better with any therapy.
  • Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome, osteosclerotic myeloma, or Crow-Fukase syndrome.
  • Plasma cell leukemia.
  • Primary amyloidosis.
  • Certain exclusions on prior therapy.
  • ANC <0.75 x 10^9/L independent of growth factor support.
  • Platelets <50 x 10^9/L) independent of transfusion support.
  • AST or ALT ≥3.0 x upper limit of normal (ULN).
  • Total bilirubin >2.5 x ULN, unless due to Gilbert's syndrome.
  • Creatinine >2.5 mg/dL.
  • Unable to swallow capsules or disease significantly affecting gastrointestinal function.
  • Requires anti-coagulation with warfarin or a vitamin K antagonist. Requires treatment with strong CYP3A4/5 inhibitors.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01478581
PCYC-1111-CA, PCI-32765
No
Pharmacyclics
Pharmacyclics
Janssen Research & Development, LLC
Study Director: Elizabeth Bilotti, MSN, MSJ, ANP-BC, RN Pharmacyclics
Pharmacyclics
September 2014

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