Trial record 1 of 1 for:    NCT01478581
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Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01478581
Recruitment Status : Active, not recruiting
First Posted : November 23, 2011
Last Update Posted : November 6, 2017
Information provided by (Responsible Party):
Pharmacyclics LLC.

Brief Summary:
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)

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: PCI-32765 Drug: Dexamethasone Phase 2

Detailed Description:
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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 92 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : March 2012
Actual Primary Completion Date : January 2017
Estimated Study Completion Date : March 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
U.S. FDA Resources

Arm Intervention/treatment
Experimental: Cohort 1
PCI-32765 420 mg per day
Drug: PCI-32765
Other Name: Ibrutinib
Experimental: Cohort 2
PCI-32765 560 mg per day, 40 mg dexamethasone (oral) once per week
Drug: PCI-32765
Other Name: Ibrutinib
Drug: Dexamethasone
Experimental: Cohort 3
PCI-32765 840 mg per day
Drug: PCI-32765
Other Name: Ibrutinib
Experimental: Cohort 4
PCI-32765 840 mg per day, 40 mg dexamethasone (oral) once per week
Drug: PCI-32765
Other Name: Ibrutinib
Drug: Dexamethasone

Primary Outcome Measures :
  1. Efficacy as defined by clinical benefit rate [ Time Frame: Up to 24 Months ]
    Participants will be followed until progression of disease or start of another anti-cancer treatment.

Secondary Outcome Measures :
  1. To evaluate the efficacy of PCI-32765 by assessing the safety profile [ Time Frame: For 30 days after the last dose of PCI-32765 ]
    To measure the number of patients with adverse events as a measure of safety and tolerability

  2. 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 ]
    To measure the way the body absorbs, distributes and gets rid of the study drug

  3. Duration of Clinical Benefit Response (DCB) [ Time Frame: Up to 24 months ]
    DCB is defined as the time from first observation of response to the time of disease progression.

Information from the National Library of Medicine

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

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.

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 identifier (NCT number): NCT01478581

United States, California
La Jolla, California, United States, 92093
United States, Maryland
Baltimore, Maryland, United States, 21287
United States, Massachusetts
Boston, Massachusetts, United States, 02215
United States, Michigan
Ann Arbor, Michigan, United States, 48109
United States, Missouri
Saint Louis, Missouri, United States, 63110
United States, New Jersey
Hackensack, New Jersey, United States, 07601
United States, New York
New York, New York, United States, 10029
New York, New York, United States, 10065
United States, Tennessee
Nashville, Tennessee, United States, 37203
United States, Texas
Dallas, Texas, United States, 75390
United States, Washington
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Pharmacyclics LLC.

Responsible Party: Pharmacyclics LLC. Identifier: NCT01478581     History of Changes
Other Study ID Numbers: PCYC-1111-CA
PCI-32765 ( Other Identifier: Sponsor )
First Posted: November 23, 2011    Key Record Dates
Last Update Posted: November 6, 2017
Last Verified: November 2017

Keywords provided by Pharmacyclics LLC.:
Multiple Myeloma
Relapsed Refractory Multiple Myeloma
Bruton's Tyrosine Kinase

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
BB 1101
Anti-Inflammatory Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors
Enzyme Inhibitors