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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:
Information provided by (Responsible Party):
Pharmacyclics LLC.
ClinicalTrials.gov Identifier:
NCT01478581
First received: November 18, 2011
Last updated: January 22, 2016
Last verified: September 2015
  Purpose
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 Intervention Phase
Multiple Myeloma
Drug: PCI-32765
Drug: Dexamethasone
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Pharmacyclics LLC.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 164
Study Start Date: March 2012
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
PCI-32765 420 mg per day
Drug: PCI-32765
Experimental: Cohort 2
PCI-32765 560 mg per day, 40 mg dexamethasone (oral) once per week
Drug: PCI-32765 Drug: Dexamethasone
Experimental: Cohort 3
PCI-32765 840 mg per day
Drug: PCI-32765
Experimental: Cohort 4
PCI-32765 840 mg per day, 40 mg dexamethasone (oral) once per week
Drug: PCI-32765 Drug: Dexamethasone

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01478581

Locations
United States, California
SITE-13
La Jolla, California, United States, 92093
United States, Maryland
SITE-5
Baltimore, Maryland, United States, 21287
United States, Massachusetts
SITE-4
Boston, Massachusetts, United States, 02215
United States, Michigan
SITE-8
Ann Arbor, Michigan, United States, 48109
United States, Missouri
SITE-2
St. Louis, Missouri, United States, 63110
United States, New Jersey
SITE-6
Hackensack, New Jersey, United States, 07601
United States, New York
SITE-10
New York, New York, United States, 10029
SITE-3
New York, New York, United States, 10065
United States, Tennessee
SITE-1
Nashville, Tennessee, United States, 37203
United States, Texas
SITE-11
Dallas, Texas, United States, 75390
United States, Washington
SITE-9
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Pharmacyclics LLC.
Investigators
Study Director: Elizabeth Bilotti, MSN,MSJ,RN Pharmacyclics LLC an AbbVie Company
  More Information

Responsible Party: Pharmacyclics LLC.
ClinicalTrials.gov Identifier: NCT01478581     History of Changes
Other Study ID Numbers: PCYC-1111-CA  PCI-32765 
Study First Received: November 18, 2011
Last Updated: January 22, 2016
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Pharmacyclics LLC.:
PCI-32765
Multiple Myeloma
Relapsed Refractory Multiple Myeloma
Bruton's Tyrosine Kinase

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors

ClinicalTrials.gov processed this record on December 02, 2016