Study of the Bruton's Tyrosine Kinase Inhibitor in Subjects With Relapsed or Relapsed and Refractory Multiple Myeloma
This study is currently recruiting participants.
Verified May 2013 by Pharmacyclics
Sponsor:
Pharmacyclics
Information provided by (Responsible Party):
Pharmacyclics
ClinicalTrials.gov Identifier:
NCT01478581
First received: November 18, 2011
Last updated: May 6, 2013
Last verified: May 2013
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Purpose
This study will evaluate the safety and preliminary efficacy of PCI-32765 in relapsed or relapsed and refractory Multiple Myeloma
| 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:
Drug Information available for:
Dexamethasone
Tyrosine
Dexamethasone acetate
Dexamethasone sodium phosphate
U.S. FDA Resources
Further study details as provided by Pharmacyclics:
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: | January 2015 (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.
Optional Sub-Study:
Subjects entering the main study will be eligible to participate in an exploratory sub-study to investigate possible mechanisms of treatment sensitivity and resistance. Bone marrow specimens will be collected at three timepoints.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| 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:
- Serum monoclonal protein (M-protein) ≥0.5 g/dL as determined by serum protein electrophoresis (SPEP)
- Urine M-protein ≥200 mg/24 hrs
- 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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT01478581
Contacts
| Contact: Mandy Parson | 408-215-3003 | mparson@pcyc.com |
| Contact: Efrat Matkovitch | 408-215-3020 | ematkovitch@pcyc.com |
Locations
| United States, Illinois | |
| University of Chicago Medical Center | Recruiting |
| Chicago, Illinois, United States, 60637 | |
| Contact: Kathryn McDonnell 773-702-1835 kmcdonnell@bsd.uchicago.edu | |
| Principal Investigator: Andrzej Jakubowiak, MD | |
| United States, Maryland | |
| Johns Hopkins University | Recruiting |
| Baltimore, Maryland, United States, 21287 | |
| Contact: Emily Lederer 410-614-6551 epalmis1@jhmi.edu | |
| Principal Investigator: Carol Ann Huff, MD | |
| United States, Massachusetts | |
| Dana Farber Cancer Institute | Recruiting |
| Boston, Massachusetts, United States, 02215 | |
| Contact: Heather Goddard 617-632-3655 Heather_Goddard@dfci.harvard.edu | |
| Principal Investigator: Paul Richardson, MD | |
| United States, Michigan | |
| University of Michigan | Recruiting |
| Ann Arbor, Michigan, United States, 48109 | |
| Contact: Jessica Lantz 734-936-6936 jessicap@med.umich.edu | |
| Principal Investigator: Daniel Lebovic, MD | |
| United States, Missouri | |
| Washington University School of Medicine | Recruiting |
| St. Louis, Missouri, United States, 63114 | |
| Contact: Brett Ramsey 314-747-2844 baramsey@dom.wustl.edu | |
| Principal Investigator: Ravi Vij, MD | |
| United States, New Jersey | |
| Hackensack University Medical Center | Recruiting |
| Hackensack, New Jersey, United States, 07601 | |
| Contact: Laura Guerrero 551-996-5232 lguerrero@hackensackumc.org | |
| Contact: Laura Raucci 551-996-5683 LRaucci@HackensackUMC.org | |
| Principal Investigator: David Siegel, MD | |
| United States, New York | |
| Memorial Sloan Kettering Cancer Center | Recruiting |
| New York, New York, United States, 10065 | |
| Contact: Nailah Cummings 646-449-1337 cummingn@mskcc.org | |
| Principal Investigator: Nikoletta Lendvai, MD | |
| United States, Tennessee | |
| Sarah Cannon Research Institute | Recruiting |
| Nashville, Tennessee, United States, 37203 | |
| Contact: Wanda Smith 615-329-7487 wanda.smith@scresearch.net | |
| Principal Investigator: Jesus Berdeja, MD | |
Sponsors and Collaborators
Pharmacyclics
More Information
No publications provided
| Responsible Party: | Pharmacyclics |
| ClinicalTrials.gov Identifier: | NCT01478581 History of Changes |
| Other Study ID Numbers: | PCYC-1111-CA, PCI-32765 |
| Study First Received: | November 18, 2011 |
| Last Updated: | May 6, 2013 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board |
Keywords provided by Pharmacyclics:
|
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 Therapeutic Uses Pharmacologic Actions Antiemetics Autonomic Agents Peripheral Nervous System Agents Physiological Effects of Drugs Central Nervous System Agents Gastrointestinal Agents Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |
ClinicalTrials.gov processed this record on June 17, 2013