Open-label Study of the Safety and Activity of Oprozomib in Patients With Hematologic Malignancies

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Onyx Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier:
NCT01416428
First received: August 11, 2011
Last updated: June 27, 2014
Last verified: June 2014
  Purpose

The purpose of this study is to determine the maximum tolerated dose (MTD), activity, and safety of oprozomib in patients with hematologic malignancies.


Condition Intervention Phase
Multiple Myeloma
Waldenstrom Macroglobulinemia
Drug: oprozomib
Phase 1
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: Phase 1b/2, Multicenter, Open-label Study of the Safety and Activity of Oprozomib in Patients With Hematologic Malignancies

Resource links provided by NLM:


Further study details as provided by Onyx Pharmaceuticals:

Primary Outcome Measures:
  • Determine the MTD (Phase 1) and ORR (Phase 2). [ Time Frame: 6 weeks to 18 months ] [ Designated as safety issue: Yes ]

    Phase 1- Determine Maximum Tolerated Dose (MTD) with 3 + 3 Dose Escalation Cohorts in patients hematologic malignancies.

    Phase 2- The Phase 2 portion of this trial will enroll patients with Multiple Myeloma (MM) and Waldenstrom Macroglobulinemia (WM) into separate arms to assess activity of oprozomib in these patient groups. The purpose of the Phase 2 portion of the study is to estimate the best ORR (for each group separately).



Estimated Enrollment: 349
Study Start Date: September 2011
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: QDx2 Dosing Schedule

QDx2 is defined as patients receiving Oprozomib Tablets once daily on Days 1, 2, 8, and 9 of the 14-day cycle.

The schedule will be evaluated in Phase 1 for MTD in patients with hematologic malignancies, and will also be evaluated in Phase 2 for ORR in patients with MM and WM.

Drug: oprozomib
Patients enrolled will receive Oprozomib Tablets once daily either on Days 1-5 (QDx5 schedule) or on Days 1, 2, 8, and 9 (QDx2 weekly schedule) of the 14-day treatment cycle.
Experimental: QDx5 Dosing Schedule

QDx5 is defined as patients receiving Oprozomib Tablets once daily on Days 1 to 5 of the 14-day cycle.

The schedule will be evaluated in Phase 1 for MTD in patients with hematologic malignancies, and will also be evaluated in Phase 2 for ORR in patients with MM and WM.

Drug: oprozomib
Patients enrolled will receive Oprozomib Tablets once daily either on Days 1-5 (QDx5 schedule) or on Days 1, 2, 8, and 9 (QDx2 weekly schedule) of the 14-day treatment cycle.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

Phase 1b

  • Histologically confirmed diagnosis of a hematologic malignancy, excluding patients with acute leukemia or MDS.
  • Relapsed after standard therapy for their malignancy and considered to be an appropriate candidate for a Phase 1 clinical study by their treating physician.

Phase 2

  • Multiple myeloma with measurable disease
  • Waldenström macroglobulinemia with symptomatic relapse
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.

Ethical/Other

  • Patients must sign a written informed consent form in accordance with federal, local, and institutional guidelines.
  • Female patients of childbearing potential must have a negative serum or urine pregnancy test and agree to use effective contraception. Male patients must use an effective barrier method of contraception.

EXCLUSION CRITERIA:

  • Chemotherapy with approved or investigational anticancer therapeutics, including steroid therapy intended to treat underlying malignancy, within 3 weeks prior to first dose or 6 weeks for antibody therapy.
  • Radiation therapy within 3 weeks prior to first dose. Radioimmunotherapy within 8 weeks prior to first dose. Localized radiation therapy within 1 week prior to first dose.
  • Immunotherapy within 3 weeks prior to first dose (except for antibody therapy, where 6 weeks is required).
  • Prior stem cell transplant (SCT) therapy (autologous SCT within the prior 8 weeks; allogeneic SCT within the prior 16 weeks). Patients with prior allogeneic SCT should not have evidence of moderate-to-severe graft-vs-host disease (GvHD; as defined in Filipovich 2005).
  • Evidence of central nervous system (CNS) lymphoma.
  • Prior treatment with carfilzomib unless in the phase 2.
  • Major surgery within 3 weeks prior to first dose.
  • Symptomatic Congestive heart failure, ischemia, conduction abnormalities, or myocardial infarction within 6 months.
  • Acute active infection requiring systemic antibiotics, antivirals, or antifungals.
  • Known or suspected human immunodeficiency virus (HIV) infection or patients who are HIV seropositive.
  • Active hepatitis A, B, or C infection.
  • Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose.
  • Patients with pleural effusions requiring routine thoracentesis or ascites requiring routine paracentesis.
  • Female patients who are pregnant or lactating.
  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: NCT01416428

Contacts
Contact: Onyx Medical Information 877-ONYX-121 (877-669-9121) medinfo@onyx.com

Locations
United States, Arizona
Oncology Research Associates Recruiting
Scottsdale, Arizona, United States, 85258
Contact       medinfo@onyx.com   
United States, Florida
Mayo Clinic Recruiting
Jacksonville, Florida, United States
United States, Georgia
Winship Cancer Institute, Emory University Recruiting
Atlanta, Georgia, United States, 30322
United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States
Rush University Medical Center Recruiting
Chicago, Illinois, United States
United States, Maryland
University of Maryland, Greenebaum Cancer Center Recruiting
Baltimore, Maryland, United States, 21201
Contact       medinfo@onyx.com   
United States, Massachusetts
Dana Farber Cancer Institute Recruiting
Boston, Massachusetts, United States, 02215
Contact       medinfo@onyx.com   
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States
United States, Missouri
Washington University School of Medicine Division of Oncology Recruiting
St. Louis, Missouri, United States, 63110
United States, New Jersey
John Theurer Cancer Center at Hackensack University Recruiting
Hackensack, New Jersey, United States, 07601
United States, New York
Mount Sinai Medical Center Recruiting
New York, New York, United States, 10029
Contact       medinfo@onyx.com   
United States, Tennessee
Tennessee Oncology, PLLC Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
South Texas Accelerated Research Therapeutics Recruiting
San Antonio, Texas, United States, 78229
Contact       medinfo@onyx.com   
Sponsors and Collaborators
Onyx Therapeutics, Inc.
Investigators
Study Director: Study Director, MD Onyx Therapeutics, Inc.
  More Information

No publications provided

Responsible Party: Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier: NCT01416428     History of Changes
Other Study ID Numbers: 2011-001
Study First Received: August 11, 2011
Last Updated: June 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Onyx Pharmaceuticals:
multiple myeloma
waldenstrom macroglobulinemia

Additional relevant MeSH terms:
Waldenstrom Macroglobulinemia
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
Lymphatic Diseases

ClinicalTrials.gov processed this record on September 18, 2014