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

This study is currently recruiting participants.

Verified April 2013 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: April 11, 2013

Last verified: April 2013

History of Changes

Tracking Information

First Received Date ^ICMJE

August 11, 2011

Last Updated Date

April 11, 2013

Start Date ^ICMJE

September 2011

Estimated Primary Completion Date

May 2014 (final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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).

Original Primary Outcome Measures ^ICMJE

Determine the MTD of ONX 0912 in patients with hematological malignancies [ Time Frame: 6 weeks to 18 months ] [ Designated as safety issue: Yes ]

The purpose of the Phase 1b Escalation portion of the study is for dose-escalation of ONX 0912 to the Maximum Tolerated Dose (MTD) in patients with hematological malignancies. A minimum of 3 patients will be entered within each dose cohort, to be expanded to 6 patients if Dose Limiting Toxicities (DLTs) are observed.It is estimated that approximately 42 patients will be required for determining the MTD. This is based on an estimate that up to 7 cohorts will be required to determine the MTD, and a maximum of 6 patients will be required in each of the 7 cohorts.

Change History

Complete list of historical versions of study NCT01416428 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures ^ICMJE

Not Provided

Original Secondary Outcome Measures ^ICMJE

Estimate the best Overall Response Rate (ORR) [ Time Frame: 6 weeks to 36 months ] [ Designated as safety issue: No ]

The Phase 2 portion of this trial will enroll patients with Multiple Myeloma (MM), Waldenstrom's Macroglobulinemia (WM), and Mantle Cell Lymphoma (MCL) into separate arms to assess activity of ONX 0912 in these patient groups. The purpose of the Phase 2 portion of the study is to estimate the best ORR (for each group separately).

Current Other Outcome Measures ^ICMJE

Not Provided

Original Other Outcome Measures ^ICMJE

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

Phase 1b/2, Multicenter, Open-label Study of the Safety and Activity of Oprozomib in Patients With Hematologic Malignancies

Brief Summary

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

Detailed Description

Not Provided

Study Type ^ICMJE

Interventional

Study Phase

Phase 1
Phase 2

Study Design ^ICMJE

Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Condition ^ICMJE

Multiple Myeloma
Waldenstrom Macroglobulinemia

Intervention ^ICMJE

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.

Study Arm (s)

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.

Intervention: Drug: oprozomib
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.

Intervention: Drug: oprozomib

Publications *

Not Provided

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Recruiting

Estimated Enrollment ^ICMJE

263

Estimated Completion Date

December 2014

Estimated Primary Completion Date

May 2014 (final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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.
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.

Gender

Both

Ages

18 Years and older

Accepts Healthy Volunteers

Contacts ^ICMJE

Contact: Onyx Medical Information

877-ONYX-121 (877-669-9121)

medinfo@onyx.com

Location Countries ^ICMJE

United States

Administrative Information

NCT Number ^ICMJE

NCT01416428

Other Study ID Numbers ^ICMJE

2011-001

Has Data Monitoring Committee

Yes

Responsible Party

Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )

Study Sponsor ^ICMJE

Onyx Therapeutics, Inc.

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:

Study Director, MD

Onyx Therapeutics, Inc.

Information Provided By

Onyx Pharmaceuticals

Verification Date

April 2013

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

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