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

Phase 1

Terminated

• Conditions: Multiple Myeloma; Waldenstrom Macroglobulinemia
• Interventions: Drug: oprozomib

• Registration Number: NCT01416428
• Lead Sponsor: Amgen

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 available

Study Timeline

• Study First Submitted: 2011-08-11
• Study First Submitted QC: 2011-08-12
• Study First Posted: 2011-08-15
• Study Start: 2011-10-15
• Primary Completion: 2016-08-08
• Study Completion: 2019-08-12
• Disposition First Submitted: 2020-03-19
• Disposition First Submitted QC: 2020-03-19
• Disposition First Posted: 2020-03-23
• Status Verified: 2022-11
• Last Update Submitted: 2022-11-04
• Last Update Posted: 2022-11-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 210

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
QDx2 Dosing Schedule	oprozomib	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.
QDx5 Dosing Schedule	oprozomib	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.

Primary Outcome Measures

Name	Time	Method
Determine the MTD (Phase 1) and ORR (Phase 2).	6 weeks to 18 months	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).

Secondary Outcome Measures

Name	Time	Method
Evaluate the duration of response (DOR)	64 months	Duration of Response is defined as the time from first evidence of partial response (PR) or better to confirmation of disease progression or death due to any cause.
Estimate the clinical benefit response (CBR)	64 months	CBR is defined as Overall Response Rate (ORR) plus Minimal Response (MR) of oprozomib in patients with multiple myeloma (MM)
Estimate the major response for Waldenström macroglobulinemia (WM)	64 months	Major response for WM subjects is defined as Complete Response (CR) plus Very Good Partial Response (VGPR) plus Partial Response (PR). Major response to be equal or greater than (PR)
Evaluate progression-free survival (PFS) for multiple myeloma (MM) subjects	64 months	Progression-Free Survival is defined as the time from the start of treatment to disease progression or death (due to any cause), whichever comes first
Evaluate the PFS for Waldenström macroglobulinemia (WM) subjects	64 months	Progression-Free Survival is defined as the time from the start of treatment to disease progression or death (due to any cause), whichever comes first
PK parameters - maximum plasma concentration (Cmax)	55 months	PK analyses to be performed on oprozomib and its metabolite(s) concentrations in order to estimate the maximum observed drug concentration (Cmax) value after oral administration
PK parameters - time of maximum plasma concentration (tmax)	55 months	PK analyses to be performed on oprozomib and its metabolite(s) concentrations in order to estimate the time to reach Cmax (tmax)
PK parameters - plasma concentration-time curve (AUC)	55 months	PK analyses to be performed on oprozomib and its metabolite(s) concentrations in order to estimate the area under the plasma concentration-time curve
Assess renal elimination of oprozomib and its metabolites (Phase 1b only)	55 months	Urine will be collected over 24 hours to assess renal elimination of oprozomib and its metabolites following dosing on Day 1 of Cycle 1 for all patients.
Change from Baseline in hematology laboratory results	64 months	Assess the change from baseline in hematology panel
Change from Baseline in weight	64 months	Assess the change from baseline in weight
Assess the effect on transfusion/ red blood cell (RBC) growth factor requirements (Phase 2 only) for WM only	64 months	Change from Baseline (prior 1 month) transfusion/RBC growth factor requirement in frequency and volume in WM (Phase 2 only)
Evaluate safety of oprozomib in Phase 2	Until 30 days after the end of study (64 months)	Safety to be defined by incidence, nature, severity, and relatedness of adverse events (AEs), including all serious adverse events (SAEs)
Change from Baseline in serum chemistry results	64 months	Assess the change from baseline in serum chemistry panel
Change from Baseline in vital signs	64 months	Assess the change from baseline in vital signs including blood pressure, pulse, and temperature
Assess the effect on plasmapheresis requirements (Phase 2 only) for WM only	64 months	Change from Baseline (prior 1 month) plasmapheresis requirement in frequency and volume in WM (Phase 2 only)
Assess the effect on lymphoplasmacytic cells in the bone marrow (Phase 2 only) for WM only	64 months	Change from Baseline in percent of lymphoplasmacytic cells in the bone marrow in WM (Phase 2 only)

Trial Locations

Locations (18)

Mayo Clinic Scottsdale; 🇺🇸 Scottsdale, Arizona, United States

University of Chicago Medical Center; 🇺🇸 Chicago, Illinois, United States

Pacific Cancer Care; 🇺🇸 Salinas, California, United States

Winship Cancer Institute, Emory University; 🇺🇸 Atlanta, Georgia, United States

University of Maryland, Greenebaum Cancer Center; 🇺🇸 Baltimore, Maryland, United States

Mass General Hospital; 🇺🇸 Boston, Massachusetts, United States

John Theurer Cancer Center at Hackensack University; 🇺🇸 Hackensack, New Jersey, United States

Dana Farber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Virginia Piper Cancer Institute; 🇺🇸 Minneapolis, Minnesota, United States

Washington University School of Medicine Division of Oncology; 🇺🇸 Saint Louis, Missouri, United States

Hematology Oncology of Northern New Jersey; 🇺🇸 Morristown, New Jersey, United States

New York Oncology Hematology; 🇺🇸 Albany, New York, United States

Sarah Cannon Research Institute / Tennessee Oncology, PLLC; 🇺🇸 Nashville, Tennessee, United States

Mount Sinai Medical Center; 🇺🇸 New York, New York, United States

Columbia Basin Hematology and Oncology; 🇺🇸 Kennewick, Washington, United States

Mayo Clinic; 🇺🇸 Rochester, Minnesota, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Colorado Blood Cancer Institute; 🇺🇸 Denver, Colorado, United States