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

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

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

Study Overview

• Status: Terminated
• Conditions: Multiple Myeloma; Waldenstrom Macroglobulinemia
• Intervention / Treatment: Drug: oprozomib

• Study Type: Interventional
• Enrollment (Actual): 210
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States
      • Mayo Clinic Scottsdale
  • California
    • Salinas, California, United States
      • Pacific Cancer Care
  • Colorado
    • Denver, Colorado, United States
      • Colorado Blood Cancer Institute
  • Florida
    • Jacksonville, Florida, United States
      • Mayo Clinic
  • Georgia
    • Atlanta, Georgia, United States
      • Winship Cancer Institute, Emory University
  • Illinois
    • Chicago, Illinois, United States
      • University of Chicago Medical Center
    • Chicago, Illinois, United States
      • Rush University Medical Center
  • Maryland
    • Baltimore, Maryland, United States
      • University of Maryland, Greenebaum Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States
      • Dana Farber Cancer Institute
    • Boston, Massachusetts, United States
      • Mass General Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States
      • Virginia Piper Cancer Institute
    • Rochester, Minnesota, United States
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States
      • Washington University School of Medicine Division of Oncology
  • New Jersey
    • Hackensack, New Jersey, United States
      • John Theurer Cancer Center at Hackensack University
    • Morristown, New Jersey, United States
      • Hematology Oncology of Northern New Jersey
  • New York
    • Albany, New York, United States
      • New York Oncology Hematology
    • New York, New York, United States
      • Mount Sinai Medical Center
  • Tennessee
    • Nashville, Tennessee, United States
      • Sarah Cannon Research Institute / Tennessee Oncology, PLLC
  • Washington
    • Kennewick, Washington, United States
      • Columbia Basin Hematology and Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.
• History of previous clinically significant GI bleed in the last 6 months prior to first dose.
• Female patients who are pregnant or lactating.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determine the MTD (Phase 1) and ORR (Phase 2).	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).	6 weeks to 18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the duration of response (DOR)	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.	64 months
Estimate the clinical benefit response (CBR)	CBR is defined as Overall Response Rate (ORR) plus Minimal Response (MR) of oprozomib in patients with multiple myeloma (MM)	64 months
Estimate the major response for Waldenström macroglobulinemia (WM)	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)	64 months
Evaluate progression-free survival (PFS) for multiple myeloma (MM) subjects	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	64 months
Evaluate the PFS for Waldenström macroglobulinemia (WM) subjects	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	64 months
PK parameters - maximum plasma concentration (Cmax)	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	55 months
PK parameters - time of maximum plasma concentration (tmax)	PK analyses to be performed on oprozomib and its metabolite(s) concentrations in order to estimate the time to reach Cmax (tmax)	55 months
PK parameters - plasma concentration-time curve (AUC)	PK analyses to be performed on oprozomib and its metabolite(s) concentrations in order to estimate the area under the plasma concentration-time curve	55 months
Assess renal elimination of oprozomib and its metabolites (Phase 1b only)	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.	55 months
Change from Baseline in hematology laboratory results	Assess the change from baseline in hematology panel	64 months
Change from Baseline in serum chemistry results	Assess the change from baseline in serum chemistry panel	64 months
Change from Baseline in vital signs	Assess the change from baseline in vital signs including blood pressure, pulse, and temperature	64 months
Change from Baseline in weight	Assess the change from baseline in weight	64 months
Evaluate safety of oprozomib in Phase 2	Safety to be defined by incidence, nature, severity, and relatedness of adverse events (AEs), including all serious adverse events (SAEs)	Until 30 days after the end of study (64 months)
Assess the effect on transfusion/ red blood cell (RBC) growth factor requirements (Phase 2 only) for WM only	Change from Baseline (prior 1 month) transfusion/RBC growth factor requirement in frequency and volume in WM (Phase 2 only)	64 months
Assess the effect on plasmapheresis requirements (Phase 2 only) for WM only	Change from Baseline (prior 1 month) plasmapheresis requirement in frequency and volume in WM (Phase 2 only)	64 months
Assess the effect on lymphoplasmacytic cells in the bone marrow (Phase 2 only) for WM only	Change from Baseline in percent of lymphoplasmacytic cells in the bone marrow in WM (Phase 2 only)	64 months

Collaborators and Investigators

• Sponsor: Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2011
• Primary Completion (Actual): August 8, 2016
• Study Completion (Actual): August 12, 2019

Study Registration Dates

• First Submitted: August 11, 2011
• First Submitted That Met QC Criteria: August 12, 2011
• First Posted (Estimate): August 15, 2011

Study Record Updates

• Last Update Posted (Actual): November 8, 2022
• Last Update Submitted That Met QC Criteria: November 4, 2022
• Last Verified: November 1, 2022

More Information

Terms related to this study

• Keywords: multiple myeloma; waldenstrom macroglobulinemia
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Hematologic Neoplasms; Multiple Myeloma; Waldenstrom Macroglobulinemia
• Other Study ID Numbers: 2011-001