Back to resultsOpen-label Study of the Safety and Activity of Oprozomib in Patients With Hematologic Malignancies
Primary Purpose
Multiple Myeloma, Waldenstrom Macroglobulinemia
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
oprozomib
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Myeloma focused on measuring multiple myeloma, waldenstrom macroglobulinemia
Eligibility 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.
- History of previous clinically significant GI bleed in the last 6 months prior to first dose.
- Female patients who are pregnant or lactating.
Sites / Locations
- Mayo Clinic Scottsdale
- Pacific Cancer Care
- Colorado Blood Cancer Institute
- Mayo Clinic
- Winship Cancer Institute, Emory University
- Rush University Medical Center
- University of Chicago Medical Center
- University of Maryland, Greenebaum Cancer Center
- Dana Farber Cancer Institute
- Mass General Hospital
- Virginia Piper Cancer Institute
- Mayo Clinic
- Washington University School of Medicine Division of Oncology
- John Theurer Cancer Center at Hackensack University
- Hematology Oncology of Northern New Jersey
- New York Oncology Hematology
- Mount Sinai Medical Center
- Sarah Cannon Research Institute / Tennessee Oncology, PLLC
- Columbia Basin Hematology and Oncology
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
QDx2 Dosing Schedule
QDx5 Dosing Schedule
Arm Description
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 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.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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)
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)
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
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
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
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)
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
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.
Change from Baseline in hematology laboratory results
Assess the change from baseline in hematology panel
Change from Baseline in serum chemistry results
Assess the change from baseline in serum chemistry panel
Change from Baseline in vital signs
Assess the change from baseline in vital signs including blood pressure, pulse, and temperature
Change from Baseline in weight
Assess the change from baseline in weight
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)
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)
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)
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)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01416428
Brief Title
Open-label Study of the Safety and Activity of Oprozomib in Patients With Hematologic Malignancies
Official Title
Phase 1b/2, Multicenter, Open-label Study of the Safety and Activity of Oprozomib in Patients With Hematologic Malignancies
Study Type
Interventional
2. Study Status
Record Verification Date
November 2022
Overall Recruitment Status
Terminated
Why Stopped
A program evaluation identified that the safety profile and pharmacokinetic (PK) characteristics of the formulation used in all oprozomib studies required further optimization and thus enrollment in 2011-001 was halted.
Study Start Date
October 15, 2011 (Actual)
Primary Completion Date
August 8, 2016 (Actual)
Study Completion Date
August 12, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Myeloma, Waldenstrom Macroglobulinemia
Keywords
multiple myeloma, waldenstrom macroglobulinemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
210 (Actual)
8. Arms, Groups, and Interventions
Arm Title
QDx2 Dosing Schedule
Arm Type
Experimental
Arm Description
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.
Arm Title
QDx5 Dosing Schedule
Arm Type
Experimental
Arm Description
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 Type
Drug
Intervention Name(s)
oprozomib
Intervention Description
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.
Primary Outcome Measure Information:
Title
Determine the MTD (Phase 1) and ORR (Phase 2).
Description
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).
Time Frame
6 weeks to 18 months
Secondary Outcome Measure Information:
Title
Evaluate the duration of response (DOR)
Description
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.
Time Frame
64 months
Title
Estimate the clinical benefit response (CBR)
Description
CBR is defined as Overall Response Rate (ORR) plus Minimal Response (MR) of oprozomib in patients with multiple myeloma (MM)
Time Frame
64 months
Title
Estimate the major response for Waldenström macroglobulinemia (WM)
Description
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)
Time Frame
64 months
Title
Evaluate progression-free survival (PFS) for multiple myeloma (MM) subjects
Description
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
Time Frame
64 months
Title
Evaluate the PFS for Waldenström macroglobulinemia (WM) subjects
Description
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
Time Frame
64 months
Title
PK parameters - maximum plasma concentration (Cmax)
Description
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
Time Frame
55 months
Title
PK parameters - time of maximum plasma concentration (tmax)
Description
PK analyses to be performed on oprozomib and its metabolite(s) concentrations in order to estimate the time to reach Cmax (tmax)
Time Frame
55 months
Title
PK parameters - plasma concentration-time curve (AUC)
Description
PK analyses to be performed on oprozomib and its metabolite(s) concentrations in order to estimate the area under the plasma concentration-time curve
Time Frame
55 months
Title
Assess renal elimination of oprozomib and its metabolites (Phase 1b only)
Description
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.
Time Frame
55 months
Title
Change from Baseline in hematology laboratory results
Description
Assess the change from baseline in hematology panel
Time Frame
64 months
Title
Change from Baseline in serum chemistry results
Description
Assess the change from baseline in serum chemistry panel
Time Frame
64 months
Title
Change from Baseline in vital signs
Description
Assess the change from baseline in vital signs including blood pressure, pulse, and temperature
Time Frame
64 months
Title
Change from Baseline in weight
Description
Assess the change from baseline in weight
Time Frame
64 months
Title
Evaluate safety of oprozomib in Phase 2
Description
Safety to be defined by incidence, nature, severity, and relatedness of adverse events (AEs), including all serious adverse events (SAEs)
Time Frame
Until 30 days after the end of study (64 months)
Title
Assess the effect on transfusion/ red blood cell (RBC) growth factor requirements (Phase 2 only) for WM only
Description
Change from Baseline (prior 1 month) transfusion/RBC growth factor requirement in frequency and volume in WM (Phase 2 only)
Time Frame
64 months
Title
Assess the effect on plasmapheresis requirements (Phase 2 only) for WM only
Description
Change from Baseline (prior 1 month) plasmapheresis requirement in frequency and volume in WM (Phase 2 only)
Time Frame
64 months
Title
Assess the effect on lymphoplasmacytic cells in the bone marrow (Phase 2 only) for WM only
Description
Change from Baseline in percent of lymphoplasmacytic cells in the bone marrow in WM (Phase 2 only)
Time Frame
64 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
History of previous clinically significant GI bleed in the last 6 months prior to first dose.
Female patients who are pregnant or lactating.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic Scottsdale
City
Scottsdale
State/Province
Arizona
Country
United States
Facility Name
Pacific Cancer Care
City
Salinas
State/Province
California
Country
United States
Facility Name
Colorado Blood Cancer Institute
City
Denver
State/Province
Colorado
Country
United States
Facility Name
Mayo Clinic
City
Jacksonville
State/Province
Florida
Country
United States
Facility Name
Winship Cancer Institute, Emory University
City
Atlanta
State/Province
Georgia
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
University of Maryland, Greenebaum Cancer Center
City
Baltimore
State/Province
Maryland
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Mass General Hospital
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Virginia Piper Cancer Institute
City
Minneapolis
State/Province
Minnesota
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
Country
United States
Facility Name
Washington University School of Medicine Division of Oncology
City
Saint Louis
State/Province
Missouri
Country
United States
Facility Name
John Theurer Cancer Center at Hackensack University
City
Hackensack
State/Province
New Jersey
Country
United States
Facility Name
Hematology Oncology of Northern New Jersey
City
Morristown
State/Province
New Jersey
Country
United States
Facility Name
New York Oncology Hematology
City
Albany
State/Province
New York
Country
United States
Facility Name
Mount Sinai Medical Center
City
New York
State/Province
New York
Country
United States
Facility Name
Sarah Cannon Research Institute / Tennessee Oncology, PLLC
City
Nashville
State/Province
Tennessee
Country
United States
Facility Name
Columbia Basin Hematology and Oncology
City
Kennewick
State/Province
Washington
Country
United States
12. IPD Sharing Statement
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Open-label Study of the Safety and Activity of Oprozomib in Patients With Hematologic Malignancies
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