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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT01416428
Other study ID # 2011-001
Secondary ID
Status Terminated
Phase Phase 1/Phase 2
First received
Last updated
Start date October 15, 2011
Est. completion date August 12, 2019

Study information

Verified date November 2022
Source Amgen
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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


Recruitment information / eligibility

Status Terminated
Enrollment 210
Est. completion date August 12, 2019
Est. primary completion date August 8, 2016
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility 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 Design


Intervention

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.

Locations

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

Sponsors (1)

Lead Sponsor Collaborator
Amgen

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary Change from Baseline in hematology laboratory results Assess the change from baseline in hematology panel 64 months
Secondary Change from Baseline in serum chemistry results Assess the change from baseline in serum chemistry panel 64 months
Secondary Change from Baseline in vital signs Assess the change from baseline in vital signs including blood pressure, pulse, and temperature 64 months
Secondary Change from Baseline in weight Assess the change from baseline in weight 64 months
Secondary 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)
Secondary 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
Secondary 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
Secondary 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
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