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

Multiple Myeloma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01416428
• Other study ID #: 2011-001
• Status: Terminated
• Phase: Phase 1/Phase 2
• 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
• 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.

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Multiple Myeloma
• Waldenstrom Macroglobulinemia

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

External Links

•   AmgenTrials clinical trials website