Open-label Study of the Safety and Activity of Oprozomib in Patients With Hematologic Malignancies
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ClinicalTrials.gov Identifier: NCT01416428 |
Recruitment Status :
Terminated
(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.)
First Posted : August 15, 2011
Last Update Posted : February 21, 2021
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Multiple Myeloma Waldenstrom Macroglobulinemia | Drug: oprozomib | Phase 1 Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 210 participants |
Allocation: | Non-Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Phase 1b/2, Multicenter, Open-label Study of the Safety and Activity of Oprozomib in Patients With Hematologic Malignancies |
Actual Study Start Date : | October 15, 2011 |
Actual Primary Completion Date : | August 8, 2016 |
Actual Study Completion Date : | August 12, 2019 |

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. |
- Determine the MTD (Phase 1) and ORR (Phase 2). [ Time Frame: 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).
- Evaluate the duration of response (DOR) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 64 months ]Assess the change from baseline in hematology panel
- Change from Baseline in serum chemistry results [ Time Frame: 64 months ]Assess the change from baseline in serum chemistry panel
- Change from Baseline in vital signs [ Time Frame: 64 months ]Assess the change from baseline in vital signs including blood pressure, pulse, and temperature
- Change from Baseline in weight [ Time Frame: 64 months ]Assess the change from baseline in weight
- Evaluate safety of oprozomib in Phase 2 [ Time Frame: 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)
- Assess the effect on transfusion/ red blood cell (RBC) growth factor requirements (Phase 2 only) for WM only [ Time Frame: 64 months ]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 [ Time Frame: 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 [ Time Frame: 64 months ]Change from Baseline in percent of lymphoplasmacytic cells in the bone marrow in WM (Phase 2 only)

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Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01416428

Study Director: | MD | Amgen |
Responsible Party: | Amgen |
ClinicalTrials.gov Identifier: | NCT01416428 |
Other Study ID Numbers: |
2011-001 |
First Posted: | August 15, 2011 Key Record Dates |
Last Update Posted: | February 21, 2021 |
Last Verified: | February 2021 |
multiple myeloma waldenstrom macroglobulinemia |
Multiple Myeloma Hematologic Neoplasms Waldenstrom Macroglobulinemia Neoplasms, Plasma Cell Neoplasms by Histologic Type Neoplasms Hemostatic Disorders Vascular Diseases Cardiovascular Diseases |
Paraproteinemias Blood Protein Disorders Hematologic Diseases Hemorrhagic Disorders Lymphoproliferative Disorders Immunoproliferative Disorders Immune System Diseases Neoplasms by Site Lymphatic Diseases |