AzTrials
AzTrials

Multiple MyelomaPhase 1/2NCT01416428

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

A Phase 1/2 study testing oprozomib in people with Multiple Myeloma and Waldenstrom Macroglobulinemia, run by Amgen at 19 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
oprozomib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
210 participants
Where
19 sitesUnited States
Study dates
15 Oct 2011to 12 Aug 2019
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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.

Who cannot join

  • 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.
Show all 15Show fewer
  • 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.

Trial locations and contacts

19 sites in 1 country.

19 sites in 1 country

United States19 sites

  • New York Oncology Hematology

    Albany, New York

  • Winship Cancer Institute, Emory University

    Atlanta, Georgia

  • University of Maryland, Greenebaum Cancer Center

    Baltimore, Maryland

  • Dana Farber Cancer Institute

    Boston, Massachusetts

  • Mass General Hospital

    Boston, Massachusetts

  • Rush University Medical Center

    Chicago, Illinois

  • University of Chicago Medical Center

    Chicago, Illinois

  • Colorado Blood Cancer Institute

    Denver, Colorado

  • John Theurer Cancer Center at Hackensack University

    Hackensack, New Jersey

  • Mayo Clinic

    Jacksonville, Florida

  • Columbia Basin Hematology and Oncology

    Kennewick, Washington

  • Virginia Piper Cancer Institute

    Minneapolis, Minnesota

  • Hematology Oncology of Northern New Jersey

    Morristown, New Jersey

  • Sarah Cannon Research Institute / Tennessee Oncology, PLLC

    Nashville, Tennessee

  • Mount Sinai Medical Center

    New York, New York

  • Mayo Clinic

    Rochester, Minnesota

  • Pacific Cancer Care

    Salinas, California

  • Mayo Clinic Scottsdale

    Scottsdale, Arizona

  • Washington University School of Medicine Division of Oncology

    St Louis, Missouri

Other trials in United States

About this study

Official title: 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.

Being tested
oprozomib
Keywords
multiple myeloma, waldenstrom macroglobulinemia
Medical subject headings
Multiple Myeloma, Waldenstrom Macroglobulinemia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • oprozomibDrug

    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.

Study groups in NCT01416428
Study groupRoleWhat they receive
QDx2 Dosing ScheduleExperimentalQDx2 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.
Receives: Drug: oprozomib
QDx5 Dosing ScheduleExperimentalQDx5 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.
Receives: Drug: oprozomib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: 6 weeks to 18 months

Secondary outcomes (17)

  1. 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.

    Measured: 64 months

  2. 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)

    Measured: 64 months

  3. 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)

    Measured: 64 months

  4. 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

    Measured: 64 months

  5. 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

    Measured: 64 months

  6. 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

    Measured: 55 months

  7. 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)

    Measured: 55 months

  8. 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

    Measured: 55 months

  9. 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.

    Measured: 55 months

  10. Change from Baseline in hematology laboratory results

    Assess the change from baseline in hematology panel

    Measured: 64 months

  11. Change from Baseline in serum chemistry results

    Assess the change from baseline in serum chemistry panel

    Measured: 64 months

  12. Change from Baseline in vital signs

    Assess the change from baseline in vital signs including blood pressure, pulse, and temperature

    Measured: 64 months

  13. Change from Baseline in weight

    Assess the change from baseline in weight

    Measured: 64 months

  14. 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)

    Measured: Until 30 days after the end of study (64 months)

  15. 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)

    Measured: 64 months

  16. 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)

    Measured: 64 months

  17. 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)

    Measured: 64 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2011 (estimated)
  2. Study start15 Oct 2011
  3. Primary completion8 Aug 2016
  4. Study completion12 Aug 2019

Why it 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.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
210 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01416428
Sponsor's protocol ID
2011-001
Status last verified
Nov 2022
First submitted
11 Aug 2011
Last updated
8 Nov 2022
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing oprozomib in people with Multiple Myeloma and Waldenstrom Macroglobulinemia, run by Amgen at 19 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Nov 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 19 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: 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.). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Determine the MTD (Phase 1) and ORR (Phase 2). (time frame: 6 weeks to 18 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01416428.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Nov 2022.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in