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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
Sponsor:
Information provided by (Responsible Party):
Amgen

Study Description
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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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Waldenstrom Macroglobulinemia Drug: oprozomib Phase 1 Phase 2

Study Design
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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

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma

Arms and Interventions
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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.


Outcome Measures
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Primary Outcome Measures :
  1. 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).



Secondary Outcome Measures :
  1. 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.

  2. 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)

  3. 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)

  4. 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

  5. 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

  6. 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

  7. 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)

  8. 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

  9. 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.

  10. Change from Baseline in hematology laboratory results [ Time Frame: 64 months ]
    Assess the change from baseline in hematology panel

  11. Change from Baseline in serum chemistry results [ Time Frame: 64 months ]
    Assess the change from baseline in serum chemistry panel

  12. Change from Baseline in vital signs [ Time Frame: 64 months ]
    Assess the change from baseline in vital signs including blood pressure, pulse, and temperature

  13. Change from Baseline in weight [ Time Frame: 64 months ]
    Assess the change from baseline in weight

  14. 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)

  15. 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)

  16. 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)

  17. 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)


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Contacts and Locations
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Information from the National Library of Medicine

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


Locations
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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
More Information
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Additional Information:

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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
Keywords provided by Amgen:
multiple myeloma
waldenstrom macroglobulinemia
Additional relevant MeSH terms:
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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