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

Sponsor
Amgen (Industry)
Overall Status
Terminated
CT.gov ID
NCT01416428
Collaborator
(none)
210
19
2
93.9
11.1
0.1

Study Details

Study Description

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
Phase 1/Phase 2

Study Design

Study Type:
Interventional
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 :
Oct 15, 2011
Actual Primary Completion Date :
Aug 8, 2016
Actual Study Completion Date :
Aug 12, 2019

Arms and Interventions

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

Primary Outcome Measures

  1. Determine the MTD (Phase 1) and ORR (Phase 2). [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) [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) [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) [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 [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 [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) [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) [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) [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) [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 [64 months]

    Assess the change from baseline in hematology panel

  11. Change from Baseline in serum chemistry results [64 months]

    Assess the change from baseline in serum chemistry panel

  12. Change from Baseline in vital signs [64 months]

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

  13. Change from Baseline in weight [64 months]

    Assess the change from baseline in weight

  14. Evaluate safety of oprozomib in Phase 2 [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 [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 [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 [64 months]

    Change from Baseline in percent of lymphoplasmacytic cells in the bone marrow in WM (Phase 2 only)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
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.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Mayo Clinic Scottsdale Scottsdale Arizona United States
2 Pacific Cancer Care Salinas California United States
3 Colorado Blood Cancer Institute Denver Colorado United States
4 Mayo Clinic Jacksonville Florida United States
5 Winship Cancer Institute, Emory University Atlanta Georgia United States
6 Rush University Medical Center Chicago Illinois United States
7 University of Chicago Medical Center Chicago Illinois United States
8 University of Maryland, Greenebaum Cancer Center Baltimore Maryland United States
9 Dana Farber Cancer Institute Boston Massachusetts United States
10 Mass General Hospital Boston Massachusetts United States
11 Virginia Piper Cancer Institute Minneapolis Minnesota United States
12 Mayo Clinic Rochester Minnesota United States
13 Washington University School of Medicine Division of Oncology Saint Louis Missouri United States
14 John Theurer Cancer Center at Hackensack University Hackensack New Jersey United States
15 Hematology Oncology of Northern New Jersey Morristown New Jersey United States
16 New York Oncology Hematology Albany New York United States
17 Mount Sinai Medical Center New York New York United States
18 Sarah Cannon Research Institute / Tennessee Oncology, PLLC Nashville Tennessee United States
19 Columbia Basin Hematology and Oncology Kennewick Washington United States

Sponsors and Collaborators

  • Amgen

Investigators

  • Study Director: MD, Amgen

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT01416428
Other Study ID Numbers:
  • 2011-001
First Posted:
Aug 15, 2011
Last Update Posted:
Nov 16, 2021
Last Verified:
Nov 1, 2021

Study Results

No Results Posted as of Nov 16, 2021