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A Study of Oprozomib, Pomalidomide, and Dexamethasone in Subjects With Primary Refractory or Relapsed and Refractory Multiple Myeloma

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ClinicalTrials.gov Identifier: NCT01999335
Recruitment Status : Completed
First Posted : December 3, 2013
Last Update Posted : October 17, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief Summary:

The purpose of Phase 1 of the study is to determine the maximum tolerated dose and assess the safety, tolerability and activity of oprozomib in combination with pomalidomide and dexamethasone in subjects with primary refractory or relapsed and refractory multiple myeloma.

The purpose of Phase 3 of the study is to compare the key outcome measures for subjects with primary refractory or relapsed and refractory multiple myeloma who are randomized to either oprozomib or placebo in combination with pomalidomide and dexamethasone.


Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Oprozomib Drug: Pomalidomide Drug: Dexamethasone Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 33 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Phase 1b/3 Multicenter Study of Oprozomib, Pomalidomide, and Dexamethasone in Primary Refractory or Relapsed and Refractory Multiple Myeloma Subjects
Study Start Date : November 2013
Actual Primary Completion Date : April 25, 2019
Actual Study Completion Date : April 25, 2019


Arm Intervention/treatment
Experimental: Oprozomib with Pomalidomide and Dexamethasone (OPomd)

Phase 1b:

Oprozomib doses will be escalated in sequential groups of at least 3 subjects. Study subjects will receive oprozomib in combination with pomalidomide and dexamethasone. Assuming no dose de-escalation is needed, pomalidomide and dexamethasone doses will remain fixed, while the dose of oprozomib for subsequent cohorts will be escalated until the MTD is reached.

Phase 3:

Study subjects will receive oprozomib in combination with pomalidomide and dexamethasone.

Drug: Oprozomib
Study subjects will receive oprozomib tablets once daily on Days 1-5 and 15-19 (QD × 5 bimonthly schedule) of each 28-day treatment cycle.

Drug: Pomalidomide
Study subjects will receive pomalidomide once-daily on Days 1-21 of every 28-day cycle.

Drug: Dexamethasone
Study subjects will receive dexamethasone once daily on days 1-2, 8-9, 15-16, and 22-23 of every 28-day cycle.

Placebo Comparator: Placebo with Pomalidomide and Dexamethasone (Pomd)

Phase 3:

Study subjects will receive placebo in combination with pomalidomide and dexamethasone.

Drug: Pomalidomide
Study subjects will receive pomalidomide once-daily on Days 1-21 of every 28-day cycle.

Drug: Dexamethasone
Study subjects will receive dexamethasone once daily on days 1-2, 8-9, 15-16, and 22-23 of every 28-day cycle.




Primary Outcome Measures :
  1. Progression-free Survival (PFS) - Phase 3 [ Time Frame: Approximately 14 months ]
    To compare progression-free survival (PFS), as determined by Onyx Response Computational Assessment (ORCA) according to the IMWG-URC, between subjects treated with oprozomib in combination with pomalidomide and dexamethasone (OPomd) and those treated with pomalidomide and dexamethasone (Pomd)

  2. Maximum Tolerated Dose (MTD) - Phase 1b [ Time Frame: Approximately 6 months ]
    To determine the maximum tolerated dose (MTD) and identify the recommended Phase 3 dose (RP3) of oprozomib in combination with pomalidomide and dexamethasone (OPomd) in subjects with primary refractory or relapsed and refractory multiple myeloma

  3. Adverse Events (AEs) - Phase 1b & Phase 3 [ Time Frame: Until 30 days after the end of study (32 months) ]
    Number of patients that experience Adverse Events (AEs)


Secondary Outcome Measures :
  1. Overall Survival (OS) - Phase 3 [ Time Frame: 14 months ]
    Overall Survival (OS) is defined as time from randomization to death due to any cause.

  2. Overall Response Rate (ORR) - Phase 1b & Phase 3 [ Time Frame: 31 months ]
    To estimate the overall response rate (ORR) of oprozomib in combination with pomalidomide and dexamethasone (OPomd), defined as the proportion of subjects with a best overall response of stringent complete response (sCR), complete response (CR), very good partial response (VGPR), or partial response (PR) as determined by investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC)

  3. Clinical Benefit Rate (CBR) - Phase 1b & Phase 3 [ Time Frame: 31 months ]
    To estimate the clinical benefit rate (CBR) of oprozomib in combination with pomalidomide and dexamethasone (OPomd), defined as the proportion of subjects with best overall response of minimal response (MR) or better as determined by investigator according to the International Myeloma Working Group Uniform Response Criteria (IMWG-URC) and modified European Group for Blood and Marrow Transplantation (EBMT) criteria

  4. Duration of Response (DOR) - Phase 3 [ Time Frame: 31 months ]
    Duration of Response (DOR) is defined as the time from the first evidence of confirmed partial response (PR) or better to disease progression or death due to any cause as determined by ORCA according to the IMWG-URC and modified EBMT criteria.

  5. Health-Related Quality of Life (HRQOL) - Phase 3 [ Time Frame: 31 months ]
    Changes in health-related quality of life (HRQOL) using the EORTC QLQ-C30 Global Health Status/QOL scale

  6. Bone Pain - Phase 3 [ Time Frame: 31 months ]
    Measures of bone pain using the brief pain index (BPI), EORTC QLQ-MY20, and selected subscales of the EORTC QLQ-C30

  7. Improvement in Renal Function - Phase 3 [ Time Frame: 31 months ]
    Improvement in renal function over time, as defined by an increase in glomerular filtration rate (GFR) of at least 10 mL/min

  8. Improvement in Hemoglobin - Phase 3 [ Time Frame: 31 months ]
    Improvement in hemoglobin over time, as defined by an increase of ≥ 2 g/dL

  9. Maximum Plasma Concentration (Cmax) - Phase 1b & Phase 3 [ Time Frame: 31 months ]
    Maximum plasma concentration (Cmax)

  10. Time of Maximum Plasma Concentration (Tmax) - Phase 1b & Phase 3 [ Time Frame: 31 months ]
    Time of Maximum Plasma Concentration (Tmax)

  11. Total Plasma Exposure (AUC) - Phase 1b & Phase 3 [ Time Frame: 31 months ]
    Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration and to infinity (AUC0-last and AUC0-∞)



Information from the National Library of Medicine

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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

Key Inclusion Criteria:

  1. Multiple myeloma that is primary refractory or relapsed and refractory after at least 2 lines of standard for multiple myeloma including:

    a. > 2 consecutive cycles of both bortezomib and lenalidomide or thalidomide (alone or in combination) i. Patients who received bortezomib as their last therapy who were not refractory but developed bortezomib intolerance, as defined by the development of Grade 2 peripheral neuropathy with pain or > Grade 3 peripheral neuropathy after ≥ 2 consecutive cycles, are eligible

    b. Adequate alkylator therapy defined as: i. High-dose melphalan or other alkylating agent as conditioning for autologous or allogeneic stem cell transplant (SCT), or ii. ≥ 6 cycles of induction therapy, or iii. PD after ≥ 2 cycles

  2. Disease progression on or within 60 days of completion of the last therapy
  3. Measurable disease as indicated by 1 or more of the following:

    1. Serum M-protein ≥ 500 mg/dL
    2. Urine M-protein ≥ 200 mg/24 h
    3. For patients without measurable serum or urine M protein, serum free light chain (SFLC): Involved free light chain (FLC) concentration ≥ 10 mg/dL provided SFLC ratio is abnormal
  4. Males and females ≥ 18 years old
  5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

Key Exclusion Criteria:

  1. Systemic chemotherapy with approved or investigational anticancer therapeutics, including steroid therapy intended to treat underlying malignancy, within 3 weeks before the first dose or 6 weeks for antibody therapy
  2. Dexamethasone at cumulative doses greater than 160 mg or equivalent within 14 days prior to the first dose of study treatment is not allowed. Use of topical or inhaled steroids is acceptable.
  3. Radiation therapy within 3 weeks before first dose. Radioimmunotherapy within 8 weeks before first dose.
  4. Autologous SCT within 8 weeks and allogeneic SCT within 16 weeks prior to initiation of study treatment. Patients with prior allogeneic SCT should not have evidence of moderate-to-severe graft-versus-host disease (as defined in Filipovich 2005).
  5. Known hypersensitivity to any immunomodulatory drugs (IMiDs), including Grade 4 rash
  6. Prior treatment of any duration with pomalidomide
  7. Known hypersensitivity or intolerance to dexamethasone
  8. Prior exposure to oprozomib
  9. Congestive heart failure (New York Heart Association Class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention, or myocardial infarction within 6 months before first dose

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): NCT01999335


Locations
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Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT01999335    
Other Study ID Numbers: OPZ007
First Posted: December 3, 2013    Key Record Dates
Last Update Posted: October 17, 2019
Last Verified: October 2019
Additional relevant MeSH terms:
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Multiple Myeloma
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
Dexamethasone
Pomalidomide
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Immunologic Factors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents