Study of Oprozomib and Dexamethasone, in Combination With Lenalidomide or Oral Cyclophosphamide in Patients With Newly Diagnosed Multiple Myeloma

• ClinicalTrials.gov Identifier: NCT01881789
• Recruitment Status: Completed
• First Posted: June 20, 2013
• Last Update Posted: October 17, 2019
• Sponsor: Amgen
• Information provided by (Responsible Party): Amgen

Tracking Information

• First Submitted Date: June 13, 2013
• First Posted Date: June 20, 2013
• Last Update Posted Date: October 17, 2019
• Study Start Date: August 2013
• Actual Primary Completion Date: September 23, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 16, 2015)

• Maximum Tolerated Dose (MTD) [ Time Frame: 6 months ]
  For each dosing schedule, the MTD will be defined as the highest dose at which a DLT is observed in fewer than 2 of 6 patients. DLT is defined as any of the following treatment-related events occurring in the first 28 days of treatment.
• Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 36 months ]
  Safety and tolerability of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide, as defined by the type, incidence, severity, and outcome of Adverse Events (AEs).
• Overall Response Rate (ORR) [ Time Frame: 14 months ]
  The antitumor activity of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide, as measured by overall response rate (ORR).
• Complete Response Rate (CRR) [ Time Frame: 17 months ]
  The antitumor activity of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide, as measured by complete response rate (CRR).

Original Primary Outcome Measures (submitted: June 17, 2013)

• To establish the maximum tolerated dose (MTD) of oprozomib administered orally in combination with lenalidomide and dexamethasone [ Time Frame: 6 months ]
• To estimate the overall response rate (ORR) [ Time Frame: 14 months ]
• To estimate the complete response rate (CRR) [ Time Frame: 17 months ]

• Change History: Complete list of historical versions of study NCT01881789 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: March 16, 2015)

• Population Pharmacokinetic (PK) Parameters - Apparent Clearance [ Time Frame: 18 months ]
  The Apparent Clearance is defined as the amount of drug administered (dose) divided by the plasma concentration-time curve (AUC) of oprozomib and its metabolites at various time points.
• Population Pharmacokinetic (PK) Parameters - Volume of Distribution [ Time Frame: 18 months ]
  The Volume of Distribution is defined as the amount of oprozomib administered (dose) divided by initial oprozomib plasma concentration.
• Duration of Response (DOR) [ Time Frame: 42 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.
• Progression-Free Survival (PFS) [ Time Frame: 42 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.

Original Secondary Outcome Measures (submitted: June 17, 2013)

• To evaluate the safety and tolerability of oprozomib administered in combination with lenalidomide and dexamethasone [ Time Frame: 36 months ]
  Evaluated by number of participants with adverse events
• To evaluate population pharmacokinetic (PK) parameter estimates of oprozomib and variability in these estimates when administered in combination with lenalidomide and dexamethasone [ Time Frame: 18 months ]
  Based on plasma concentration of oprozomib and its metabolites at various time points
• To estimate the duration of response (DOR) [ Time Frame: 42 months ]
• To estimate progression-free survival (PFS) [ Time Frame: 42 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Oprozomib and Dexamethasone, in Combination With Lenalidomide or Oral Cyclophosphamide in Patients With Newly Diagnosed Multiple Myeloma
• Official Title: Phase 1b/2, Multicenter, Open-label Study of Oprozomib and Dexamethasone, in Combination With Lenalidomide or Oral Cyclophosphamide in Patients With Newly Diagnosed Multiple Myeloma

Brief Summary

Phase 1b:

• To establish the maximum tolerated dose (MTD) of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide
• To evaluate the safety and tolerability of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide

Phase 2:

• To estimate the overall response rate (ORR) and complete response rate (CRR)
• To evaluate the safety and tolerability of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide

Secondary Objectives:

• To evaluate population pharmacokinetic (PK) parameter estimates of oprozomib and variability in these estimates when administered in combination with dexamethasone and lenalidomide or oral cyclophosphamide
• To estimate the duration of response (DOR)
• To estimate progression-free survival (PFS)

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• Drug: Oprozomib
  Subjects will receive Oprozomib extended release (ER) Tablets (hereafter referred to as oprozomib) administered orally, once daily on 1, 2, 8, 9, 15,16, 22 and 23 of 28-day cycles
  Other Name: Oprozomib ER tablets
• Drug: Lenalidomide
  Subjects will receive lenalidomide 25 mg on Days 1-21 of 28 day cycles
  Other Name: Revlimid
• Drug: Dexamethasone
  Subjects will receive dexamethasone 20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23 of 28 day cycles
• Drug: Cyclophosphamide
  Subjects will receive cyclophophamide 300 mg/m2 on Days 1, 8 and 15 of 28 day cycles
  Other Name: Cytoxan

Study Arms

• Experimental: Oprozomib, Lenalidomide and Dexamethasone (ORd)
  Subjects will receive oprozomib administered orally, once daily on Days 1, 2, 8, 9, 15,16, 22 and 23 in combination with lenalidomide at a dose of 25 mg on Days 1-21, and dexamethasone at a dose of 20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23 of 28-day cycles.
  Interventions:

  • Drug: Oprozomib
  • Drug: Lenalidomide
  • Drug: Dexamethasone
• Experimental: Oprozomib, Cyclophosphamide and Dexamethasone (OCyd)
  Subjects will receive oprozomib administered orally, once daily on Days 1, 2, 8, 9, 15, 16, 22 and 23 in combination with oral cyclophosphamide at a dose of 300 mg/m2 on Days 1, 8, and 15, and dexamethasone at a dose of 20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23 of 28-day cycles
  Interventions:

  • Drug: Oprozomib
  • Drug: Dexamethasone
  • Drug: Cyclophosphamide

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 8, 2019): 22
• Original Estimated Enrollment (submitted: June 17, 2013): 59
• Actual Study Completion Date: September 23, 2019
• Actual Primary Completion Date: September 23, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Newly diagnosed, symptomatic multiple myeloma patients for whom treatment is indicated per the NCCN guidelines, and for whom a hematopoietic stem cell transplant is not planned or scheduled during the study or are considered ineligible for hematopoietic stem cell transplant, with measurable disease
• Creatinine clearance of ≥ 50 mL/min (measured or calculated using the Cockcroft and Gault formula)

Key Exclusion Criteria:

• Any prior systemic antimyeloma therapy except oral steroids (dexamethasone up to a total dose of 160 mg or equivalent within 14 days prior to the first dose of study treatment). Use of topical or inhaled steroids is acceptable
• Radiation therapy within 2 weeks prior to first dose
• Major surgery within 3 weeks prior to first dose
• Active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to first dose
• Clinical significant gastrointestinal bleeding in the 6 months prior to Cycle 1 Day 1 (C1D1) first dose
• Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of first dose
• Other malignancy within the past 3 years except those considered cured by surgical resection including some cases of: with the exception of adequately treated basal or squamous cell carcinoma of the skin, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the breast or cervix, carcinoma in situ of the breast, prostate cancer with Gleason Score 6 or less with stable prostate specific antigen levels., or cancer considered cured by surgical resection

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01881789
• Other Study ID Numbers: OPZ003
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Amgen
• Study Sponsor: Amgen
• Collaborators: Not Provided

Investigators

• Study Director: MD; Amgen

• PRS Account: Amgen
• Verification Date: October 2019