Clinical trial NCT02939183: Phase 1b Study Evaluating OPomD in Relapsed or Refractory Multiple Myeloma
Official title: (INTREPID-1) A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of Oprozomib in Combination With Pomalidomide and Dexamethasone in Subjects With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed or Refractory Multiple Myeloma
Keywords: Multiple Myeloma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2016-10-19
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A study evaluating two new formulations of oprozomib plus pomalidomide and dexamethasone in participants with relapsed refractory multiple myeloma.

Detailed description: A multicenter, non-randomized, open-label, dose-exploration study evaluating two new formulations of oprozomib plus pomalidomide and dexamethasone in participants with relapsed refractory multiple myeloma. The study will be conducted in two parts. Part 1 will evaluate the formulations of oprozomib in combination with dexamethasone only. Part 2 will evaluate the formulations of oprozomib administered at increasing dose levels (dose escalation) in combination with pomalidomide and dexamethasone.

Eligibility criteria: Inclusion criteria

* Participant must have a pathologically documented, definitively diagnosed, multiple myeloma relapse, or refractory progressive disease after at least 2 lines of therapy for multiple myeloma. Prior therapeutic treatment or regimens must include a proteasome inhibitor and lenalidomide.
* Participant must be willing and able to undergo bone marrow aspirate per protocol (with or without bone marrow biopsy per institutional guidelines).
* Measurable disease (assessed within 28 days prior to day 1).
* Eastern Cooperative Oncology Group (ECOG) performance status of \<= 2.
* Other Inclusion Criteria May Apply

Exclusion Criteria

* Currently receiving treatment in another investigational device or drug study, or less than 28 days or 5 half-lives whichever is shorter since ending treatment on another investigational device or drug study(s).
* Previously received an allogeneic stem cell transplant and the occurrence of one or more of the following: received the transplant within 6 months prior to study day 1; received immunosuppressive therapy within the last 3 months prior to study day 1; having signs or symptoms of acute or chronic graft-versus-host disease.
* Autologous stem cell transplant \< 90 days prior to study day 1.
* Multiple myeloma with IgM subtype.
* POEM syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
* Plasma cell leukemia (\> 2.0 X10\^9/L circulating plasma cells by standard differential).
* Waldenstrom's macroglobulinemia.
* Other Exclusion Criteria May Apply

Primary outcomes:
measure: Number of Participants Who Experienced Dose-Limiting Toxcity (DLT)
timeFrame: Day 1 to day 28 of cycle 1, where each cycle was 28 days
measure: Maximum Tolerated Dose (MTD) of Each Formulation of Oprozomib in Combination With Pomolidomide and Dexamethasone
timeFrame: Day 1 to Day 28 of cycle 1, where each cycle was 28 days
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Oprozomib in Combination With Dexamethasone and/or Pomalidomide)
timeFrame: Day 1 of cycle 1 to 30 (+7) days after the last dose of study treatment or end of study date, whichever is earlier (where each cycle was 28 days). Median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
measure: Number of Participants With TEAEs and Treatment-emergent Serious AEs (Open-label Roll-over)
timeFrame: Day 1 to 30 (+7) days after the last dose of study treatment or end of study date, whichever is earlier (where each cycle was 28 days). Median treatment duration for the open-label roll-over arm was 75.14 weeks
Secondary outcomes:
measure: Maximum Observed Concentration (Cmax) of Oprozomib
timeFrame: Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
measure: Time to Cmax (Tmax) of Oprozomib
timeFrame: Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
measure: Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Oprozomib
timeFrame: Cycle 1 days 8 and 22: pre-dose, 0.5, 1, 2, 4, and 6 hours post-dose. GR only: cycle 1 day 8: 8 hours post-dose
measure: Best Overall Response (BOR) According to Revised International Myeloma Working Group Uniform Response Criteria (IMWG-URC)
timeFrame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
measure: Overall Response Rate (ORR) According to IMWG-URC
timeFrame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
measure: Number of Participants With Progression Free Survival (PFS) Events
timeFrame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
measure: Kaplan-Meier Estimate of PFS
timeFrame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
measure: Kaplan-Meier Estimate of Duration of Response (DOR)
timeFrame: Day 1 of cycle 1 up to the end of study visit (where each cycle was 28 days); median treatment duration in Part 1 was 11.43 weeks and in Part 2 was 28 weeks
Other outcomes:
Locations:
city: West Hollywood
country: United States
facility: Research Site
state: California
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Atlanta
country: United States
facility: Research Site
state: Georgia
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Bethesda
country: United States
facility: Research Site
state: Maryland
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Hackensack
country: United States
facility: Research Site
state: New Jersey
city: New York
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Canton
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Clayton
country: Australia
facility: Research Site
state: Victoria
city: Murdoch
country: Australia
facility: Research Site
state: Western Australia
city: Perth
country: Australia
facility: Research Site
state: Western Australia
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Salamanca
country: Spain
facility: Research Site
state: Castilla León
city: Pamplona
country: Spain
facility: Research Site
state: Navarra
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: