Phase 1b Study Evaluating OPomD in Relapsed or Refractory Multiple Myeloma

NCT02939183 | Completed Phase 1 Results

• 1 other identifier: 20160104
• Study Type: interventional
• Target: 61
• Locations: 4 countries
• Sites: 20

Brief Summary

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

Conditions

Relapsed or Refractory Multiple Myeloma

Keywords

Multiple Myeloma

Outcome Measures

Primary Outcomes (4)

• Number of Participants Who Experienced Dose-Limiting Toxcity (DLT)

  DLTs were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 and included the below, if judged by the investigator/medical monitor to be possibly related to study treatment: Non-hematologic DLTs were any ≥ Grade 3 toxicity, except: Grade 3 asymptomatic electrolyte abnormalities (except hypophosphatemia \> 24 hours); Grade 3 nausea, vomiting and diarrhea \< 3 days; Grade 3 fatigue \< 14 days; ≥ Grade 3 hyperglycemia/toxicity due to dexamethasone; ≥ Grade 3 rash due to pomalidomide. Hematologic DLTs included: Grade 4 neutropenia if absolute neutrophil count \< 0.5 x 10\^9/L ≥ 7 days; febrile neutropenia; Grade 4 thrombocytopenia ≥ 7 days; Grade ≥ 3 with ≥ Grade 2 bleeding/requiring platelet transfusion.

  Day 1 to day 28 of cycle 1, where each cycle was 28 days

• Maximum Tolerated Dose (MTD) of Each Formulation of Oprozomib in Combination With Pomolidomide and Dexamethasone

  The MTD was the dose with the highest posterior probability of having a DLT rate within the target toxicity interval (15% to 25%), while the posterior probability of excessive/unacceptable toxicity (\>25% to 100%) is \<40%. DLTs were graded using CTCAE version 4.03 and included the below, if judged by the investigator/medical monitor to be possibly related to study treatment: Non-hematologic DLTs were any ≥ Grade 3 toxicity, except: Grade 3 asymptomatic electrolyte abnormalities (except hypophosphatemia \> 24 hours); Grade 3 nausea, vomiting and diarrhea \< 3 days; Grade 3 fatigue \< 14 days; ≥ Grade 3 hyperglycemia/toxicity due to dexamethasone; ≥ Grade 3 rash due to pomalidomide. Hematologic DLTs included: Grade 4 neutropenia if absolute neutrophil count \< 0.5 x 10\^9/L ≥ 7 days; febrile neutropenia; Grade 4 thrombocytopenia ≥ 7 days; Grade ≥ 3 with ≥ Grade 2 bleeding/requiring platelet transfusion.

  Day 1 to Day 28 of cycle 1, where each cycle was 28 days

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) (Oprozomib in Combination With Dexamethasone and/or Pomalidomide)

  An adverse event (AE) is defined as any untoward medical occurrence in a clinical trial participant. TEAEs were any AE that started on or after receiving the first dose of investigational product and up to and including 30 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered related to study treatment by the investigator. Any clinically significant changes in electrocardiograms, vital signs, physical examination with a neurological assessment and clinical laboratory tests were recorded as TEAEs.

  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

• Number of Participants With TEAEs and Treatment-emergent Serious AEs (Open-label Roll-over)

  TEAEs were any AE that started on or after receiving the first dose of investigational product and up to and including 30 days after the last dose of investigational product or the end of study date, whichever is earlier. Treatment-related TEAEs were those considered related to study treatment by the investigator. Serious TEAEs were any AE meeting at least 1 of the following criteria: fatal; life-threatening; required in-patient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; congenital anomaly/birth defect; other medically important serious event.

  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 (8)

• Maximum Observed Concentration (Cmax) of Oprozomib

  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

• Time to Cmax (Tmax) of Oprozomib

  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

• Area Under the Concentration-time Curve From Time 0 to the Time of the Last Quantifiable Concentration (AUClast) of Oprozomib

  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

• Best Overall Response (BOR) According to Revised International Myeloma Working Group Uniform Response Criteria (IMWG-URC)

  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

• Overall Response Rate (ORR) According to IMWG-URC

  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

Study Arms (5)

Part 1 Oprozomib Immediate-release (IR) + Dexamethasone

EXPERIMENTAL

Oprozomib IR plus dexamethasone

Drug: Immediate Release (IR) Formulation; Drug: Dexamethasone

Part 1 Oprozomib Gastro-retentive (GR) + Dexamethasone

EXPERIMENTAL

Oprozomib GR plus dexamethasone

Drug: Gastro-Retentive (GR) Formulation; Drug: Dexamethasone

Part 2 Oprozomib IR + Pomalidomide + Dexamethasone

EXPERIMENTAL

Oprozomib IR plus pomalidomide and dexamethasone

Drug: Immediate Release (IR) Formulation; Drug: Dexamethasone; Drug: Pomalidomide

Part 2 Oprozomib GR + Pomalidomide + Dexamethasone

EXPERIMENTAL

Oprozomib GR plus pomalidomide and dexamethasone

Drug: Gastro-Retentive (GR) Formulation; Drug: Dexamethasone; Drug: Pomalidomide

Open-label Roll-over

EXPERIMENTAL

Oprozomib GR monotherapy, or oprozomib GR plus dexamethasone

Drug: Gastro-Retentive (GR) Formulation; Drug: Dexamethasone

Interventions

Immediate Release (IR) Formulation DRUG

Immediate Release (IR) Formulation

Part 1 Oprozomib Immediate-release (IR) + Dexamethasone; Part 2 Oprozomib IR + Pomalidomide + Dexamethasone

Gastro-Retentive (GR) Formulation DRUG

Gastro-Retentive (GR) Formulation

Open-label Roll-over; Part 1 Oprozomib Gastro-retentive (GR) + Dexamethasone; Part 2 Oprozomib GR + Pomalidomide + Dexamethasone

Dexamethasone DRUG

Dexamethasone

Open-label Roll-over; Part 1 Oprozomib Gastro-retentive (GR) + Dexamethasone; Part 1 Oprozomib Immediate-release (IR) + Dexamethasone; Part 2 Oprozomib GR + Pomalidomide + Dexamethasone; Part 2 Oprozomib IR + Pomalidomide + Dexamethasone

Pomalidomide DRUG

Pomalidomide

Part 2 Oprozomib GR + Pomalidomide + Dexamethasone; Part 2 Oprozomib IR + Pomalidomide + Dexamethasone

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (20)

Research Site

West Hollywood, California, 90069, United States

Location

Research Site

Tampa, Florida, 33612, United States

Location

Research Site

Atlanta, Georgia, 30322, United States

Location

Research Site

Chicago, Illinois, 60637-6613, United States

Location

Research Site

Bethesda, Maryland, 20817, United States

Location

Research Site

St Louis, Missouri, 63110, United States

Location

Research Site

Hackensack, New Jersey, 07601, United States

Location

Research Site

New York, New York, 10021, United States

Location

Research Site

Charlotte, North Carolina, 28204, United States

Location

Research Site

Canton, Ohio, 44718, United States

Location

Research Site

Cleveland, Ohio, 44195, United States

Location

Research Site

San Antonio, Texas, 78229, United States

Location

Research Site

Milwaukee, Wisconsin, 53226, United States

Location

Research Site

Clayton, Victoria, 3168, Australia

Location

Research Site

Murdoch, Western Australia, 6150, Australia

Location

Research Site

Perth, Western Australia, 6000, Australia

Location

Research Site

Calgary, Alberta, T2N 2T9, Canada

Location

Research Site

Toronto, Ontario, M5G 2C1, Canada

Location

Research Site

Salamanca, Castille and León, 37007, Spain

Location

Research Site

Pamplona, Navarre, 31008, Spain

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Recurrence; Multiple Myeloma

Interventions

Dosage Forms; Dexamethasone; pomalidomide

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2016
• First Posted: October 19, 2016
• Study Start: January 17, 2017
• Primary Completion: October 6, 2022
• Study Completion: October 6, 2022
• Last Updated: September 26, 2024
• Results First Posted: September 26, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

CA (2); AU (3); US (13); ES (2)