Overview

This trial is active, not recruiting.

Condition multiple myeloma
Treatments oprozomib, pomalidomide, dexamethasone
Phase phase 1/phase 2
Target proteasome
Sponsor Onyx Therapeutics, Inc.
Start date November 2013
End date January 2017
Trial size 314 participants
Trial identifier NCT01999335, OPZ007

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Experimental)
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.
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.
pomalidomide
Study subjects will receive pomalidomide once-daily on Days 1-21 of every 28-day cycle.
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)
Phase 3: Study subjects will receive placebo in combination with pomalidomide and dexamethasone.
pomalidomide
Study subjects will receive pomalidomide once-daily on Days 1-21 of every 28-day cycle.
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 Outcomes

Measure
Progression-free Survival (PFS) - Phase 3
time frame: Approximately 14 months
Maximum Tolerated Dose (MTD) - Phase 1b
time frame: Approximately 6 months
Adverse Events (AEs) - Phase 1b & Phase 3
time frame: Until 30 days after the end of study (32 months)

Secondary Outcomes

Measure
Overall Survival (OS) - Phase 3
time frame: 14 months
Overall Response Rate (ORR) - Phase 1b & Phase 3
time frame: 31 months
Clinical Benefit Rate (CBR) - Phase 1b & Phase 3
time frame: 31 months
Duration of Response (DOR) - Phase 3
time frame: 31 months
Health-Related Quality of Life (HRQOL) - Phase 3
time frame: 31 months
Bone Pain - Phase 3
time frame: 31 months
Improvement in Renal Function - Phase 3
time frame: 31 months
Improvement in Hemoglobin - Phase 3
time frame: 31 months
Maximum Plasma Concentration (Cmax) - Phase 1b & Phase 3
time frame: 31 months
Time of Maximum Plasma Concentration (Tmax) - Phase 1b & Phase 3
time frame: 31 months
Total Plasma Exposure (AUC) - Phase 1b & Phase 3
time frame: 31 months

Eligibility Criteria

Male or female participants at least 18 years old.

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

Additional Information

Official title Phase 1b/3 Multicenter Study of Oprozomib, Pomalidomide, and Dexamethasone in Primary Refractory or Relapsed and Refractory Multiple Myeloma Subjects
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by Onyx Pharmaceuticals.
Location data was received from the National Cancer Institute and was last updated in August 2016.