Clinical trial NCT01881789: Oprozomib and Dexamethasone,in Combination With Lenalidomide or Oral Cyclophosphamide to Treat 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Keywords: multiple myeloma
proteasome inhibitor
oprozomib
orpozomib tablets
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2013-06-20
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objectives of this study included the following:

Phase 1b:

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

Phase 2:

* To estimate the antitumor activity of each combination regimen, as measured by overall response rate (ORR) and complete response rate (CRR)
* To evaluate the safety and tolerability of each combination regimens, as assessed by the type, incidence, severity and seriousness of adverse events, and abnormalities in selected laboratory analytes

Detailed description: Phase 1b used a standard 3 + 3 dose-escalation scheme to determine the MTD. For each combination regimen, oprozomib doses were to be escalated in sequential cohorts of 3 participants with expansion to up to 6 participants if a dose-limiting toxicity (DLT) was observed in 1 of the first 3 participants. The doses of lenalidomide, cyclophosphamide, and dexamethasone were to remain fixed in all dose cohorts.

The phase 2 portion of the study was to include up to 35 additional participants in each of the 2 combination regimens, treated at the recommended phase 2 dose (RP2D) of oprozomib that was identified during the phase 1b portion of the study in order to better characterize safety and tolerability, and antimyeloma activity.

This study was stopped by sponsor decision during the dose escalation in phase 1b prior to initiation of phase 2.

Eligibility criteria: Key Inclusion Criteria:

* Newly diagnosed, symptomatic multiple myeloma patients for whom treatment is indicated per the National Comprehensive Cancer Network (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

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Cycle 1, 28 days
measure: Number of Participants With Treatment-emergent Adverse Events (AEs)
timeFrame: From first dose of any study treatment to 30 days after last dose; median duration of treatment was 29.1, 12.4, 11.3, 66.6, 7.8, and 46.4 weeks in each treatment group, respectively.
Secondary outcomes:
measure: Plasma Oprozomib Concentration
timeFrame: Cycle 1 day 1 at 1 to 2.5 hours and 2.75 to 5 hours after end of infusion (EOI) and cycle 3 day 1 at predose and 1 to 2.5 hours and 2.75 to 5 hours after EOI.
measure: Overall Response Rate (ORR)
timeFrame: Disease response was assessed every 4 weeks for 24 cycles then every 8 weeks until end of treatment; median duration of treatment at the analysis cutoff date of 18 July 2016 was 29.1, 12.4, 11.3, 66.6, 7.8 and 46.4 weeks in each group, respectively
measure: Duration of Response (DOR)
timeFrame: Disease response was assessed every 4 weeks for 24 cycles then every 8 weeks until end of treatment; median time on follow-up at the analysis cut-off date of 18 July 2016 was 14.1, 3.5, 2.6, 16.0, 3.6, and 11.2 months in each group, respectively.
measure: Progression-Free Survival (PFS)
timeFrame: From first dose of study drug through the data cut-off date of 18 July 2016; median time on follow-up was 14.1, 3.5, 2.6, 16.0, 3.6, and 11.2 months in each group, respectively
Other outcomes:
Locations:
city: Huntsville
country: United States
facility: Clearview Cancer Institute
state: Alabama
city: Burbank
country: United States
facility: Providence St. Joseph's Hospital
state: California
city: Los Angeles
country: United States
facility: David Geffen School of Medicine at UCLA
state: California
city: Salinas
country: United States
facility: Monterey Bay Oncology Corp DBA Pacific Cancer Care
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Tampa
country: United States
facility: H. Lee Moffit Cancer Center & Research Institute
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University Health Melvin and Bren Simon Cancer Center
state: Indiana
city: Bethesda
country: United States
facility: Center for Cancer & Blood Disorders
state: Maryland
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Houston
country: United States
facility: University of Texas M.D. Anderson Cancer Center
state: Texas
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center
state: Washington
city: Milwaukee
country: United States
facility: Froedtert Hospital and the Medical College of Wisconsin
state: Wisconsin
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: