Clinical trial NCT01416428: Open-label Study of the Safety and Activity of Oprozomib in Patients With Hematologic Malignancies
Official title: Phase 1b/2, Multicenter, Open-label Study of the Safety and Activity of Oprozomib in Patients With Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Waldenstrom Macroglobulinemia
Keywords: multiple myeloma
waldenstrom macroglobulinemia
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2011-08-15
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the maximum tolerated dose (MTD), activity, and safety of oprozomib in patients with hematologic malignancies.


Eligibility criteria: INCLUSION CRITERIA:

Phase 1b

* Histologically confirmed diagnosis of a hematologic malignancy, excluding patients with acute leukemia or MDS.
* Relapsed after standard therapy for their malignancy and considered to be an appropriate candidate for a Phase 1 clinical study by their treating physician.

Phase 2

* Multiple myeloma with measurable disease
* Waldenström macroglobulinemia with symptomatic relapse
* Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.

Ethical/Other

* Patients must sign a written informed consent form in accordance with federal, local, and institutional guidelines.
* Female patients of childbearing potential must have a negative serum or urine pregnancy test and agree to use effective contraception. Male patients must use an effective barrier method of contraception.

EXCLUSION CRITERIA:

* Chemotherapy with approved or investigational anticancer therapeutics, including steroid therapy intended to treat underlying malignancy, within 3 weeks prior to first dose or 6 weeks for antibody therapy.
* Radiation therapy within 3 weeks prior to first dose. Radioimmunotherapy within 8 weeks prior to first dose. Localized radiation therapy within 1 week prior to first dose.
* Immunotherapy within 3 weeks prior to first dose (except for antibody therapy, where 6 weeks is required).
* Prior stem cell transplant (SCT) therapy (autologous SCT within the prior 8 weeks; allogeneic SCT within the prior 16 weeks). Patients with prior allogeneic SCT should not have evidence of moderate-to-severe graft-vs-host disease (GvHD; as defined in Filipovich 2005).
* Evidence of central nervous system (CNS) lymphoma.
* Prior treatment with carfilzomib unless in the phase 2.
* Major surgery within 3 weeks prior to first dose.
* Symptomatic Congestive heart failure, ischemia, conduction abnormalities, or myocardial infarction within 6 months.
* Acute active infection requiring systemic antibiotics, antivirals, or antifungals.
* Known or suspected human immunodeficiency virus (HIV) infection or patients who are HIV seropositive.
* Active hepatitis A, B, or C infection.
* Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose.
* Patients with pleural effusions requiring routine thoracentesis or ascites requiring routine paracentesis.
* History of previous clinically significant GI bleed in the last 6 months prior to first dose.
* Female patients who are pregnant or lactating.

Primary outcomes:
measure: Determine the MTD (Phase 1) and ORR (Phase 2).
timeFrame: 6 weeks to 18 months
Secondary outcomes:
measure: Evaluate the duration of response (DOR)
timeFrame: 64 months
measure: Estimate the clinical benefit response (CBR)
timeFrame: 64 months
measure: Estimate the major response for Waldenström macroglobulinemia (WM)
timeFrame: 64 months
measure: Evaluate progression-free survival (PFS) for multiple myeloma (MM) subjects
timeFrame: 64 months
measure: Evaluate the PFS for Waldenström macroglobulinemia (WM) subjects
timeFrame: 64 months
measure: PK parameters - maximum plasma concentration (Cmax)
timeFrame: 55 months
measure: PK parameters - time of maximum plasma concentration (tmax)
timeFrame: 55 months
measure: PK parameters - plasma concentration-time curve (AUC)
timeFrame: 55 months
measure: Assess renal elimination of oprozomib and its metabolites (Phase 1b only)
timeFrame: 55 months
measure: Change from Baseline in hematology laboratory results
timeFrame: 64 months
measure: Change from Baseline in serum chemistry results
timeFrame: 64 months
measure: Change from Baseline in vital signs
timeFrame: 64 months
measure: Change from Baseline in weight
timeFrame: 64 months
measure: Evaluate safety of oprozomib in Phase 2
timeFrame: Until 30 days after the end of study (64 months)
measure: Assess the effect on transfusion/ red blood cell (RBC) growth factor requirements (Phase 2 only) for WM only
timeFrame: 64 months
measure: Assess the effect on plasmapheresis requirements (Phase 2 only) for WM only
timeFrame: 64 months
measure: Assess the effect on lymphoplasmacytic cells in the bone marrow (Phase 2 only) for WM only
timeFrame: 64 months
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Mayo Clinic Scottsdale
state: Arizona
city: Salinas
country: United States
facility: Pacific Cancer Care
state: California
city: Denver
country: United States
facility: Colorado Blood Cancer Institute
state: Colorado
city: Jacksonville
country: United States
facility: Mayo Clinic
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland, Greenebaum Cancer Center
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Boston
country: United States
facility: Mass General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: Virginia Piper Cancer Institute
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University School of Medicine Division of Oncology
state: Missouri
city: Hackensack
country: United States
facility: John Theurer Cancer Center at Hackensack University
state: New Jersey
city: Morristown
country: United States
facility: Hematology Oncology of Northern New Jersey
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology
state: New York
city: New York
country: United States
facility: Mount Sinai Medical Center
state: New York
city: Nashville
country: United States
facility: Sarah Cannon Research Institute / Tennessee Oncology, PLLC
state: Tennessee
city: Kennewick
country: United States
facility: Columbia Basin Hematology and Oncology
state: Washington
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: