Study of Oprozomib and Dexamethasone, in Combination With Lenalidomide or Oral Cyclophosphamide in Patients With Newly Diagnosed Multiple Myeloma

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Onyx Pharmaceuticals
Sponsor:
Information provided by (Responsible Party):
Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier:
NCT01881789
First received: June 13, 2013
Last updated: June 4, 2014
Last verified: June 2014
  Purpose

Phase 1b:

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

Phase 2:

  • To estimate the overall response rate (ORR) and complete response rate (CRR)
  • To evaluate the safety and tolerability of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide

Secondary Objectives:

  • To evaluate population pharmacokinetic (PK) parameter estimates of oprozomib and variability in these estimates when administered in combination with dexamethasone and lenalidomide or oral cyclophosphamide
  • To estimate the duration of response (DOR)
  • To estimate progression-free survival (PFS)

Condition Intervention Phase
Multiple Myeloma
Drug: Oprozomib
Drug: Lenalidomide
Drug: Dexamethasone
Drug: Cyclophosphamide
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Onyx Pharmaceuticals:

Primary Outcome Measures:
  • To establish the maximum tolerated dose (MTD) of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • To evaluate the safety and tolerability of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
  • To estimate the overall response rate (ORR) [ Time Frame: 14 months ] [ Designated as safety issue: No ]
  • To estimate the complete response rate (CRR) [ Time Frame: 17 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate population pharmacokinetic (PK) parameter estimates of oprozomib and variability in these estimates when administered in combination with lenalidomide and dexamethasone, or oral cyclophosphamide and dexamethasone [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    Based on plasma concentration of oprozomib and its metabolites at various time points

  • To estimate the duration of response (DOR) [ Time Frame: 42 months ] [ Designated as safety issue: No ]
  • To estimate progression-free survival (PFS) [ Time Frame: 42 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 118
Study Start Date: August 2013
Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Oprozomib, Lenalidomide and Dexamethasone (ORd)
Subjects will receive oprozomib administered orally, once daily on Days 1-5 and on Days 15-19 in combination with lenalidomide at a dose of 25 mg on Days 1-21, and dexamethasone at a dose of 20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23 of 28-day cycles
Drug: Oprozomib
Subjects will receive Oprozomib Tablets (hereafter referred to as oprozomib) administered orally, once daily on Days 1-5 and on Days 15-19 of 28 day cycles
Other Name: Oprozomib tablets
Drug: Lenalidomide
Subjects will receive lenalidomide 25 mg on Days 1-21 of 28 day cycles
Other Name: Revlimid
Drug: Dexamethasone
Subjects will receive dexamethasone 20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23 of 28 day cycles
Experimental: Oprozomib, Cyclophosphamide and Dexamethasone (OCyd)
Subjects will receive oprozomib administered orally, once daily on Days 1-5 and on Days 15-19 in combination with oral cyclophosphamide at a dose of 300 mg/m2 on Days 1, 8, and 15, and dexamethasone at a dose of 20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23 of 28-day cycles
Drug: Oprozomib
Subjects will receive Oprozomib Tablets (hereafter referred to as oprozomib) administered orally, once daily on Days 1-5 and on Days 15-19 of 28 day cycles
Other Name: Oprozomib tablets
Drug: Dexamethasone
Subjects will receive dexamethasone 20 mg on Days 1, 2, 8, 9, 15, 16, 22, and 23 of 28 day cycles
Drug: Cyclophosphamide
Subjects will receive cyclophophamide 300 mg/m2 on Days 1, 8 and 15 of 28 day cycles
Other Name: Cytoxan

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Newly diagnosed, symptomatic multiple myeloma patients for whom treatment is indicated per the 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
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01881789

Contacts
Contact: Onyx Medical Information 877-669-9121 medinfo@onyx.com

Locations
United States, California
Providence St. Joseph's Hospital Recruiting
Burbank, California, United States
United States, Colorado
Colorado Blood Cancer Institute Recruiting
Denver, Colorado, United States
United States, Indiana
Indiana University Health Melvin and Bren Simon Cancer Center Recruiting
Indianapolis, Indiana, United States
United States, Ohio
Cleveland Clinic Recruiting
Cleveland, Ohio, United States
United States, Texas
University of Texas M.D. Anderson Cancer Center Recruiting
Houston, Texas, United States
United States, Washington
Fred Hutchinson Cancer Research Center Recruiting
Seattle, Washington, United States
United States, Wisconsin
Froedtert Hospital and the Medical College of Wisconsin Recruiting
Milwaukee, Wisconsin, United States
Sponsors and Collaborators
Onyx Therapeutics, Inc.
Investigators
Study Director: Paula O'Connor, MD Onyx Therapeutics, Inc.
  More Information

No publications provided

Responsible Party: Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier: NCT01881789     History of Changes
Other Study ID Numbers: OPZ003
Study First Received: June 13, 2013
Last Updated: June 4, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Onyx Pharmaceuticals:
multiple myeloma
proteasome inhibitor
oprozomib
orpozomib tablets

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Thalidomide
Lenalidomide
Dexamethasone
Dexamethasone acetate
Dexamethasone 21-phosphate
BB 1101
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 22, 2014