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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Onyx Pharmaceuticals ( Onyx Therapeutics, Inc. )
ClinicalTrials.gov Identifier:
NCT01881789
First received: June 13, 2013
Last updated: June 24, 2015
Last verified: June 2015
  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:
  • Maximum Tolerated Dose (MTD) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    For each dosing schedule, the MTD will be defined as the highest dose at which a DLT is observed in fewer than 2 of 6 patients. DLT is defined as any of the following treatment-related events occurring in the first 28 days of treatment.

  • Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
    Safety and tolerability of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide, as defined by the type, incidence, severity, and outcome of Adverse Events (AEs).

  • Overall Response Rate (ORR) [ Time Frame: 14 months ] [ Designated as safety issue: No ]
    The antitumor activity of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide, as measured by overall response rate (ORR).

  • Complete Response Rate (CRR) [ Time Frame: 17 months ] [ Designated as safety issue: No ]
    The antitumor activity of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide, as measured by complete response rate (CRR).


Secondary Outcome Measures:
  • Population Pharmacokinetic (PK) Parameters - Apparent Clearance [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    The Apparent Clearance is defined as the amount of drug administered (dose) divided by the plasma concentration-time curve (AUC) of oprozomib and its metabolites at various time points.

  • Population Pharmacokinetic (PK) Parameters - Volume of Distribution [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    The Volume of Distribution is defined as the amount of oprozomib administered (dose) divided by initial oprozomib plasma concentration.

  • Duration of Response (DOR) [ Time Frame: 42 months ] [ Designated as safety issue: No ]
    Duration of Response is defined as the time from first evidence of partial response (PR) or better to confirmation of disease progression or death due to any cause.

  • Progression-Free Survival (PFS) [ Time Frame: 42 months ] [ Designated as safety issue: No ]
    Progression-Free Survival is defined as the time from the start of treatment to disease progression or death (due to any cause), whichever comes first.


Estimated Enrollment: 134
Study Start Date: August 2013
Estimated Primary Completion Date: October 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, 2, 8, 9, 15,16, 22 and 23 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 extended release (ER) Tablets (hereafter referred to as oprozomib) administered orally, once daily on 1, 2, 8, 9, 15,16, 22 and 23 of 28-day cycles
Other Name: Oprozomib ER 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, 2, 8, 9, 15, 16, 22 and 23 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 extended release (ER) Tablets (hereafter referred to as oprozomib) administered orally, once daily on 1, 2, 8, 9, 15,16, 22 and 23 of 28-day cycles
Other Name: Oprozomib ER 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
  • 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
  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

Locations
United States, Alabama
Clearview Cancer Institute
Huntsville, Alabama, United States
United States, California
Providence St. Joseph's Hospital
Burbank, California, United States
David Geffen School of Medicine at UCLA
Los Angeles, California, United States
Monterey Bay Oncology Corp DBA Pacific Cancer Care
Salinas, California, United States
United States, Colorado
Colorado Blood Cancer Institute
Denver, Colorado, United States
United States, Florida
H. Lee Moffit Cancer Center & Research Institute
Tampa, Florida, United States
United States, Illinois
University of Chicago Medical Center
Chicago, Illinois, United States
United States, Indiana
Indiana University Health Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States
United States, Maryland
Center for Cancer & Blood Disorders
Bethesda, Maryland, United States
United States, North Carolina
The University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, United States
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States
United States, Texas
University of Texas M.D. Anderson Cancer Center
Houston, Texas, United States
United States, Washington
Fred Hutchinson Cancer Research Center
Seattle, Washington, United States
United States, Wisconsin
Froedtert Hospital and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States
Sponsors and Collaborators
Onyx Therapeutics, Inc.
Investigators
Study Director: David Ramies, 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 24, 2015
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
Blood Protein Disorders
Cardiovascular Diseases
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Immune System Diseases
Immunoproliferative Disorders
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Paraproteinemias
Vascular Diseases
BB 1101
Cyclophosphamide
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Lenalidomide
Thalidomide
Alkylating Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antiemetics
Antineoplastic Agents
Antineoplastic Agents, Alkylating

ClinicalTrials.gov processed this record on September 02, 2015