Study of Oral IXAZOMIB in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00932698
First received: July 1, 2009
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

This study will determine the safety profile, tolerability, and maximum tolerated dose (MTD) and disease response of IXAZOMIB administered orally in patients with relapsed and/or refractory multiple myeloma.


Condition Intervention Phase
Relapsed and Refractory Multiple Myeloma
Drug: Oral IXAZOMIB
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Dose-Escalation, Phase 1 Study of the Oral Form of IXAZOMIB (MLN9708), a Second-Generation Proteasome Inhibitor, in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Millennium Pharmaceuticals, Inc.:

Primary Outcome Measures:
  • Number of Adverse events (AEs), serious adverse events (SAEs), assessments of clinical laboratory values, neurotoxicity grading, and vital sign measurements [ Time Frame: From first dose of study drug to 30 days after last dose, upto 13 months ] [ Designated as safety issue: Yes ]
    Safety profile of IXAZOMIB

  • To inform the recommended Phase 2 dose of IXAZOMIB [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
    Phase 2 dose of IXAZOMIB based on both toxicity and efficacy outcomes

  • Number of Adverse events (AEs), serious adverse events (SAEs), assessments of clinical laboratory values, neurotoxicity grading, and vital sign measurements [ Time Frame: From first dose of study drug to the end of 21 days Cycle 1 ] [ Designated as safety issue: Yes ]
    Tolerability and MTD of IXAZOMIB


Secondary Outcome Measures:
  • To characterize the pharmacokinetics (PK) parameters, including, but not limited to, Cmax, Tmax, AUC0-last, AUC0-inf, clearance (CL/F), terminal disposition rate constant, and terminal disposition half-life (t1/2) [ Time Frame: Days 1 and 11 of Cycle 1 ] [ Designated as safety issue: No ]
    Characterization of PK in plasma of orally administered IXAZOMIB

  • To characterize the whole blood 20S proteasome inhibition parameters including, but not limited to, maximum inhibition (Emax) and time of occurrence of Emax (TEmax) [ Time Frame: Days 1 and 11 of Cycle 1 ] [ Designated as safety issue: No ]
    Characterization of the pharmacodynamic effect of IXAZOMIB

  • To determine the overall response rate (CR+PR) and CR+PR+MR rate [ Time Frame: At beginning of Cycle 2 (Day 1) and at the end of treatment up to 12 months or until disease progression ] [ Designated as safety issue: No ]
    To determine the overall response rate (CR+PR) and CR+PR+MR rate of IXAZOMIB in patients with relapsed and/or refractory multiple myeloma and in patients who are either proteasome inhibitor-naïve, have relapsed after VELCADE, or who have recently been treated with carfilzomib


Enrollment: 60
Study Start Date: June 2009
Study Completion Date: March 2013
Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Oral IXAZOMIB Drug: Oral IXAZOMIB
Phase 1: Patients will be administered IXAZOMIB orally on Days 1, 4, 8, and 11 during a 21-day treatment cycle. Doses will increase until a maximum tolerated dose (MTD) is established.

  Eligibility

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

Inclusion Criteria:

Each patient must meet all of the following inclusion criteria to be enrolled in the study:

  • Multiple myeloma diagnosed according to the standard criteria.
  • Patients with multiple myeloma who have relapsed following at least 2 lines of therapy.
  • Patients must have measurable disease.
  • ECOG performance status of 0 to 2.
  • Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
  • Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse.
  • Voluntary written consent.
  • Suitable venous access for study-required blood sampling.

Exclusion Criteria:

Patients meeting any of the following exclusion criteria are not to be enrolled in the study:

  • Peripheral neuropathy > or equal to Grade 2.
  • Female patients who are lactating or have a positive serum pregnancy test during the screening period.
  • Major surgery within 14 days before the first dose of study drug.
  • Infection requiring systemic antibiotic therapy or other serious infection within 14 days before the first dose of study treatment.
  • Life-threatening illness unrelated to cancer.
  • Diarrhea > Grade 1, based on the NCI CTCAE categorization.
  • Systemic antineoplastic or radiation therapy within 14 days of cytotoxic agents within 21 days before the first dose of study treatment.
  • Treatment with any investigational products within 21 days before the first dose of study treatment.
  • Treatment with any investigational proteasome inhibitor.
  • Systemic treatment with prohibited medication.
  • Ongoing therapy with corticosteroids greater than 10mg of prednisone or its equivalent per day. Inhaled and topical steroids are permitted.
  • Central nervous system involvement.
  • Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure, angina, or myocardial infarction within the past 6 months.
  • QTc > 470 milliseconds on a 12-lead ECG obtained during the screening period.
  • Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
  • Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol.
  • Known gastrointestinal (GI) disease or GI procedure that could interfere with the oral absorption of tolerance of IXAZOMIB including difficulty swallowing.
  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: NCT00932698

Locations
United States, Florida
H. Lee Moffitt Cancer Center
Tampa, Florida, United States, 33617
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, Michigan
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States, 48109
United States, Texas
M.D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Millennium Pharmaceuticals, Inc.
Investigators
Study Director: Medical Monitor Millennium Pharmaceuticals, Inc.
  More Information

No publications provided by Millennium Pharmaceuticals, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00932698     History of Changes
Other Study ID Numbers: C16003
Study First Received: July 1, 2009
Last Updated: May 23, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Millennium Pharmaceuticals, Inc.:
Relapsed multiple myeloma
Refractory multiple myeloma
IXAZOMIB Proteasome inhibitor

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
Proteasome Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014