Study of Oral MLN9708 in Adult Patients With Relapsed and/or Refractory Multiple Myeloma - Full Text View

Sponsor:	Millennium Pharmaceuticals, Inc.
Information provided by (Responsible Party):	Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:	NCT00932698

Purpose

This study will determine the safety profile, tolerability, and maximum tolerated dose (MTD) and disease response of MLN9708 administered orally in patients with relapsed and/or refractory multiple myeloma.

Condition	Intervention	Phase
Relapsed and Refractory Multiple Myeloma	Drug: Oral MLN9708	Phase I

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 MLN9708, a Second-Generation Proteasome Inhibitor, in Adult Patients With Relapsed and/or Refractory Multiple Myeloma

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia hemophilia

MedlinePlus related topics: Cancer Multiple Myeloma

U.S. FDA Resources

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 MLN9708
To inform the recommended Phase 2 dose of MLN9708 [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
Phase 2 dose of MLN9708 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 MLN9708

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 MLN9708
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 MLN9708
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 MLN9708 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

Estimated Enrollment:	70
Study Start Date:	October 2009
Estimated Study Completion Date:	July 2013
Estimated Primary Completion Date:	April 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1: Oral MLN9708	Drug: Oral MLN9708 Phase 1: Patients will be administered MLN9708 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 MLN9708 including difficulty swallowing.

Contacts and Locations

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

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:	February 6, 2012
Health Authority:	United States: Food and Drug Administration

Keywords provided by Millennium Pharmaceuticals, Inc.:

Relapsed multiple myeloma
Refractory multiple myeloma
MLN9708
Proteasome inhibitor

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

ClinicalTrials.gov processed this record on February 09, 2012