Study Evaluating the Safety and Tolerability of Weekly Dosing of Oral IXAZOMIB in Adult Patients With Relapsed and Refractory Multiple Myeloma

NCT ID: NCT00963820

Last Updated: 2018-01-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-10-31
• Study Completion Date: 2014-01-31

Brief Summary

The primary objective of this study is to determine the safety profile, tolerability, and maximum tolerated dose of ixazomib citrate (MLN9708) when taken orally on a weekly dosing schedule by patients with relapsed and refractory multiple myeloma (RRMM). Secondary objectives include pharmacokinetics and response rates.

Detailed Description

The drug being tested in this study is called ixazomib citrate (MLN9708). Ixazomib citrate is being tested for people who have multiple myeloma who have relapsed after treatment or become unresponsive to treatment.

This study will determine the maximum tolerated dose (MTD) of ixazomib citrate using a dose escalation scheme. Once MTD is established, participants will be enrolled at MTD into one of the 4 expansion cohorts to characterize the safety, tolerability and efficacy of MLN9708. Blood samples for safety labs, hematology, serum chemistry and pharmacokinetic evaluations will be obtained at the timepoints specified. Disease response assessment is to be performed on the first day of every other cycle beginning with Cycle 3.

The study will enroll approximately 60 patients. All participants will receive treatment with ixazomib citrate. This multi-center trial will be conducted in the United States. The overall time to participate in this study is up to 60 days, and participants will make 12-16 visits to the clinic for study procedures.

Conditions

Multiple Myeloma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1.68 mg/m^2

Ixazomib citrate, 1.68 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Group Type: EXPERIMENTAL

Ixazomib citrate

Intervention Type: DRUG

Ixazomib citrate capsules

2.23 mg/m^2

Ixazomib citrate, 2.23 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Group Type: EXPERIMENTAL

Ixazomib citrate

Intervention Type: DRUG

Ixazomib citrate capsules

2.97 mg/m^2

Ixazomib citrate, 2.97 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Group Type: EXPERIMENTAL

Ixazomib citrate

Intervention Type: DRUG

Ixazomib citrate capsules

3.95 mg/m^2

Ixazomib citrate, 3.95 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Group Type: EXPERIMENTAL

Ixazomib citrate

Intervention Type: DRUG

Ixazomib citrate capsules

Relapsed and Refractory (RR)

Ixazomib citrate, 2.97 mg/m\^2 established Maximum Tolerated Dose (MTD), capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the Relapsed and Refractory (RR) expansion cohort. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Group Type: EXPERIMENTAL

Ixazomib citrate

Intervention Type: DRUG

Ixazomib citrate capsules

VELCADE-Relapsed (VR)

Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the VELCADE-relapsed (VR) expansion cohort. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Group Type: EXPERIMENTAL

Ixazomib citrate

Intervention Type: DRUG

Ixazomib citrate capsules

PI naïve

Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in expansion cohort of participants who were proteasome inhibitor-naïve (PI naïve). All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Group Type: EXPERIMENTAL

Ixazomib citrate

Intervention Type: DRUG

Ixazomib citrate capsules

Carfilzomib

Ixazomib citrate, 2.97 mg/m\^2 established MTD, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the expansion cohort of participants who received their last dose of carfilzomib between 21 and 60 days prior to the first dose of ixazomib citrate. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Group Type: EXPERIMENTAL

Ixazomib citrate

Intervention Type: DRUG

Ixazomib citrate capsules

0.24 mg/m^2

Ixazomib citrate, 0.24 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate

Group Type: EXPERIMENTAL

Ixazomib citrate

Intervention Type: DRUG

Ixazomib citrate capsules

0.48 mg/m^2

Ixazomib citrate, 0.48 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Group Type: EXPERIMENTAL

Ixazomib citrate

Intervention Type: DRUG

Ixazomib citrate capsules

0.80 mg/m^2

Ixazomib citrate, 0.80 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period. All dose amounts are expressed as the dose of ixazomib, the biologically active moiety of ixazomib citrate.

Group Type: EXPERIMENTAL

Ixazomib citrate

Intervention Type: DRUG

Ixazomib citrate capsules

1.20 mg/m^2

Ixazomib citrate, 1.20 mg/m\^2, capsules, orally, once weekly on Days 1, 8, and 15 of a 28-day cycle in the dose escalation period.

Group Type: EXPERIMENTAL

Ixazomib citrate

Intervention Type: DRUG

Ixazomib citrate capsules

Interventions

Ixazomib citrate

Ixazomib citrate capsules

Intervention Type: DRUG

Other Intervention Names

MLN9708

Eligibility Criteria

Inclusion Criteria

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

• Adult patients with multiple myeloma who have relapsed following at least 2 lines of therapy.
• Patients must have measurable disease.
• Appropriate functional status, including the recovery from the effects of prior antineoplastic therapy, and acceptable organ function as described in the protocol.
• 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.
• Willing and able to give written informed consent.
• Suitable venous access for study-required blood sampling.

Exclusion Criteria

• Peripheral neuropathy that is greater or equal to Grade 2.
• Major surgery or, serious infections, or infections that required systemic antibiotic therapy within 14 days before the first dose of study drug.
• Life-threatening illness unrelated to cancer.
• Diarrhea that is greater than Grade 1 as outlined in the protocol
• Systemic antineoplastic or radiation therapy within 14 days or cytotoxic agents, or 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 medications that are outlined in the protocol within 14 days of study treatment.
• Ongoing therapy with corticosteroids greater than 10mg of prednisone or its equivalent per day.
• 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.
• Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Millennium Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Monitor

Role: STUDY_DIRECTOR

Millennium Pharmaceuticals, Inc.

Locations

Mayo Clinic- Scottsdale

Scottsdale, Arizona, United States

James R. Berenson, MD, Inc

West Hollywood, California, United States

University of Chicago

Chicago, Illinois, United States

Mayo Clinic

Rochester, Minnesota, United States

Weill-Cornell Medical College

New York, New York, United States

Fred Hutchinson Cancer Research Center

Seattle, Washington, United States

Countries

United States

References

Gupta N, Yang H, Hanley MJ, Zhang S, Liu R, Kumar S, Richardson PG, Skacel T, Venkatakrishnan K. Dose and Schedule Selection of the Oral Proteasome Inhibitor Ixazomib in Relapsed/Refractory Multiple Myeloma: Clinical and Model-Based Analyses. Target Oncol. 2017 Oct;12(5):643-654. doi: 10.1007/s11523-017-0524-3.

Reference Type: DERIVED

PMID: 28803351 (View on PubMed)

Kumar SK, Bensinger WI, Zimmerman TM, Reeder CB, Berenson JR, Berg D, Hui AM, Gupta N, Di Bacco A, Yu J, Shou Y, Niesvizky R. Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma. Blood. 2014 Aug 14;124(7):1047-55. doi: 10.1182/blood-2014-01-548941. Epub 2014 Jun 5.

Reference Type: DERIVED

PMID: 24904120 (View on PubMed)

Other Identifiers

U1111-1166-8401

Identifier Type: OTHER

Identifier Source: secondary_id

C16004

Identifier Type: -

Identifier Source: org_study_id