Clinical trial NCT00932698: Study of Oral Ixazomib in Adult Participants With Relapsed and/or Refractory (RR) Multiple Myeloma
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Relapsed and Refractory Multiple Myeloma
Keywords: Relapsed multiple myeloma
Refractory multiple myeloma
Ixazomib Proteasome inhibitor
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2009-07-03
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: The drug being tested in this study is ixazomib. Ixazomib is being tested to treat people who have multiple myeloma. This study will look at the safety and efficacy of ixazomib and will enroll approximately 60 participants.

Participants will receive ixazomib by oral capsule twice weekly on Days 1, 4, 8, and 11 of a 21-day cycle. The study will consist of a dose escalation phase to determine the MTD, followed by an expansion phase in which participants will be treated at the MTD.

This multi-center trial will be conducted in the United States. The overall time to participate in this study is 8 years.

Eligibility criteria: Inclusion Criteria:

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

* Multiple myeloma diagnosed according to the standard criteria.
* Participants with multiple myeloma who have relapsed following at least 2 lines of therapy.
* Participants must have measurable disease.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
* Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
* Male participants 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:

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

* Peripheral neuropathy greater than or equal to (\>=) Grade 2.
* Female participants 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 National Cancer Institute Common Terminology Criteria for Adverse Events (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.
* Corrected QT interval (QTc) \> 470 milliseconds on a 12-lead electrocardiogram (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.

Primary outcomes:
measure: Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)
measure: Number of Participants With Clinically Significant Abnormalities Reported as TEAEs
timeFrame: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)
measure: Number of Participants With a TEAE of Peripheral Neuropathy
timeFrame: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)
measure: Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs
timeFrame: From first dose of the study drug through 30 days after the last dose of study drug or start of subsequent antineoplastic therapy (Up to 81.1 months)
measure: Maximum Tolerated Dose (MTD) of Ixazomib
timeFrame: Cycle 1 (21 days)
measure: Recommended Phase 2 Dose (RP2D) of Ixazomib
timeFrame: Cycle 1 through Cycle 39 (Up to 28.3 months)
Secondary outcomes:
measure: Cmax: Maximum Observed Plasma Concentration for Ixazomib
timeFrame: Cycle 1, Days 1 and 11: Predose and at multiple time points (up to 264 hours) postdose
measure: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
timeFrame: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
measure: AUC(0-last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
timeFrame: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
measure: AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib
timeFrame: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 72 hours) postdose
measure: λz: Terminal Disposition Phase Rate Constant for Ixazomib
timeFrame: Cycle 1, Day 11: predose and at multiple time points (Up to 264 hours) postdose
measure: T1/2: Terminal Disposition Phase Elimination Half-life for Ixazomib
timeFrame: Cycle 1, Day 11: predose and at multiple time points (up to 264 hours) postdose
measure: CL/F: Blood Clearance Calculated Using the Observed Value of the Last Quantifiable Concentration for Ixazomib
timeFrame: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
measure: Emax: Maximum Observed Effect for Ixazomib
timeFrame: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
measure: TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib
timeFrame: Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
measure: Overall Response Rate (ORR)
timeFrame: Cycle 1 through Cycle 115 (Up to 80.1 months)
Other outcomes:
Locations:
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan Comprehensive Cancer Center
state: Michigan
city: Houston
country: United States
facility: M.D. Anderson Cancer Center
state: Texas
Study officials:
affiliation: Millennium Pharmaceuticals, Inc.
name: Medical Monitor
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Richardson PG, Baz R, Wang M, Jakubowiak AJ, Laubach JP, Harvey RD, Talpaz M, Berg D, Liu G, Yu J, Gupta N, Di Bacco A, Hui AM, Lonial S. Phase 1 study of twice-weekly ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma patients. Blood. 2014 Aug 14;124(7):1038-46. doi: 10.1182/blood-2014-01-548826. Epub 2014 Jun 11.