Study of Oral Ixazomib in Adult Participants With Relapsed and/or Refractory (RR) Multiple Myeloma
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
2 other identifiers
interventional
60
1 country
5
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Oct 2009
Longer than P75 for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
July 1, 2009
CompletedFirst Posted
Study publicly available on registry
July 3, 2009
CompletedStudy Start
First participant enrolled
October 12, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 20, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
May 23, 2017
CompletedResults Posted
Study results publicly available
August 7, 2019
CompletedAugust 7, 2019
June 1, 2019
3.7 years
July 1, 2009
October 24, 2018
June 19, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (6)
Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a participant administered a medicinal investigational drug. The untoward medical occurrence does not necessarily have to have a causal relationship with treatment. An SAE is any untoward medical occurrence that results in death;is life-threatening;requires inpatient hospitalization or prolongation of present hospitalization;results in persistent or significant disability/incapacity;is a congenital anomaly/birth defect;or is a medically important event that may not be immediately life-threatening or result in death or hospitalization, but may jeopardize the participant or may require intervention to prevent one of other outcomes listed in definition above, or involves suspected transmission via a medicinal product of an infectious agent. A TEAE is defined as an AE that occurs after administration of first dose of study drug and through 30 days after last dose of study drug or until start of subsequent antineoplastic therapy.
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)
Number of Participants With Clinically Significant Abnormalities Reported as TEAEs
The number of participants with any clinically significant abnormal standard safety laboratory values collected throughout the study reported as TEAEs. Parameters assessed were hematology, serum chemistry and urinalysis.
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)
Number of Participants With a TEAE of Peripheral Neuropathy
Neurotoxicity was assessed as the number of participants with the TEAE of peripheral neuropathy.
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)
Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs
The number of participants with any clinically significant changes in vital signs collected throughout the study that were reported as TEAEs. Measurement of vital signs, included oral temperature, blood pressure, and heart rate.
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)
Maximum Tolerated Dose (MTD) of Ixazomib
MTD was highest dose of Ixazomib, at which \<=1 of 6 participants experienced dose-limiting toxicity (DLT) during Cycle 1 of Phase 1. DLT was defined as any of following considered possibly related to therapy: Grade 4 neutropenia (absolute neutrophil count \[ANC\] \<500 cell per cubic millimeter \[cells/mm\^3\]) for \>7 days;Grade 3 neutropenia with fever or infection; Grade 4 thrombocytopenia (platelets \< 25,000/mm\^3) for \>7 days;Grade 3 thrombocytopenia with clinically significant bleeding; platelet count \<10,000/mm\^3; Grade 2 peripheral neuropathy with pain or \>=Grade 3 peripheral neuropathy; \>=Grade 3 nausea/emesis, diarrhea controlled by supportive therapy; Grade 3 QTc prolongation (QTc \>500 millisecond \[msec\]);any \>=Grade 3 nonhematologic toxicity except Grade 3 arthralgia/myalgia; or \<1 week Grade 3 fatigue; delay in initiation of the subsequent therapy cycle by \>2 weeks; other \>=Grade 2 study drug-related nonhematologic toxicities requiring therapy discontinuation.
Cycle 1 (21 days)
Recommended Phase 2 Dose (RP2D) of Ixazomib
The RP2D of Ixazomib was determined in Part 1 (dose escalation) on the basis of the totality of safety, tolerability, pharmacokinetics (PK) and pharmacodynamic data observed in Cycle 1 and beyond.
Cycle 1 through Cycle 39 (Up to 28.3 months)
Secondary Outcomes (10)
Cmax: Maximum Observed Plasma Concentration for Ixazomib
Cycle 1, Days 1 and 11: Predose and at multiple time points (up to 264 hours) postdose
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
AUC(0-last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib
Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 72 hours) postdose
λz: Terminal Disposition Phase Rate Constant for Ixazomib
Cycle 1, Day 11: predose and at multiple time points (Up to 264 hours) postdose
- +5 more secondary outcomes
Study Arms (11)
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2
EXPERIMENTALIxazomib 0.24 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 220 days).
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2
EXPERIMENTALIxazomib 0.48 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 270 days).
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2
EXPERIMENTALIxazomib 0.8 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 137 days).
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2
EXPERIMENTALIxazomib 1.2 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1436 days).
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2
EXPERIMENTALIxazomib 1.68 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 456 days).
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2
EXPERIMENTALIxazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 1621 days).
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2
EXPERIMENTALIxazomib 2.23 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months (Up to 2434 days).
Relapsed and Refractory Expansion Cohort: Ixazomib 2 mg/m^2
EXPERIMENTALIxazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months, Participants must also be refractory to their most recent therapy as evidenced by PD while on therapy or within 60 days after their last dose of therapy (Up to 1621 days).
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2
EXPERIMENTALIxazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after \>=1 prior therapy but have relapsed after previous Velcade exposure and were not treated with any other proteasome inhibitors (Up to 1573 days).
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2
EXPERIMENTALIxazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants with relapsed or refractory disease after \>=1 prior therapy which must include thalidomide (or lenalidomide) and corticosteroid, but who never received a proteasome inhibitor (Up to 550 days).
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2
EXPERIMENTALIxazomib 2.0 mg/m\^2, capsule, orally, on Days 1, 4, 8 and 11 during a 21-day treatment cycle until progressive disease (PD) or unacceptable toxicity up to 12 months unless the investigator and sponsor determined the participant would benefit from therapy beyond 12 months. Participants who previously received carfilzomib and had relapsed or refractory disease (Up to 123 days).
Interventions
Ixazomib capsules
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (5)
H. Lee Moffitt Cancer Center
Tampa, Florida, 33617, United States
Emory University
Atlanta, Georgia, 30322, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, 48109, United States
M.D. Anderson Cancer Center
Houston, Texas, 77030, United States
Related Publications (2)
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.
PMID: 28803351DERIVEDRichardson 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.
PMID: 24920586DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- Medical Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Monitor
Millennium Pharmaceuticals, Inc.
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
July 1, 2009
First Posted
July 3, 2009
Study Start
October 12, 2009
Primary Completion
June 20, 2013
Study Completion
May 23, 2017
Last Updated
August 7, 2019
Results First Posted
August 7, 2019
Record last verified: 2019-06
Data Sharing
- IPD Sharing
- Will share
Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.