search
Back to results

Study of Oral Ixazomib in Adult Participants With Relapsed and/or Refractory (RR) Multiple Myeloma

Primary Purpose

Relapsed and Refractory Multiple Myeloma

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ixazomib
Sponsored by
Millennium Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Relapsed and Refractory Multiple Myeloma focused on measuring Relapsed multiple myeloma, Refractory multiple myeloma, Ixazomib Proteasome inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • H. Lee Moffitt Cancer Center
  • Emory University
  • Dana-Farber Cancer Institute
  • University of Michigan Comprehensive Cancer Center
  • M.D. Anderson Cancer Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2

Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2

Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2

Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2

Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2

Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2

Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2

Relapsed and Refractory Expansion Cohort: Ixazomib 2 mg/m^2

Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2

Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2

Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2

Arm Description

Ixazomib 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).

Ixazomib 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).

Ixazomib 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).

Ixazomib 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).

Ixazomib 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).

Ixazomib 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).

Ixazomib 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).

Ixazomib 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).

Ixazomib 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).

Ixazomib 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).

Ixazomib 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).

Outcomes

Primary Outcome Measures

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.
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.
Number of Participants With a TEAE of Peripheral Neuropathy
Neurotoxicity was assessed as the number of participants with the TEAE of peripheral neuropathy.
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.
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.
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.

Secondary Outcome Measures

Cmax: Maximum Observed Plasma Concentration for Ixazomib
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
AUC(0-last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib
λz: Terminal Disposition Phase Rate Constant for Ixazomib
T1/2: Terminal Disposition Phase Elimination Half-life for Ixazomib
CL/F: Blood Clearance Calculated Using the Observed Value of the Last Quantifiable Concentration for Ixazomib
CL/F is apparent clearance of the drug from the plasma.
Emax: Maximum Observed Effect for Ixazomib
Emax was determined to characterize the whole blood 20S proteasome inhibition parameters.
TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib
TEmax was determined to characterize the whole blood 20S proteasome inhibition parameters.
Overall Response Rate (ORR)
ORR is defined as percentage of participants with complete response (CR) or partial response (PR) or minimal response (MR) as assessed by the investigator using International Myeloma Working Group Uniform Response criteria. CR=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. PR=≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg /24 h. MR=25-49% reduction in the serum monoclonal paraprotein maintained for a minimum of 6 weeks; 50-89% reduction in 24-h urinary light chain excretion, which still exceeds 200 mg/24 h, maintained for a minimum of 6 weeks; for participants with non-secretory myeloma only, 25-49% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy, if biopsy is performed, maintained for a minimum of 6 weeks; 25-49% reduction in the size of soft tissue plasmacytomas; no increase in the size or number of lytic bone lesions.

Full Information

First Posted
July 1, 2009
Last Updated
June 19, 2019
Sponsor
Millennium Pharmaceuticals, Inc.
search

1. Study Identification

Unique Protocol Identification Number
NCT00932698
Brief Title
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

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
October 12, 2009 (Actual)
Primary Completion Date
June 20, 2013 (Actual)
Study Completion Date
May 23, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Millennium Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed and Refractory Multiple Myeloma
Keywords
Relapsed multiple myeloma, Refractory multiple myeloma, Ixazomib Proteasome inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2
Arm Type
Experimental
Arm Description
Ixazomib 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).
Arm Title
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2
Arm Type
Experimental
Arm Description
Ixazomib 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).
Arm Title
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2
Arm Type
Experimental
Arm Description
Ixazomib 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).
Arm Title
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2
Arm Type
Experimental
Arm Description
Ixazomib 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).
Arm Title
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2
Arm Type
Experimental
Arm Description
Ixazomib 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).
Arm Title
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2
Arm Type
Experimental
Arm Description
Ixazomib 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).
Arm Title
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2
Arm Type
Experimental
Arm Description
Ixazomib 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).
Arm Title
Relapsed and Refractory Expansion Cohort: Ixazomib 2 mg/m^2
Arm Type
Experimental
Arm Description
Ixazomib 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).
Arm Title
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2
Arm Type
Experimental
Arm Description
Ixazomib 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).
Arm Title
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2
Arm Type
Experimental
Arm Description
Ixazomib 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).
Arm Title
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2
Arm Type
Experimental
Arm Description
Ixazomib 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).
Intervention Type
Drug
Intervention Name(s)
Ixazomib
Other Intervention Name(s)
MLN9708
Intervention Description
Ixazomib capsules
Primary Outcome Measure Information:
Title
Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
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)
Title
Number of Participants With Clinically Significant Abnormalities Reported as TEAEs
Description
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.
Time Frame
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)
Title
Number of Participants With a TEAE of Peripheral Neuropathy
Description
Neurotoxicity was assessed as the number of participants with the TEAE of peripheral neuropathy.
Time Frame
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)
Title
Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs
Description
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.
Time Frame
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)
Title
Maximum Tolerated Dose (MTD) of Ixazomib
Description
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.
Time Frame
Cycle 1 (21 days)
Title
Recommended Phase 2 Dose (RP2D) of Ixazomib
Description
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.
Time Frame
Cycle 1 through Cycle 39 (Up to 28.3 months)
Secondary Outcome Measure Information:
Title
Cmax: Maximum Observed Plasma Concentration for Ixazomib
Time Frame
Cycle 1, Days 1 and 11: Predose and at multiple time points (up to 264 hours) postdose
Title
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib
Time Frame
Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
Title
AUC(0-last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib
Time Frame
Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
Title
AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib
Time Frame
Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 72 hours) postdose
Title
λz: Terminal Disposition Phase Rate Constant for Ixazomib
Time Frame
Cycle 1, Day 11: predose and at multiple time points (Up to 264 hours) postdose
Title
T1/2: Terminal Disposition Phase Elimination Half-life for Ixazomib
Time Frame
Cycle 1, Day 11: predose and at multiple time points (up to 264 hours) postdose
Title
CL/F: Blood Clearance Calculated Using the Observed Value of the Last Quantifiable Concentration for Ixazomib
Description
CL/F is apparent clearance of the drug from the plasma.
Time Frame
Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
Title
Emax: Maximum Observed Effect for Ixazomib
Description
Emax was determined to characterize the whole blood 20S proteasome inhibition parameters.
Time Frame
Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
Title
TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib
Description
TEmax was determined to characterize the whole blood 20S proteasome inhibition parameters.
Time Frame
Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
Title
Overall Response Rate (ORR)
Description
ORR is defined as percentage of participants with complete response (CR) or partial response (PR) or minimal response (MR) as assessed by the investigator using International Myeloma Working Group Uniform Response criteria. CR=Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. PR=≥50% reduction of serum M-protein and reduction in 24-h urinary M-protein by ≥90% or to <200 mg /24 h. MR=25-49% reduction in the serum monoclonal paraprotein maintained for a minimum of 6 weeks; 50-89% reduction in 24-h urinary light chain excretion, which still exceeds 200 mg/24 h, maintained for a minimum of 6 weeks; for participants with non-secretory myeloma only, 25-49% reduction in plasma cells in a bone marrow aspirate and on trephine biopsy, if biopsy is performed, maintained for a minimum of 6 weeks; 25-49% reduction in the size of soft tissue plasmacytomas; no increase in the size or number of lytic bone lesions.
Time Frame
Cycle 1 through Cycle 115 (Up to 80.1 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Millennium Pharmaceuticals, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
H. Lee Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33617
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
University of Michigan Comprehensive Cancer Center
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Facility Name
M.D. Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
Citations:
PubMed Identifier
28803351
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.
Results Reference
derived
PubMed Identifier
24920586
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.
Results Reference
derived

Learn more about this trial

Study of Oral Ixazomib in Adult Participants With Relapsed and/or Refractory (RR) Multiple Myeloma

We'll reach out to this number within 24 hrs