Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Infective Agents

Antineoplastic Agents

All Drugs and Chemicals

Thalidomide

Lenalidomide

Bortezomib

Ixazomib

Proteasome Inhibitors

HIV Protease Inhibitors

Protease Inhibitors

Enzyme Inhibitors

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).

Medical Monitor

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.

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.

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

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.

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.

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.

Neurotoxicity was assessed as the number of participants with the TEAE of peripheral neuropathy.

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.

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.

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.

CL/F is apparent clearance of the drug from the plasma.

Emax was determined to characterize the whole blood 20S proteasome inhibition parameters.

TEmax was determined to characterize the whole blood 20S proteasome inhibition parameters.

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.

Millennium Pharmaceuticals, Inc.

At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment.

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 2.0 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

Total

Age, Continuous

Sex: Female, Male

Race/Ethnicity, Customized

United States

Region of Enrollment

Here, number analyzed are the participants who were evaluated for this baseline measure.

Height

Weight

Body Surface Area (m\^2)=\[Height(cm) \* Weight (kg)\]/3600)\^1/2.

Body Surface Area

Time Since Primary Diagnosis to First Dose

Safety population included all participants who received at least 1 dose of ixazomib. A total of 60 participants participated in the study. There were 7 participants in Dose Escalation Cohort 6: Ixazomib 2.0 mg/m\^2 arm group, 6 out of 7 participated in both phases of the study and were counted once in the expansion cohort.

Medical Director

SAEs

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 determine 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.

Safety population included all participants who received at least 1 dose of ixazomib.

Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

Blood Creatinine Increased

Blood Urea Increased

White Blood Cell Count Decreased

Neutrophil Count Decreased

Alanine Aminotransferase Increased

Liver Function Test Increased

Blood Calcium Increased

Platelet Count Decreased

Haematocrit Decreased

Haemoglobin Decreased

Number of Participants With Clinically Significant Abnormalities Reported as TEAEs

Neuropathy Peripheral

Peripheral Sensory Neuropathy

Number of Participants With a TEAE of Peripheral Neuropathy

Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs

All participants who received ixazomib 0.24 mg/m\^2, 0.48 mg/m\^2, 0.8 mg/m\^2, 1.2 mg/m\^2, 1.68 mg/m\^2, 2 mg/m\^2 or 2.23 mg/m\^2 in dose-escalation cohorts.

Ixazomib (All Groups)

DLT-evaluable population was defined as all participants who received all Cycle 1 doses of ixazomib and completed Cycle 1 or who experienced DLT in Cycle 1.

Maximum Tolerated Dose (MTD) of Ixazomib

Recommended Phase 2 Dose (RP2D) of Ixazomib

Day 1

Day 11

PK population was defined as all participants who had sufficient dosing data and ixazomib concentration-time data to permit calculation of ixazomib PK parameters. Number analyzed is the number of participants with data available for analysis at the given time-point.

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 was not reported as this PK parameter could not be calculated.

CL/F: Blood Clearance Calculated Using the Observed Value of the Last Quantifiable Concentration for Ixazomib

Ixazomib (MLN9708) 2 mg/m\^2 (MTD), capsule, orally, twice weekly on Days 1, 4, 8 and 11 in 21-day treatment cycles until PD or unacceptable toxicity in participants with relapsed multiple myeloma previously treated with VELCADE during Part 2 (dose expansion cohort) of the study.

VELCADE-Relapsed Expansion Cohort: MLN9708 2.0 mg/m^2

No data is reported due to concerns about the third-party laboratory's performance of the 20S assay that precluded the ability to confirm the accuracy of the data generated. The data was not considered reliable.

Emax: Maximum Observed Effect for Ixazomib

TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib

CR+PR

CR+PR+MR

Response-evaluable population included participants who received at least 1 dose of study drug, had measurable disease at baseline, and at least 1 post baseline disease assessment.

Spots Global Cancer Trial Database for Study of Oral Ixazomib in Adult Participants With Relapsed and/or Refractory (RR) Multiple Myeloma

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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