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NCT00932698

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

Completed Phase 1 Results posted Last updated 7 August 2019
What this trial tests

Phase 1 trial testing Ixazomib in Relapsed and Refractory Multiple Myeloma in 60 participants. Completed in 23 May 2017.

Timeline
12 October 2009
Primary endpoint
20 June 2013
23 May 2017

Quick facts

Lead sponsorMillennium Pharmaceuticals, Inc.
PhasePhase 1
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment60
Start date12 October 2009
Primary completion20 June 2013
Estimated completion23 May 2017
Sites5 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

Millennium Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Relapsed and Refractory Multiple Myeloma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

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

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 jeopard

AEs
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^23
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^23
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^23
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^23
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^23
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^27
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^24
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^220
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^212
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^26
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^22
SAEs
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^20
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^20
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^22
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^22
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^25
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^23
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^214
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^26
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^23
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^22
Number of Participants With Clinically Significant Abnormalities Reported as TEAEs Primary · 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)

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.

Blood Creatinine Increased
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^21
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^21
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^21
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^21
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^21
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^22
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^22
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20
Blood Urea Increased
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^20
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^20
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^20
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^20
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^20
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^20
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^21
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^21
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20
White Blood Cell Count Decreased
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^20
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^20
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^20
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^21
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^20
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^21
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^20
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^20
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20
Neutrophil Count Decreased
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^20
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^20
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^20
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^20
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^21
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^20
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^21
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20
Alanine Aminotransferase Increased
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^20
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^20
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^20
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^20
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^20
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^21
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^20
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20
Liver Function Test Increased
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^20
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^20
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^20
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^20
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^20
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^21
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^20
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20
Blood Calcium Increased
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^20
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^20
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^21
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^20
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^20
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^20
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^20
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20
Platelet Count Decreased
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^20
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^20
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^20
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^20
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^21
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^20
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^20
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20
Number of Participants With a TEAE of Peripheral Neuropathy Primary · 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)

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

Neuropathy Peripheral
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^20
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^21
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^21
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^21
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^20
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^23
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^23
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^21
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20
Peripheral Sensory Neuropathy
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^20
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^20
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^20
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^21
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^20
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^20
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^20
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^20
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20
Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs Primary · 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)

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.

GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^20
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^20
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^20
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^20
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^21
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^20
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^20
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20
Maximum Tolerated Dose (MTD) of Ixazomib Primary · Cycle 1 (21 days)

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 neu

GroupValue95% CI
Ixazomib (All Groups)2
Recommended Phase 2 Dose (RP2D) of Ixazomib Primary · Cycle 1 through Cycle 39 (Up to 28.3 months)

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.

GroupValue95% CI
Ixazomib (All Groups)2
Cmax: Maximum Observed Plasma Concentration for Ixazomib Secondary · Cycle 1, Days 1 and 11: Predose and at multiple time points (up to 264 hours) postdose
Day 1
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^22.120± 0.3974
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^210.190± 2.5597
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^222.200± 11.3137
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^229.000± 24.1831
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^221.100± 10.1237
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^268.167± 34.7876
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2117.933± 67.1924
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^258.900± 36.1337
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^259.343± 41.9853
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^285.600± 58.8496
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^226.600± NA
Day 11
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^22.837± 1.5051
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^28.857± 5.5598
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^231.650± 15.2028
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^256.500± 14.1421
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2101.100± 71.3597
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^285.420± 30.7632
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2105.450± 41.7900
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^259.871± 32.5851
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^261.800± 24.8780
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2109.660± 27.5668
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^227.200± NA
Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib Secondary · Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
Day 1
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^21.0000.57 – 2.00
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^21.0000.50 – 1.50
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^20.7750.55 – 1.00
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20.7750.50 – 1.05
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^21.0001.00 – 2.02
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^21.0000.25 – 1.08
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^21.0000.72 – 1.08
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^21.0000.52 – 2.00
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^20.6170.50 – 3.97
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20.5250.25 – 1.05
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^21.0001.00 – 1.00
Day 11
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^21.1001.05 – 4.07
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^21.0000.50 – 1.17
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^21.2750.55 – 2.00
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20.5000.50 – 0.50
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^21.0000.57 – 1.05
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^20.6670.50 – 1.50
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^20.8320.53 – 1.13
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^21.0100.50 – 23.60
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^20.5830.50 – 1.03
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^21.5000.62 – 1.53
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^21.5001.5 – 1.5
AUC(0-last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib Secondary · Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 264 hours) postdose
Day 1
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^23.383± 1.7210
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^220.700± 4.5255
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2109.000± 41.0122
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2159.050± 91.8532
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2251.000± 62.5060
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2449.000± 185.9516
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2416.500± 47.3762
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2418.175± 218.7115
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2351.000± 141.4337
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2410.000± 138.7732
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2509.000± NA
Day 11
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^256.533± 15.5095
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2177.667± 115.6820
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2458.000± 42.4264
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2605.000± NA
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2808.500± 212.8391
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^21435.600± 1027.3881
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^21915.000± 148.4924
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2903.846± 382.9033
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2937.857± 334.2082
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^22297.200± 1137.8221
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^21010.000± NA
AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib Secondary · Cycle 1, Days 1 and 11: Predose and at multiple time points (Up to 72 hours) postdose
Day 1
GroupValue95% CI
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2109.00± 41.012
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2159.05± 91.853
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2251.00± 62.506
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2449.00± 185.952
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2416.50± 47.376
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2451.64± 194.522
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2351.00± 141.434
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2410.00± 138.773
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2509.00± NA
Day 11
GroupValue95% CI
Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^256.53± 15.509
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2177.67± 115.682
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2458.00± 42.426
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2605.00± NA
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2808.50± 212.839
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^21435.60± 1027.388
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^21915.00± 148.492
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2903.85± 382.903
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2937.86± 334.208
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^22297.20± 1137.822
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^21010.00± NA
λz: Terminal Disposition Phase Rate Constant for Ixazomib Secondary · Cycle 1, Day 11: predose and at multiple time points (Up to 264 hours) postdose
GroupValue95% CI
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^20.005± NA
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^20.005± 0.0001
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^20.006± 0.0012
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^20.007± 0.0012
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^20.008± 0.0007
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^20.006± 0.0015
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^20.006± 0.0018
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^20.006± 0.0020
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^20.005± NA
T1/2: Terminal Disposition Phase Elimination Half-life for Ixazomib Secondary · Cycle 1, Day 11: predose and at multiple time points (up to 264 hours) postdose
GroupValue95% CI
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2135.00± NA
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2126.50± 2.121
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2129.33± 25.658
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2105.88± 21.071
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^292.70± 8.485
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2115.85± 26.368
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2123.06± 33.877
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2124.93± 41.330
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2134.00± NA

Adverse events — posted to ClinicalTrials.gov

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). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Dose Escalation Cohort 1: Ixazomib 0.24 mg/m^2
Serious: 0/3 (0%)
Deaths: 0/3
Dose Escalation Cohort 2: Ixazomib 0.48 mg/m^2
Serious: 0/3 (0%)
Deaths: 0/3
Dose Escalation Cohort 3: Ixazomib 0.8 mg/m^2
Serious: 2/3 (67%)
Deaths: 1/3
Dose Escalation Cohort 4: Ixazomib 1.2 mg/m^2
Serious: 2/3 (67%)
Deaths: 0/3
Dose Escalation Cohort 5: Ixazomib 1.68 mg/m^2
Serious: 0/3 (0%)
Deaths: 0/3
Dose Escalation Cohort 6: Ixazomib 2.0 mg/m^2
Serious: 5/7 (71%)
Deaths: 0/7
Dose Escalation Cohort 7: Ixazomib 2.23 mg/m^2
Serious: 3/4 (75%)
Deaths: 0/4
Relapsed and Refractory Expansion Cohort: Ixazomib 2.0 mg/m^2
Serious: 14/20 (70%)
Deaths: 1/20
Velcade-Relapsed (VR) Expansion Cohort: Ixazomib 2.0 mg/m^2
Serious: 6/12 (50%)
Deaths: 0/12
Proteasome Inhibitor-Naive Expansion Cohort: Ixazomib 2 mg/m^2
Serious: 3/6 (50%)
Deaths: 0/6
Carfilzomib Expansion Cohort: Ixazomib 2.0 mg/m^2
Serious: 2/2 (100%)
Deaths: 0/2

Serious adverse events (52 terms)

ReactionSystemDose Escalation Cohort 1: …Dose Escalation Cohort 2: …Dose Escalation Cohort 3: …Dose Escalation Cohort 4: …Dose Escalation Cohort 5: …Dose Escalation Cohort 6: …Dose Escalation Cohort 7: …Relapsed and Refractory Ex…Velcade-Relapsed (VR) Expa…Proteasome Inhibitor-Naive…Carfilzomib Expansion Coho…
ThrombocytopeniaBlood and lymphatic system disorders
PyrexiaGeneral disorders
PneumoniaInfections and infestations
DehydrationMetabolism and nutrition disorders
Bone painMusculoskeletal and connective tissue disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
AnaemiaBlood and lymphatic system disorders
Hyperviscosity syndromeBlood and lymphatic system disorders
Febrile neutropeniaBlood and lymphatic system disorders
BacteraemiaInfections and infestations
SepsisInfections and infestations
Septic shockInfections and infestations
Staphylococcal skin infectionInfections and infestations
Urinary tract infectionInfections and infestations
HypercalcaemiaMetabolism and nutrition disorders
HyperuricaemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
Fluid overloadMetabolism and nutrition disorders
Chest painGeneral disorders
Non-cardiac chest painGeneral disorders
ChillsGeneral disorders
Abdominal painGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
GastritisGastrointestinal disorders
NauseaGastrointestinal disorders
Other adverse events (246 terms — click to expand)

ReactionSystemDose Escalation Cohort 1: …Dose Escalation Cohort 2: …Dose Escalation Cohort 3: …Dose Escalation Cohort 4: …Dose Escalation Cohort 5: …Dose Escalation Cohort 6: …Dose Escalation Cohort 7: …Relapsed and Refractory Ex…Velcade-Relapsed (VR) Expa…Proteasome Inhibitor-Naive…Carfilzomib Expansion Coho…
FatigueGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
CoughRespiratory, thoracic and mediastinal disorders
NauseaGastrointestinal disorders
Decreased appetiteMetabolism and nutrition disorders
Upper respiratory tract infectionInfections and infestations
PyrexiaGeneral disorders
DiarrhoeaGastrointestinal disorders
NeutropeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
AstheniaGeneral disorders
Rash macularSkin and subcutaneous tissue disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
ConstipationGastrointestinal disorders
ArthralgiaMusculoskeletal and connective tissue disorders
AnaemiaBlood and lymphatic system disorders
HeadacheNervous system disorders
RashSkin and subcutaneous tissue disorders
Rash pruriticSkin and subcutaneous tissue disorders
Oropharyngeal painRespiratory, thoracic and mediastinal disorders
Dyspnoea exertionalRespiratory, thoracic and mediastinal disorders
Muscle spasmsMusculoskeletal and connective tissue disorders
HyponatraemiaMetabolism and nutrition disorders
Neuropathy peripheralNervous system disorders
ChillsGeneral disorders
PneumoniaInfections and infestations
Back painMusculoskeletal and connective tissue disorders
DehydrationMetabolism and nutrition disorders
DizzinessNervous system disorders
ErythemaSkin and subcutaneous tissue disorders
HyperhidrosisSkin and subcutaneous tissue disorders
PruritusSkin and subcutaneous tissue disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Rash papularSkin and subcutaneous tissue disorders
Skin exfoliationSkin and subcutaneous tissue disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
DysphoniaRespiratory, thoracic and mediastinal disorders
Abdominal discomfortGastrointestinal disorders
PharyngitisInfections and infestations
FuruncleInfections and infestations

Most-reported serious reactions: Thrombocytopenia, Pyrexia, Pneumonia, Dehydration, Bone pain, Hypoxia, Anaemia, Hyperviscosity syndrome.

Data from ClinicalTrials.gov NCT00932698 adverse events section.

Sponsor's own description

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.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.

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Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT00932698.

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