Phase 1
Completed N=26
Study of Oral Ixazomib in Adult Participants With Relapsed and/or Refractory (RR) Multiple Myeloma
Source: ClinicalTrials.gov NCT00932698 ↗Enrolled (actual)
26
Serious AEs
56.1%
Results posted
Aug 2019
Primary outcomePrimary: Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) — 3; 3; 3; 3 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) |
3; 3; 3; 3; 3; 7 | — |
| PRIMARY Number of Participants With Clinically Significant Abnormalities Reported as TEAEs |
1; 1; 1; 0; 0; 1 | — |
| PRIMARY Number of Participants With a TEAE of Peripheral Neuropathy |
0; 1; 1; 0; 0; 1 | — |
| PRIMARY Number of Participants With Clinically Significant Changes in Vital Signs Reported as TEAEs |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Maximum Tolerated Dose (MTD) of Ixazomib |
2 | — |
| PRIMARY Recommended Phase 2 Dose (RP2D) of Ixazomib |
2 | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration for Ixazomib |
2.120; 10.190; 22.200; 29.000; 21.100; 68.167 | — |
| SECONDARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib |
1.000; 1.000; 0.775; 0.775; 1.000; 1.000 | — |
| SECONDARY AUC(0-last): Area Under the Plasma Concentration-Time Curve From Time 0 to the Time of the Last Quantifiable Concentration for Ixazomib |
3.383; 20.700; 109.000; 159.050; 251.000; 449.000 | — |
| SECONDARY AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib |
109.00; 159.05; 251.00; 449.00; 416.50; 451.64 | — |
| SECONDARY λz: Terminal Disposition Phase Rate Constant for Ixazomib |
0.005; 0.005; 0.006; 0.007; 0.008; 0.006 | — |
| SECONDARY T1/2: Terminal Disposition Phase Elimination Half-life for Ixazomib |
135.00; 126.50; 129.33; 105.88; 92.70; 115.85 | — |
| SECONDARY CL/F: Blood Clearance Calculated Using the Observed Value of the Last Quantifiable Concentration for Ixazomib |
— | — |
| SECONDARY Emax: Maximum Observed Effect for Ixazomib |
— | — |
| SECONDARY TEmax: Time to Maximum Observed Effect (Emax) for Ixazomib |
— | — |
| SECONDARY Overall Response Rate (ORR) |
0; 0; 0; 33; 0; 0 | — |
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.
Data sourced from ClinicalTrials.gov (NCT00932698). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.