Phase 1
Completed N=32
Study Evaluating the Safety and Tolerability of Weekly Dosing of Oral IXAZOMIB in Adult Patients With Relapsed and Refractory Multiple Myeloma
Source: ClinicalTrials.gov NCT00963820 ↗Enrolled (actual)
32
Serious AEs
34.9%
Results posted
Aug 2015
Primary outcomePrimary: Number of Participants Reporting One or More Treatment-Emergent Adverse Events and Serious Adverse Events — 3; 3; 2; 3 participants
Summary
The primary objective of this study is to determine the safety profile, tolerability, and maximum tolerated dose of ixazomib citrate (MLN9708) when taken orally on a weekly dosing schedule by patients with relapsed and refractory multiple myeloma (RRMM). Secondary objectives include pharmacokinetics and response rates.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Reporting One or More Treatment-Emergent Adverse Events and Serious Adverse Events |
3; 3; 2; 3; 4; 3 | — |
| PRIMARY Neurotoxicity Grading |
36.00; 40.33; 42.00; 36.00; 39.50; 36.80 | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration for MLN2238 |
3.010; 2.91; 5.75; 15.10; 13.83; 29.05 | — |
| SECONDARY Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for MLN2238 |
1.50; 1.53; 1.52; 1.00; 1.52; 1.25 | — |
| SECONDARY AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for MLN2238 |
NA; NA; NA; NA; 258.00; 598.00 | — |
| SECONDARY Accumulation Ratio: Day 15 AUC0-168 / Day 1 AUC0-168 for MLN2238 |
2.64; 1.45; 2.25; 1.19; 2.25; 2.19 | — |
| SECONDARY Terminal Elimination Rate Constant (λz) for MLN2238 |
0.000; 0.000; 0.000; 0.00; 0.00; 0.00 | — |
| SECONDARY Terminal Phase Elimination Half-life (T1/2) for MLN2238 |
271.00; 190.50; 189.00; 175.00; 246.00; 165.00 | — |
| SECONDARY Emax: Maximum Inhibition |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY TEmax: Time of Occurrence of Emax |
NA; NA; NA; NA; NA; NA | — |
| SECONDARY Overall Response to Treatment With Ixazomib Citrate Based on Investigator's Evaluation Over Time |
0; 0; 0; 0; 0; 0 | — |
Eligibility Criteria
Inclusion Criteria
Each patient must meet all of the following eligibility criteria to be enrolled in the study:
- Adult patients with multiple myeloma who have relapsed following at least 2 lines of therapy.
- Patients must have measurable disease.
- Appropriate functional status, including the recovery from the effects of prior antineoplastic therapy, and acceptable organ function as described in the protocol.
- Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or abstain from heterosexual intercourse.
- Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse.
- Willing and able to give written informed consent.
- Suitable venous access for study-required blood sampling.
Exclusion Criteria
- Peripheral neuropathy that is greater or equal to Grade 2.
- Major surgery or, serious infections, or infections that required systemic antibiotic therapy within 14 days before the first dose of study drug.
- Life-threatening illness unrelated to cancer.
- Diarrhea that is greater than Grade 1 as outlined in the protocol
- Systemic antineoplastic or radiation therapy within 14 days or cytotoxic agents, or 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 medications that are outlined in the protocol within 14 days of study treatment.
- Ongoing therapy with corticosteroids greater than 10mg of prednisone or its equivalent per day.
- 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.
- Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection.
- 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 (NCT00963820). 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.