Phase 2
Completed N=61
Study of Oral Ixazomib in Combination With Melphalan and Prednisone in Participants With Newly Diagnosed Multiple Myeloma
Source: ClinicalTrials.gov NCT01335685 ↗Enrolled (actual)
61
Serious AEs
50.8%
Results posted
Jan 2018
Primary outcomePrimary: Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Ixazomib (Phase 1) — 3; 4; 3; 4 mg
Summary
The purpose of this phase 1/2, open-label study was to evaluate the effect of oral formulation of Ixazomib when added to standard melphalan and prednisone (MP) treatment. Both phases of the study included participants who had newly diagnosed multiple myeloma and were ineligible for high-dose therapy plus stem cell transplantation because of age (≥65 years of age) or coexisting conditions and for whom standard MP treatment was indicated.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Ixazomib (Phase 1) |
3; 4; 3; 4 | — |
| PRIMARY Very Good Partial Response (VGPR) or Better Response Rate (Phase 2) |
48 | — |
| SECONDARY Maximum Inhibition Rate (Emax) (Phase 1) |
— | — |
| SECONDARY Time of Occurrence of Emax (TEmax) (Phase 1) |
— | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration for Ixazomib (Phase 1) |
26.791; 39.300; 22.950; 53.278; 104.225; 55.367 | — |
| SECONDARY Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib (Phase 1) |
1.020; 0.517; 1.750; 1.000; 1.302; 1.560 | — |
| SECONDARY AUCtau: Area Under the Plasma Concentration-time Curve Over the Dosing Interval for Ixazomib (Phase 1) |
319.714; 287.000; 450.000; 806.824; 1612.250; 662.833 | — |
| SECONDARY Terminal Elimination Rate Constant (λz) for Ixazomib (Phase 1) |
0.004; 0.006; 0.007; NA; 0.005; 0.005 | — |
| SECONDARY Terminal Phase Elimination Half-life (T1/2) for Ixazomib (Phase 1) |
167.000; 130.362; 98.900; NA; 140.575; 163.500 | — |
| SECONDARY Observed Accumulation Ratio for AUCtau (Rac) (Phase 1) |
4.019; 4.120; 1.700; 2.288; 1.970; 2.632 | — |
| SECONDARY Overall Response Rate (ORR) |
86; 67; 100; 65; 60; 40 | — |
| SECONDARY Time to First Response (Phase 2) |
1.9 | — |
| SECONDARY Duration of Response (DOR) (Phase 2) |
25.2 | — |
| SECONDARY Time to Progression (TTP) (Phase 2) |
22.1 | — |
| SECONDARY Time to Next Therapy (Phase 2) |
— | — |
| SECONDARY Progression Free Survival (Phase 2) |
18.4 | — |
| SECONDARY Overall Survival (Phase 2) |
NA | — |
| SECONDARY Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) |
7; 4; 3; 26; 5; 6 | — |
| SECONDARY Assessments of Quality of Life (Phase 2) |
— | — |
Eligibility Criteria
Inclusion Criteria
- Is indicated with standard melphalan prednisone (MP) treatment and is not a candidate for high-dose therapy plus stem cell transplantation (HDT-SCT) for 1 of the following reasons: the participant is 65 years of age or older OR the participant is less than 65 years of age but has significant comorbid condition(s) that are likely to have a negative impact on tolerability of HDT-SCT
- Is diagnosed with symptomatic multiple myeloma or asymptomatic myeloma with myeloma-related organ damage according to standard criteria
- Has measurable disease as specified in study protocol
- Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Has adequate hematologic, liver, and renal function
Exclusion Criteria
- Has peripheral neuropathy that is greater or equal to Grade 2
- Has major surgery or radiotherapy within 14 days before the first dose of study drug
- Has uncontrolled infection requiring systematic antibiotics
- Has diarrhea (> Grade 1)
- Has prior systemic therapy for multiple myeloma, including investigational drugs (prior treatment with corticosteroids or localized radiation therapy dose not disqualify the participantt)
- Has central nervous system involvement
- Has cardiac status as described in protocol
- Has known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of IXAZOMIB - Diagnosis of smoldering multiple myeloma, Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome
- Has Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
- Is diagnosed or treated for another malignancy within 2 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease with the exception of nonmelanoma skin cancer or any completely resected carcinoma in situ
- Has serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol
Data sourced from ClinicalTrials.gov (NCT01335685). 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.