Phase 2
Completed N=15
A Study of Ixazomib Administered in Combination With Lenalidomide and Low-Dose Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma
Source: ClinicalTrials.gov NCT01217957 ↗Enrolled (actual)
15
Serious AEs
43.1%
Results posted
Jan 2016
Primary outcomePrimary: Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability — 3; 3; 6; 3 participants
Summary
The purpose of Phase 1 of this study was to determine the safety, tolerability, maximum tolerated dose (MTD), and recommended Phase 2 dose (RP2D) of oral ixazomib administered in combination with lenalidomide and low-dose dexamethasone in participants with newly diagnosed multiple myeloma (NDMM). The purpose of Phase 2 of this study was to determine the overall response rate (ORR) and further evaluate the tolerability and toxicity of the combination of oral ixazomib, lenalidomide, and low-dose dexamethasone in patients with NDMM.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability |
3; 3; 6; 3; 2; 3 | — |
| PRIMARY Phase 2: Objective Response Rate (ORR) Following Treatment With the Combination Of Oral Ixazomib, Lenalidomide And Low-Dose Dexamethasone |
59; 62 | — |
| PRIMARY Phase 1: Recommended Phase 2 Dose of Ixazomib Given in Combination With Lenalidomide and Low-Dose Dexamethasone |
2.23 | — |
| PRIMARY Phase 1: Maximum Tolerated Dose (MTD) of Ixazomib Administered Weekly in Combination With Lenalidomide and Low-Dose Dexamethasone |
2.97 | — |
| PRIMARY Phase 2: Percentage of Participants With Grade 3 or Higher AEs, SAEs and Treatment Discontinuation |
76; 75; 40; 43; 8; 8 | — |
| SECONDARY Phase 1: Cmax: Maximum Observed Plasma Concentration for Ixazomib |
NA; 22.303; 94.779; NA; 11.999; 31.368 | — |
| SECONDARY Phase 1: Tmax: Time to Reach the Maximum Observed Plasma Concentration (Cmax) for Ixazomib |
1.020; 1.520; 1.060; 0.250; 4.165; 1.000 | — |
| SECONDARY Phase 1: AUC(0-168): Area Under the Plasma Concentration-Time Curve From Time 0 to 168 Hours Postdose for Ixazomib |
NA; 587.667; 923.484; NA; 834.608; 1083.998 | — |
| SECONDARY Phase 1: Rac: Accumulation Ratio of Ixazomib |
NA; 1.849; 2.051 | — |
| SECONDARY Phase 1: Emax: Maximum Observed Inhibition of Whole Blood 20S Proteasome |
— | — |
| SECONDARY Phase 1: TEmax: Time to the Maximum Observed Inhibition of Whole Blood 20S Proteasome |
— | — |
| SECONDARY Phase 2: Time to Progression (TTP) |
NA; NA | — |
| SECONDARY Phase 2: Overall Survival (OS) |
NA; NA | — |
| SECONDARY Phase 2: Overall Response Rate (ORR) |
88; 88 | — |
| SECONDARY Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) |
35; 37; 47; 48; 57; 58 | — |
| SECONDARY Phase 2: Percentage of Participants With Complete Response (CR), Stringent Complete Response (sCR), Very Good Partial Response (VGPR), Near Complete Response (nCR), Partial Response (PR) and Minimal Response (MR) |
20; 23; 6; 10; 39; 38 | — |
| SECONDARY Phase 2: Time to Best Response |
2.96; 3.01 | — |
| SECONDARY Phase 2: Duration of Response (DOR) |
NA; NA | — |
| SECONDARY Phase 2: Progression Free Survival (PFS) |
14.98; NA | — |
| SECONDARY Phase 2: 1 Year Survival Rate |
92; 92 | — |
Eligibility Criteria
Inclusion Criteria
Each patient must meet all of the following eligibility criteria to be enrolled in the study:
- Male or female patients 18 years or older
- Previously untreated multiple myeloma diagnosed according to standard criteria requiring systemic treatment
- Patients must have measurable disease
- Nonsecretory multiple myeloma based upon standard M-component criteria (i.e., measurable serum/urine M-component) is not allowed unless the baseline serum free light chain level (Freelite™) is evaluated Patients must meet clinical laboratory criteria as specified in study protocol
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Female and male patients MUST adhere to the guidelines of the lenalidomide pregnancy prevention program
- Must be able to take concurrent aspirin 325 mg daily
- Voluntary written consent
Exclusion Criteria
Patients meeting any of the following exclusion criteria are not to be enrolled in the study:
- Peripheral neuropathy that is greater or equal to Grade 2
- Female patients who are lactating or pregnant
- Major surgery or radiotherapy within 14 days before the first dose of study drug
- Serious infection requiring systemic antibiotic therapy within 14 days before the first dose of study drug
- Diarrhea greater than Grade 1 based on the National Cancer Institute Common Terminology Criteria for Adverse Events
- Central nervous system involvement.
- Evidence of current uncontrolled cardiovascular conditions 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 condition that could interfere with swallowing or the oral absorption or tolerance of ixazomib
- No other prior malignancy within 2 years except nonmelanoma skin cancer or carcinoma in situ of any type if they have undergone complete resection
Data sourced from ClinicalTrials.gov (NCT01217957). 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.