Phase 2
Completed N=64
Study of Oral IXAZOMIB in Combination With Lenalidomide and Dexamethasone in Participants With Newly Diagnosed Multiple Myeloma
Source: ClinicalTrials.gov NCT01383928 ↗Enrolled (actual)
64
Serious AEs
46.9%
Results posted
Dec 2015
Primary outcomePrimary: Phase 1: Maximum Tolerated Dose (MTD) — 3.7 mg
Summary
The purpose of this study is to determine the safety, tolerability, maximum tolerated dose (MTD), and recommended phase 2 dose (RP2D) in phase 1 and to determine the combined response rate of clinical response CR and very good partial response (VGPR) in phase 2 of oral (PO) ixazomib administered twice-weekly in combination with lenalidomide and low-dose dexamethasone in a 21-day cycle in participants with newly diagnosed multiple myeloma (NDDM).
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Phase 1: Maximum Tolerated Dose (MTD) |
3.7 | — |
| PRIMARY Phase 1: Recommended Phase 2 Dose (RP2D) |
3 | — |
| PRIMARY Phase 1: Percentage of Participants Experiencing 1 or More Treatment-Emergent Adverse Events (TEAEs) or Serious Adverse Events (SAEs) |
100; 100; 71; 29 | — |
| PRIMARY Phase 1: Number of Participants With Markedly Abnormal Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs) |
0; 3; 0; 2; 2; 0 | — |
| PRIMARY Phase 1: Number of Participants With Treatment-Emergent Adverse Events (TEAE) Related to Neurotoxicity |
0; 1; 2; 1; 0; 1 | — |
| PRIMARY Phase 1: Number of Participants With Clinically Significant Change From Baseline in Vital Signs |
1; 3; 1; 0; 0; 1 | — |
| PRIMARY Phase 2: Percentage of Participants With Complete Response (CR) + Very Good Partial Response (VGPR) |
65 | — |
| PRIMARY Phase 2: Percentage of Participants With Grade 3 or Higher Adverse Events |
74 | — |
| PRIMARY Phase 2: Percentage of Participants Experiencing Serious Adverse Events |
46 | — |
| PRIMARY Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events Resulting in Study Drug Discontinuation |
14 | — |
| SECONDARY Phase 1: Cmax: Maximum Plasma Concentration for Ixazomib |
33.515; 46.946; 58.674; 51.832 | — |
| SECONDARY Phase 1: AUC(0-72): Area Under the Plasma Concentration-Time Curve From Time 0 to 72 Hours Postdose for Ixazomib |
315.450; 284.576; 1105.44; 1023.52 | — |
| SECONDARY Phase 1: Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Ixazomib |
1.035; 1.000; 1.030; 0.984 | — |
| SECONDARY Phase 1: Rac: Accumulation Ratio of Ixazomib |
3.785; 3.967 | — |
| SECONDARY Phase 1: Percentage of Participants With Best Overall Response |
92 | — |
| SECONDARY Phase 2: Percentage of Participants With Overall Response (CR+VGPR+PR) |
94 | — |
| SECONDARY Phase 2: Percentage of Participants With Complete Response (CR) and Very Good Partial Response (VGPR) After Cycles 4, 8, and 16 |
49; 64; 92 | — |
| SECONDARY Phase 2: Percentage of Participants With Complete Response (CR) |
29 | — |
| SECONDARY Phase 2: Percentage of Participants With Stringent Complete Response (sCR) |
22 | — |
| SECONDARY Phase 2: Percentage of Participants With Very Good Partial Response (VGPR) |
37 | — |
| SECONDARY Phase 2: Percentage of Participants With Near Complete Response (nCR) |
10 | — |
| SECONDARY Phase 2: Percentage of Participants With Partial Response (PR) |
65 | — |
| SECONDARY Phase 2: Percentage of Participants With Minimal Response (MR) |
6 | — |
| SECONDARY Phase 2: Time to Response |
0.72 | — |
| SECONDARY Phase 2: Duration of Response (DOR) |
29.0 | — |
| SECONDARY Time to Disease Progression (TTP) |
29.7 | — |
| SECONDARY Progression Free Survival (PFS) |
29.7 | — |
| SECONDARY Kaplan-Meier Estimate of Percentage of Participants Achieving Survival at Year 1 |
94 | — |
| SECONDARY Overall Survival |
NA | — |
Eligibility Criteria
Inclusion Criteria
- Male or female patients 18 years or older
- Symptomatic multiple myeloma or asymptomatic myeloma with myeloma-related organ damage diagnosed according to standard criteria
- Measurable disease as specified in study protocol
- Hematologic, liver, and renal function as specified in the study protocol.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse; must also adhere to the guidelines of the lenalidomide pregnancy prevention program
- Male patients who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse AND 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
- 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
- Uncontrolled infection requiring systematic antibiotics within 14 days before the first dose of study drug
- Diarrhea (> Grade 1)
- Prior systemic therapy for multiple myeloma, including investigational drugs (prior treatment with corticosteroids or localized radiation therapy dose not disqualify the patient)
- Systemic treatment with strong inhibitors of CYP1A2, strong inhibitors of CYP3A, or strong CYP3A inducers, or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study treatment
- Central nervous system involvement
- Diagnosis of smoldering multiple myeloma, Waldenstrom's macroglobulinemia, POEMS syndrome, plasma cell leukemia, primary amyloidosis, myelodysplastic syndrome, or myeloproliferative syndrome
- Evidence of current uncontrolled cardiovascular conditions
- Prior or concurrent deep vein thrombosis or pulmonary embolism
- 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 allergy to any of the study medications
- Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption, or tolerance of IXAZOMIB
- 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
Data sourced from ClinicalTrials.gov (NCT01383928). 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.