Phase 1
N=27
Study of Oral Ixazomib in Adult Participants With Relapsed or Refractory Light Chain Amyloidosis
Light-Chain Amyloidosis
Bottom Line
View on ClinicalTrials.gov: NCT01318902 ↗Enrolled (actual)
27
Serious AEs
66.7%
Results posted
Apr 2020
Primary outcome: Primary: Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) — 6; 5; 5; 10 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- Ixazomib (Drug); Dexamethasone (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Millennium Pharmaceuticals, Inc.
- Primary completion
- Nov 2018
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With at Least One Treatment Emergent Adverse Event (TEAE) and Serious Adverse Event (SAE) |
6; 5; 5; 10; 3; 5 | — |
| PRIMARY Number of Participants With Clinically Significant Abnormal Laboratory Values Reported as TEAE |
2; 0; 2; 2; 2; 0 | — |
| PRIMARY Number of Participants With Peripheral Neuropathy Reported as a TEAE |
1; 0; 1; 1; 1; 0 | — |
| PRIMARY Maximum Tolerated Dose (MTD) of Ixazomib |
4; 4 | — |
| PRIMARY Recommended Phase 2 Dose (RP2D) of Ixazomib |
4; 4 | — |
| SECONDARY Cmax: Maximum Observed Plasma Concentration for Ixazomib |
54.00; 51.26; 92.20 | — |
| SECONDARY Tmax: Time of First Occurrence of Cmax for Ixazomib |
1.0000; 1.0000; 0.7500 | — |
| SECONDARY Ctrough: Plasma Concentration Immediately Prior to Dosing for Ixazomib |
2.1539; 2.9140; 5.3300 | — |
| SECONDARY AUC0-168: Area Under the Plasma Concentration-time Curve From Time 0 to 168 Hours Post-dose for Ixazomib |
861.0; 1078.1; 1725.0 | — |
| SECONDARY Emax: Maximum Observed Percent Inhibition of Whole Blood 20S Proteasome |
54.10; 61.09 | — |
| SECONDARY TEmax: Time to Maximum Observed Effect (Emax) of Whole Blood 20S Proteasome Inhibition for Ixazomib |
1.0000; 1.0300 | — |
| SECONDARY AUE0-168: Area Under Effect Curve of Whole Blood 20S Proteasome Inhibition From Zero to Concentration at 168 Hours for Ixazomib |
3333.6; 3943.0 | — |
| SECONDARY Number of Participants With Best Organ Response to Treatment Based on Investigators Assessment |
2; 0; 2; 2 | — |
| SECONDARY Number of Participants With Best Hematologic Response to Treatment Based on Investigators Assessment |
4; 0; 4; 3 | — |
| SECONDARY Time to First Hematologic Response |
0.79; 3.45; 2.11 | — |
| SECONDARY Time to First Organ Response |
6.85; 9.55; 6.85 | — |
| SECONDARY Duration of Hematologic Response |
12.9; 69.5; 19.7 | — |
| SECONDARY Duration of Organ Response |
4.1; 20.5; 18.25 | — |
| SECONDARY Time to Hematologic Disease Progression |
14.8; NA; 73.0; 8.3 | — |
| SECONDARY Time to Organ Disease Progression |
11; 12.85; 25.15 | — |
| SECONDARY Hematologic Disease Progression-Free Survival (PFS) |
14.8; 7.2; 73.0; 8.3 | — |
| SECONDARY Organ Disease Progression-Free Survival (PFS) |
NA; NA; NA; NA | — |
| SECONDARY Percentage of Participants With One Year Hematologic Disease PFS |
83.3; 80.0; 21.5 | — |
Summary
This study will include participants with previously treated systemic relapsed or refractory light-chain (AL) amyloidosis who require further therapy and will be aimed at determining the safety profile and the maximum tolerated dose/recommended phase 2 dose of MLN9078 (Ixazomib) administered orally.
Eligibility Criteria
Inclusion Criteria
- Male or female participants 18 years or older
- Biopsy-proven systemic relapsed or refractory light-chain (AL) amyloidosis, which after at least 1 prior therapy, in the investigator's opinion, requires further treatment
- If received stem cell transplant, must be at least 3 months posttransplantation and recovered from side effects
- Must have measurable disease defined as serum differential free light chain concentration ≥ 40 mg/L
- Must have objective measurable organ (heart or kidney) amyloid involvement
- Must have cardiac biomarker risk stage I or II disease
- Must have adequate hematologic, hepatic, and renal function
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
- Female participants who are postmenopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse
- Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
- Voluntary written consent
Exclusion Criteria
- Peripheral neuropathy that is greater or equal to Grade 2
- Cardiac status as described in protocol
- Severe diarrhea (≥ Grade 3) not controllable with medication or requires administration of total parenteral nutrition
- Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of MLN9708
- Uncontrolled infection requiring systematic antibiotics
- Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
- Presence of other active malignancy with the exception of nonmelanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate-specific antigen is within normal limit, or any completely resected carcinoma in situ
- Female participants who are lactating or pregnant
- Major surgery within 14 days before the first dose of study drug
- 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 (NCT01318902). 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.