Study Stopped
Sponsor's decision
Study of Dexamethasone Plus IXAZOMIB (MLN9708) or Physicians Choice of Treatment in Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis
A Phase 3, Randomized, Controlled, Open-label, Multicenter, Safety and Efficacy Study of Dexamethasone Plus MLN9708 or Physicians Choice of Treatment Administered to Patients With Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis
7 other identifiers
interventional
177
15 countries
66
Brief Summary
The purpose of this study is to provide continued access of ixazomib and/or other study medications and to continue collecting relevant safety data to monitor participant's safety, determine whether dexamethasone plus IXAZOMIB improves hematologic response, 2-year vital organ (that is, heart or kidney) deterioration and mortality rate versus a physician's choice of a chemotherapy regimen in participants diagnosed with relapsed or refractory systemic light chain (AL) amyloidosis.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3
Started Dec 2012
Longer than P75 for phase_3
66 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 2, 2012
CompletedFirst Posted
Study publicly available on registry
August 8, 2012
CompletedStudy Start
First participant enrolled
December 26, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 11, 2022
CompletedStudy Completion
Last participant's last visit for all outcomes
July 11, 2022
CompletedResults Posted
Study results publicly available
September 21, 2023
CompletedSeptember 2, 2025
August 1, 2025
9.5 years
August 2, 2012
July 10, 2023
August 28, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Participants With Overall Hematologic Response
Overall hematologic response was defined as the percentage of participants with complete response (CR), very good partial response (VGPR) and partial response (PR) based on central laboratory results and the 2010 International Society of Amyloidosis (ISA) Consensus Criteria as assessed by an adjudication committee. CR: Complete disappearance of M-protein from serum and urine on immunofixation, and normalization of free light chain (FLC) ratio. VGPR: differential free light chain (difference between involved and uninvolved FLC levels; dFLC) \< 40 mg/L. PR: ≥50% reduction in dFLC. Percentages were rounded off to the nearest decimal.
From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
2-Year Vital Organ (Heart or Kidney) Deterioration and Mortality Rate
Cardiac (Heart) deterioration was defined as the need for hospitalization for heart failure. Kidney deterioration was defined as progression to end-stage renal disease (ESRD) with the need for maintenance dialysis or renal transplantation. Vital organ deterioration was evaluated by an adjudication committee. Percentages were rounded off to the nearest decimal. As prespecified in the protocol, data was planned to be collected and analyzed in a combined way for non-ixazomib arm groups in this outcome measure.
Up to 2 years
Secondary Outcomes (19)
Percentage of Participants With Complete Hematologic Response
From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
Overall Survival
From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
Progression Free Survival (PFS)
From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
Hematologic Disease Progression Free Survival
From first dose of study drug until discontinuation of study drug due to disease progression or unacceptable toxicity, or death whichever occurs first (up to 115 months)
Time to Vital Organ (Heart or Kidney) Deterioration and Mortality Rate
From randomization to time of vital organ deterioration or death (up to 115 months)
- +14 more secondary outcomes
Study Arms (5)
Arm A: Ixazomib + Dexamethasone
EXPERIMENTALIxazomib 4 mg, capsules, orally, once on Days 1, 8, and 15 and dexamethasone 20 mg, orally, once weekly on Days 1, 8, 15, and 22 of each 28-day cycle for up to a maximum of 95.2 months. Dexamethasone was increased up to 40 mg/day after 4 weeks, if tolerated.
Arm B: Dexamethasone + Melphalan
ACTIVE COMPARATORParticipants received dexamethasone 20 mg, orally, and melphalan 0.22 mg/kg, orally once on Days 1 through 4 of each 28-day cycle, for up to a maximum of 72.4 months.
Arm B: Dexamethasone + Cyclophosphamide
ACTIVE COMPARATORParticipants received dexamethasone 20 mg, orally, once weekly on Days 1, 8, 15, and 22, and cyclophosphamide 500 mg, orally, on Days 1, 8 and 15 of each 28-day cycle for up to a maximum of 72.4 months.
Arm B: Dexamethasone + Thalidomide
ACTIVE COMPARATORParticipants received dexamethasone 20 mg, orally, once weekly on Days 1, 8, 15 and 22 of each 28-day cycle, and thalidomide daily at a starting dose of 50 mg and increased, as tolerated, to a maximum of 200 mg, orally for up to a maximum of 72.4 months.
Arm B: Dexamethasone + Lenalidomide
ACTIVE COMPARATORParticipants received dexamethasone 20 mg, orally, once weekly on Days 1, 8, 15 and 22 of each 28-day cycle and lenalidomide 15 mg, orally, once on Days 1 through 21 every 28 days for up to a maximum of 72.4 months.
Interventions
Dexamethasone tablets
Eligibility Criteria
You may qualify if:
- Male or female participants 18 years or older.
- Biopsy-proven diagnosis of primary systemic light chain amyloidosis (AL amyloidosis) according to the following standard criteria:
- Histochemical diagnosis of amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence
- If clinical and laboratory parameters insufficient to establish AL amyloidosis or in cases of doubt, amyloid typing may be necessary.
- Measurable disease as defined by serum differential free light chain concentration (dFLC, difference between amyloid forming \[involved\] and nonamyloid forming \[uninvolved\] free light chain \[FLC\]) ≥ 50 mg/L.
- Objective, measurable major (cardiac or renal) organ amyloid involvement as defined as follows (amyloid involvement of at least 1 required):
- Cardiac involvement is defined as the presence of a mean left ventricular wall thickness on echocardiogram greater than 12 mm in the absence of other potential causes of left ventricular hypertrophy (controlled hypertension is allowed) with a noncardiac biopsy showing amyloid, or a positive cardiac biopsy in the presence of clinical or laboratory evidence of involvement. If there is isolated cardiac involvement, then typing of amyloid deposits is recommended.
- Renal involvement is defined as proteinuria (predominantly albumin) \>0.5 g/day in a 24-hour urine collection.
- Note: Amyloid involvement of other organ systems is allowed, but not required.
- Must be relapsed or refractory after 1 or 2 prior therapies. For this protocol, relapsed is defined as progressive disease (PD) documented more than 60 days after last dose; refractory is defined as documented absence of hematologic response or hematologic progression on or within 60 days after last dose of prior therapy.
- Participant must not have been previously treated with proteasome inhibitors. (The sponsor reserves the right to open the study to proteasome inhibitor-exposed participants in the future, at some time point after the first interim analysis (IA). In that case, the participant may not be refractory to proteasome inhibitor therapy.)
- Given that the physician may select from an offered list of regimens to treat a specific participant, the participant may be refractory to an agent/s listed within the list of offered treatment choices
- Must have recovered (ie, ≤ Grade 1 toxicity or participant's baseline status) from the reversible effects of prior therapy
- If a participant has received a transplant as his/her first-line therapy, he/she must be at least 3 months post transplantation and recovered from the side effects of the stem cell transplant.
- Must meet criteria for 1 of the following AL Amyloidosis Risk Stages (as defined by N-terminal proBNP \[NT-proBNP\] cut-off of \< 332 pg/mL and troponin T cut-off of 0.035 ng/mL as thresholds):
- +20 more criteria
You may not qualify if:
- Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis.
- Female participants who are lactating, breast feeding, or pregnant.
- Medically documented cardiac syncope, uncompensated New York Heart Association (NYHA) Class 3 or 4 congestive heart failure, myocardial infarction within the previous 6 months, unstable angina pectoris, clinically significant repetitive ventricular arrhythmias despite antiarrhythmic treatment, or severe orthostatic hypotension or clinically important autonomic disease.
- Clinically overt multiple myeloma, according to the International Myeloma Working Group (IMWG) criteria with at least 1 of the following:
- Bone lesions
- Hypercalcemia, defined as a calcium of \> 11 mg/dL
- Inability to swallow oral medication, inability or unwillingness to comply with the drug administration requirements, or gastrointestinal (GI) procedure that could interfere with the oral absorption or tolerance of treatment.
- Requirement for other concomitant chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered to be investigational or which would be considered as a treatment of AL amyloidosis. However, participants may be on chronic steroids (maximum dose 20 mg/day prednisone or equivalent) if they are being given for disorders other than amyloidosis (eg, adrenal insufficiency, rheumatoid arthritis, etc.).
- Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
- Ongoing or active infection, known human immunodeficiency virus (HIV) positive, active hepatitis B or C infection.
- Psychiatric illness/social situations that would limit compliance with study requirements.
- Known allergy to boron, MLN9708, any of the study treatments, their analogues, or excipients.
- Systemic treatment with strong CYP3A inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital), or use of Ginkgo biloba or St. John's wort within 14 days before the first dose of study treatment.
- Diagnosed or treated for another malignancy within 3 years (or 5 years for participants in France) before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (66)
Cedars Sinai Medical Center
Los Angeles, California, 90048, United States
University of Chicago
Chicago, Illinois, 60637, United States
Indiana University School of Medicine
Indianapolis, Indiana, 46202, United States
Tufts Medical Center
Boston, Massachusetts, 00211, United States
Boston Medical Center
Boston, Massachusetts, 02118, United States
Karmanos Cancer Institute
Detroit, Michigan, 48201, United States
Mayo Clinic
Rochester, Minnesota, 05590, United States
Washington University
St Louis, Missouri, 63110, United States
Columbia University Medical Center
New York, New York, 10032, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
University of Cincinnati
Cincinnati, Ohio, 45267, United States
Cleveland Clinic
Cleveland, Ohio, 44195, United States
Vanderbilt University Medical Center
Nashville, Tennessee, 37232, United States
University of Texas Southwestern Medical Center
Dallas, Texas, 75390, United States
Froedtert and The Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Westmead Hospital
Westmead, New South Wales, 214, Australia
Princess Alexandra Hospital
Woolloongabba, Queensland, 4102, Australia
Box Hill Hospital
Box Hill, Victoria, 3128, Australia
Sir Charles Gairdner Hospital
Nedlands, Western Australia, 6009, Australia
Centro de Pesquisas Oncologicas
FlorianĂ³polis, Santa Catarina, 88034-000, Brazil
Hospital Universitario Clementino Fraga Filho (UFRJ)
Rio de Janeiro, 21941-913, Brazil
Irmandade Da Santa Casa de Misericordia de Sao Paulo
SĂ£o Paulo, 01223-001, Brazil
Hospital Israelita Albert Einstein
SĂ£o Paulo, 05652-900, Brazil
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
SĂ£o Paulo, 5403000, Brazil
Tom Baker Cancer Centre
Calgary, Alberta, T2N 4N2, Canada
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z, Canada
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M, Canada
Princess Margaret Hospital
Toronto, Ontario, M5G2M9, Canada
Fakultni nemocnice Ostrava
Ostrava, Moravskoslezsk Kraj, 708 52, Czechia
Vseobecna fakultni nemocnice v Praze
Prague, Praha, Hlavni Mesto, 128 08, Czechia
Arhus Universitetshospital Arhus Sygehus
Aahus, 800, Denmark
Rigshospitalet
Copenhagen, 2100, Denmark
Hotel Dieu
Nantes, Loire-Atlantique, 44093, France
Hopital Claude Huriez
Lille, 5903, France
Centre Hospitalier et Universitaire de Limoges
Limoges, 87042, France
Hopital Saint Louis
Paris, 75010, France
Hopital de Rangueil
Toulouse, 31059, France
Charite - Universitatsmedizin Berlin
Berlin, 12200, Germany
Universitatsklinikum Hamburg Eppendorf
Hamburg, 20246, Germany
Universitat Heidelberg
Heidelberg, 69120, Germany
University General Hospital of Patras
PĂ¡trai, Achaia, 26500, Greece
Alexandra Hospital
Athens, 11528, Greece
Rambam Health Corporation
Haifa, 31096, Israel
Hadasit Medical Research Services and Development Ltd
Jerusalem, 911, Israel
Meir Medical Center
Kfar Saba, 44281, Israel
Rabin Medical Center - PPDS
Petah Tikva, 49100, Israel
Chaim Sheba Medical Center
Ramat Gan, 52621, Israel
Institute of Hematology "Seragnoli" University of Bologna
Bologna, 40138, Italy
Fondazione IRCCS Policlinico San Matteo di Pavia
Pavia, 2710, Italy
VU Medisch Centrum
Amsterdam, North Holland, 1081 HV, Netherlands
Maastricht University Medical Center
AZ Maastricht, 620, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht, 3508, Netherlands
Gachon University Gil Medical Center
Incheon, 405-760, South Korea
Seoul National University Hospital
Seoul, 110744, South Korea
Severance Hospital at Yonsei University Health System - PPDS
Seoul, 120-752, South Korea
Samsung Medical Center - PPDS
Seoul, 135-710, South Korea
The Catholic University of Korea, Seoul St Mary's Hospital
Seoul, 137-70, South Korea
Clinica Universidad de Navarra
Pamplona, Navarre, 31008, Spain
Hospital Clinic de Barcelona
Barcelona, 8036, Spain
Hospital Universitario de La Princesa
Madrid, 28006, Spain
Hospital Universitario Puerta de Hierro - Majadahonda
Majadahonda, 28222, Spain
Hospital Universitario de Salamanca
Salamanca, 37007, Spain
Queen Elizabeth Hospital
Birmingham, B152TH, United Kingdom
Royal Free and University College Medical School
London, NW3 2P, United Kingdom
Manchester Royal Infirmary
Manchester, MI3 9WL, United Kingdom
Oxford University Hospitals NHS Trust
Oxford, OX3 7L, United Kingdom
Related Publications (2)
Sanchorawala V, Wechalekar AD, Kim K, Schonland SO, Landau HJ, Kwok F, Suzuki K, Dispenzieri A, Merlini G, Comenzo RL, Cherepanov D, Hayden VC, Kumar A, Labotka R, Faller DV, Kastritis E. Quality of life and symptoms among patients with relapsed/refractory AL amyloidosis treated with ixazomib-dexamethasone versus physician's choice. Am J Hematol. 2023 May;98(5):720-729. doi: 10.1002/ajh.26866. Epub 2023 Feb 14.
PMID: 36708469DERIVEDSanchorawala V, Palladini G, Kukreti V, Zonder JA, Cohen AD, Seldin DC, Dispenzieri A, Jaccard A, Schonland SO, Berg D, Yang H, Gupta N, Hui AM, Comenzo RL, Merlini G. A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis. Blood. 2017 Aug 3;130(5):597-605. doi: 10.1182/blood-2017-03-771220. Epub 2017 May 26.
PMID: 28550039DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Study Director
- Organization
- Takeda
Study Officials
- STUDY DIRECTOR
Medical Director
Takeda
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 2, 2012
First Posted
August 8, 2012
Study Start
December 26, 2012
Primary Completion
July 11, 2022
Study Completion
July 11, 2022
Last Updated
September 2, 2025
Results First Posted
September 21, 2023
Record last verified: 2025-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Access Criteria
- IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.