Promising drug combo for rare amyloidosis hits snag: trial ends early

NCT ID NCT01659658

Disease control Sponsor: Millennium Pharmaceuticals, Inc. Source: ClinicalTrials.gov ↗

First seen Jun 26, 2026 · Last updated Jun 26, 2026 · Updated 1 time

Summary

This study tested a drug called ixazomib plus dexamethasone against other standard treatments for people with relapsed AL amyloidosis, a rare disease where abnormal proteins build up in organs. The trial aimed to see if the combination improved blood markers and slowed heart or kidney damage. It enrolled 177 adults but was terminated early, so the full benefits and risks are not yet clear.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: Ixazomib (a cancer drug) plus dexamethasone (a steroid)
What this could lead to: If successful, this could offer a new treatment option for people with relapsed AL amyloidosis, potentially improving blood responses and delaying organ damage.
What could go wrong: The trial was terminated early, so results are limited. It is unclear if ixazomib is better than other treatments, and side effects like nausea, fatigue, and low blood counts are possible.

This is an AI summary of the original study and may miss details. Read our disclaimer.

Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 3

Large-scale testing in a bigger group. Usually the last step before a treatment can be approved.

Participants

177 people

The number who actually took part.

Started

Dec 2012

Finished

Jul 2022

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 years and older

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: 1. Male or female participants 18 years or older. 2. Biopsy-proven diagnosis of primary systemic light chain amyloidosis (AL amyloidosis) according to the following standard criteria: 1. Histochemical diagnosis of amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence 2. If clinical and laboratory parameters insufficient to establish AL amyloidosis or in cases of doubt, amyloid typing may be necessary. 3. 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. 4. Objective, measurable major (cardiac or renal) organ amyloid involvement as defined as follows (amyloid involvement of at least 1 required): 1. 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. 2. 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. 5. 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. 1. 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.) 2. 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 3. Must have recovered (ie, ≤ Grade 1 toxicity or participant's baseline status) from the reversible effects of prior therapy 4. 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. 6. 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): 1. Stage 1: both NT-proBNP and troponin T under threshold 2. Stage 2: either NT-proBNP or troponin T (but not both) over threshold; 3. Stage 3: both NT-proBNP and troponin T over threshold (but NT-proBNP \< 8000 pg/mL) 7. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2. 8. Clinical laboratory values: 1. Absolute neutrophil count ≥ 1000/µL 2. Platelet count ≥ 75,000/µL 3. Total bilirubin ≤ 1.5 upper limit of normal (ULN), except for participants with Gilbert's syndrome as defined by \> 80% unconjugated bilirubin and total bilirubin ≤ 6 mg/dL 4. Alkaline phosphatase ≤ 5 x ULN 5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3 x ULN 6. Calculated creatinine clearance ≥ 30 mL/min 9. Female participants who: 1. If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 90 days after the last dose of study treatment, AND 2. Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR 3. Agree to practice true abstinence when this is line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.). Male participants, even if surgically sterilized (ie, status post vasectomy), who: 1. Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, AND 2. Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR 3. Agree to practice true abstinence when this is line with the preferred and usual lifestyle of the participant. (Periodic abstinence \[eg, calendar, ovulation, symptothermal, post-ovulation methods\] and withdrawal are not acceptable methods of contraception.) 10. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care with the understanding that consent may be withdrawn by the participant at any time without prejudice to future medical care. Exclusion Criteria: 1. Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis. 2. Female participants who are lactating, breast feeding, or pregnant. 3. 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. 4. Clinically overt multiple myeloma, according to the International Myeloma Working Group (IMWG) criteria with at least 1 of the following: 1. Bone lesions 2. Hypercalcemia, defined as a calcium of \> 11 mg/dL 5. 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. 6. 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.). 7. 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. 8. Ongoing or active infection, known human immunodeficiency virus (HIV) positive, active hepatitis B or C infection. 9. Psychiatric illness/social situations that would limit compliance with study requirements. 10. Known allergy to boron, MLN9708, any of the study treatments, their analogues, or excipients. 11. 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. 12. 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.

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Conditions

The condition(s) this trial relates to.

AL amyloidosis amyloidosis Recurrence

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Relapsed or refractory systemic light chain amyloidosis

Contacts and locations

Locations

Alexandra Hospital

Athens, 11528, Greece
Arhus Universitetshospital Arhus Sygehus

Aahus, 800, Denmark
Boston Medical Center

Boston, Massachusetts, 02118, United States
Box Hill Hospital

Box Hill, Victoria, 3128, Australia
Cedars Sinai Medical Center

Los Angeles, California, 90048, United States
Centre Hospitalier et Universitaire de Limoges

Limoges, 87042, France
Centro de Pesquisas Oncologicas

Florianópolis, Santa Catarina, 88034-000, Brazil
Chaim Sheba Medical Center

Ramat Gan, 52621, Israel
Charite - Universitatsmedizin Berlin

Berlin, 12200, Germany
Cleveland Clinic

Cleveland, Ohio, 44195, United States
Clinica Universidad de Navarra

Pamplona, Navarre, 31008, Spain
Columbia University Medical Center

New York, New York, 10032, United States
Cross Cancer Institute

Edmonton, Alberta, T6G 1Z, Canada
Fakultni nemocnice Ostrava

Ostrava, Moravskoslezsk Kraj, 708 52, Czechia
Fondazione IRCCS Policlinico San Matteo di Pavia

Pavia, 2710, Italy
Froedtert and The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States
Gachon University Gil Medical Center

Incheon, 405-760, South Korea
Hadasit Medical Research Services and Development Ltd

Jerusalem, 911, Israel
Hopital Claude Huriez

Lille, 5903, France
Hopital Saint Louis

Paris, 75010, France
Hopital de Rangueil

Toulouse, 31059, France
Hospital Clinic de Barcelona

Barcelona, 8036, Spain
Hospital Israelita Albert Einstein

São Paulo, 05652-900, Brazil
Hospital Universitario Clementino Fraga Filho (UFRJ)

Rio de Janeiro, 21941-913, Brazil
Hospital Universitario Puerta de Hierro - Majadahonda

Majadahonda, 28222, Spain
Hospital Universitario de La Princesa

Madrid, 28006, Spain
Hospital Universitario de Salamanca

Salamanca, 37007, Spain
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo

São Paulo, 5403000, Brazil
Hotel Dieu

Nantes, Loire-Atlantique, 44093, France
Indiana University School of Medicine

Indianapolis, Indiana, 46202, United States
Institute of Hematology "Seragnoli" University of Bologna

Bologna, 40138, Italy
Irmandade Da Santa Casa de Misericordia de Sao Paulo

São Paulo, 01223-001, Brazil
Karmanos Cancer Institute

Detroit, Michigan, 48201, United States
Maastricht University Medical Center

AZ Maastricht, 620, Netherlands
Manchester Royal Infirmary

Manchester, MI3 9WL, United Kingdom
Mayo Clinic

Rochester, Minnesota, 05590, United States
Meir Medical Center

Kfar Saba, 44281, Israel
Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States
Oxford University Hospitals NHS Trust

Oxford, OX3 7L, United Kingdom
Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia
Princess Margaret Hospital

Toronto, Ontario, M5G2M9, Canada
Queen Elizabeth Hospital

Birmingham, B152TH, United Kingdom
Rabin Medical Center - PPDS

Petah Tikva, 49100, Israel
Rambam Health Corporation

Haifa, 31096, Israel
Rigshospitalet

Copenhagen, 2100, Denmark
Royal Free and University College Medical School

London, NW3 2P, United Kingdom
Samsung Medical Center - PPDS

Seoul, 135-710, South Korea
Seoul National University Hospital

Seoul, 110744, South Korea
Severance Hospital at Yonsei University Health System - PPDS

Seoul, 120-752, South Korea
Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia
The Catholic University of Korea, Seoul St Mary's Hospital

Seoul, 137-70, South Korea
Tom Baker Cancer Centre

Calgary, Alberta, T2N 4N2, Canada
Tufts Medical Center

Boston, Massachusetts, 00211, United States
Universitair Medisch Centrum Utrecht

Utrecht, 3508, Netherlands
Universitat Heidelberg

Heidelberg, 69120, Germany
Universitatsklinikum Hamburg Eppendorf

Hamburg, 20246, Germany
University General Hospital of Patras

Pátrai, Achaia, 26500, Greece
University of Chicago

Chicago, Illinois, 60637, United States
University of Cincinnati

Cincinnati, Ohio, 45267, United States
University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States
VU Medisch Centrum

Amsterdam, North Holland, 1081 HV, Netherlands
Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M, Canada
Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States
Vseobecna fakultni nemocnice v Praze

Prague, Praha, Hlavni Mesto, 128 08, Czechia
Washington University

St Louis, Missouri, 63110, United States
Westmead Hospital

Westmead, New South Wales, 214, Australia