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AzTrials

Relapsed or Refractory Systemic Light Chain AmyloidosisPhase 3NCT01659658

Study of Dexamethasone Plus IXAZOMIB (MLN9708) or Physicians Choice of Treatment in Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis

A Phase 3 study testing IXAZOMIB, Dexamethasone and Melphalan in people with Relapsed or Refractory Systemic Light Chain Amyloidosis, run by Millennium Pharmaceuticals, Inc. at 66 sites in 15 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
IXAZOMIB, Dexamethasone and Melphalan
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
177 participants
Where
66 sitesin 15 countries
Study dates
26 Dec 2012to 11 Jul 2022
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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):
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  • 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):
  • Stage 1: both NT-proBNP and troponin T under threshold
  • Stage 2: either NT-proBNP or troponin T (but not both) over threshold;
  • Stage 3: both NT-proBNP and troponin T over threshold (but NT-proBNP < 8000 pg/mL)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.
  • Clinical laboratory values:
  • Absolute neutrophil count ≥ 1000/µL
  • Platelet count ≥ 75,000/µL
  • 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
  • Alkaline phosphatase ≤ 5 x ULN
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3 x ULN
  • Calculated creatinine clearance ≥ 30 mL/min
  • Female participants who:
  • 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
  • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
  • 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:
  • Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, AND
  • Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR
  • 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.)
  • 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.

Who cannot join

  • 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
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  • 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.

Trial locations and contacts

66 sites in 15 countries.

66 sites in 15 countries

United States15 sites

  • Tufts Medical Center

    Boston, Massachusetts, 00211

  • Boston Medical Center

    Boston, Massachusetts, 02118

  • University of Chicago

    Chicago, Illinois, 60637

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • Indiana University School of Medicine

    Indianapolis, Indiana, 46202

  • Cedars Sinai Medical Center

    Los Angeles, California, 90048

  • Froedtert and The Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232

  • Columbia University Medical Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Mayo Clinic

    Rochester, Minnesota, 05590

  • Washington University

    St Louis, Missouri, 63110

Other trials in United States

Brazil5 sites

  • Centro de Pesquisas Oncologicas

    Florianópolis, Santa Catarina, 88034-000

  • Hospital Universitario Clementino Fraga Filho (UFRJ)

    Rio de Janeiro, 21941-913

  • Irmandade Da Santa Casa de Misericordia de Sao Paulo

    São Paulo, 01223-001

  • Hospital Israelita Albert Einstein

    São Paulo, 05652-900

  • Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo

    São Paulo, 5403000

Other trials in Brazil

France5 sites

  • Hopital Claude Huriez

    Lille, 5903

  • Centre Hospitalier et Universitaire de Limoges

    Limoges, 87042

  • Hotel Dieu

    Nantes, Loire-Atlantique, 44093

  • Hopital Saint Louis

    Paris, 75010

  • Hopital de Rangueil

    Toulouse, 31059

Other trials in France

Israel5 sites

  • Rambam Health Corporation

    Haifa, 31096

  • Hadasit Medical Research Services and Development Ltd

    Jerusalem, 911

  • Meir Medical Center

    Kfar Saba, 44281

  • Rabin Medical Center - PPDS

    Petah Tikva, 49100

  • Chaim Sheba Medical Center

    Ramat Gan, 52621

Other trials in Israel

South Korea5 sites

  • Gachon University Gil Medical Center

    Incheon, 405-760

  • Seoul National University Hospital

    Seoul, 110744

  • Severance Hospital at Yonsei University Health System - PPDS

    Seoul, 120-752

  • Samsung Medical Center - PPDS

    Seoul, 135-710

  • The Catholic University of Korea, Seoul St Mary's Hospital

    Seoul, 137-70

Other trials in South Korea

Spain5 sites

  • Hospital Clinic de Barcelona

    Barcelona, 8036

  • Hospital Universitario de La Princesa

    Madrid, 28006

  • Hospital Universitario Puerta de Hierro - Majadahonda

    Majadahonda, 28222

  • Clinica Universidad de Navarra

    Pamplona, Navarre, 31008

  • Hospital Universitario de Salamanca

    Salamanca, 37007

Other trials in Spain

Australia4 sites

  • Box Hill Hospital

    Box Hill, Victoria, 3128

  • Sir Charles Gairdner Hospital

    Nedlands, Western Australia, 6009

  • Westmead Hospital

    Westmead, New South Wales, 214

  • Princess Alexandra Hospital

    Woolloongabba, Queensland, 4102

Other trials in Australia

Canada4 sites

  • Tom Baker Cancer Centre

    Calgary, Alberta, T2N 4N2

  • Cross Cancer Institute

    Edmonton, Alberta, T6G 1Z

  • Princess Margaret Hospital

    Toronto, Ontario, M5G2M9

  • Vancouver General Hospital

    Vancouver, British Columbia, V5Z 1M

Other trials in Canada

United Kingdom4 sites

  • Queen Elizabeth Hospital

    Birmingham, B152TH

  • Royal Free and University College Medical School

    London, NW3 2P

  • Manchester Royal Infirmary

    Manchester, MI3 9WL

  • Oxford University Hospitals NHS Trust

    Oxford, OX3 7L

Other trials in United Kingdom

Germany3 sites

  • Charite - Universitatsmedizin Berlin

    Berlin, 12200

  • Universitatsklinikum Hamburg Eppendorf

    Hamburg, 20246

  • Universitat Heidelberg

    Heidelberg, 69120

Other trials in Germany

Netherlands3 sites

  • VU Medisch Centrum

    Amsterdam, North Holland, 1081 HV

  • Maastricht University Medical Center

    AZ Maastricht, 620

  • Universitair Medisch Centrum Utrecht

    Utrecht, 3508

Other trials in Netherlands

Czechia2 sites

  • Fakultni nemocnice Ostrava

    Ostrava, Moravskoslezsk Kraj, 708 52

  • Vseobecna fakultni nemocnice v Praze

    Prague, Praha, Hlavni Mesto, 128 08

Other trials in Czechia

Denmark2 sites

  • Arhus Universitetshospital Arhus Sygehus

    Aahus, 800

  • Rigshospitalet

    Copenhagen, 2100

Other trials in Denmark

Greece2 sites

  • Alexandra Hospital

    Athens, 11528

  • University General Hospital of Patras

    Pátrai, Achaia, 26500

Other trials in Greece

Italy2 sites

  • Institute of Hematology "Seragnoli" University of Bologna

    Bologna, 40138

  • Fondazione IRCCS Policlinico San Matteo di Pavia

    Pavia, 2710

Other trials in Italy

About this study

Official title: 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

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.

Read the detailed description

The drug being tested in this study is called IXAZOMIB. IXAZOMIB was being tested to treat people who have relapsed or Refractory Systemic Light Chain (AL) Amyloidosis.

The study will enroll approximately 177 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups:

  • IXAZOMIB 4 mg plus Dexamethasone 20 mg
  • Physician's choice: Participants will receive one of the following treatment options as selected by the physician:
  1. Dexamethasone 20 mg
  2. Dexamethasone 20 mg + Melphalan 0.22 mg/kg
  3. Dexamethasone 20 mg + Cyclophosphamide 500 mg
  4. Dexamethasone 20 mg + Thalidomide 200 mg
  5. Dexamethasone 20 mg + Lenalidomide 15 mg
  6. All participants will be asked to take oral formulation of the drugs. In both treatment arms, each participant will continue to receive sequential cycles of therapy until disease progression, unacceptable toxicity, or until the study is terminated, whichever occurs first. Participants in Arm B receiving melphalan and dexamethasone will be treated to best response plus 2 additional cycles.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is 120 months (10 years), including 84 months of enrollment and 36 months of follow-up after the last participant is enrolled.

Keywords
MLN9708, Amyloidosis, Light Chain, IXAZOMIB, Tourmaline AL1, Drug Therapy
Medical subject headings
Recurrence, Amyloidosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT01659658
Study groupRoleWhat they receive
Arm A: Ixazomib + DexamethasoneExperimentalIxazomib 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.
Receives: Drug: IXAZOMIB; Drug: Dexamethasone
Arm B: Dexamethasone + MelphalanActive 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.
Receives: Drug: Dexamethasone; Drug: Melphalan
Arm B: Dexamethasone + CyclophosphamideActive 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.
Receives: Drug: Dexamethasone; Drug: Cyclophosphamide
Arm B: Dexamethasone + ThalidomideActive 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.
Receives: Drug: Dexamethasone; Drug: Thalidomide
Arm B: Dexamethasone + LenalidomideActive 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.
Receives: Drug: Dexamethasone; Drug: Lenalidomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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. 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.

    Measured: Up to 2 years

Secondary outcomes (19)

  1. Percentage of Participants With Complete Hematologic Response

    Complete hematologic response was defined as the percentage of participants with CR based on central laboratory results and the 2010 ISA Consensus Criteria as assessed by the investigator. CR: Complete disappearance of M-protein from serum and urine on immunofixation, and normalization of FLC ratio. 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.

    Measured: 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. Overall Survival

    Overall survival was defined as the time from the date of randomization to the date of death. 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.

    Measured: 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)

  3. Progression Free Survival (PFS)

    PFS was defined as the time from the date of randomization to the date of first documentation of hematologic disease progression, or organ (cardiac or renal) progression, or death due to any cause, whichever occurred first according to central laboratory results and ISA criteria as evaluated by the investigator. 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.

    Measured: 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)

  4. Hematologic Disease Progression Free Survival

    Hematologic disease PFS was defined as the time from the date of randomization to the date of first documentation of hematologic PD according to central laboratory results and ISA criteria as evaluated by an adjudication committee, or death due to any cause, whichever occurred first. 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.

    Measured: 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)

  5. Time to Vital Organ (Heart or Kidney) Deterioration and Mortality Rate

    Time to vital organ deterioration or death was assessed by the investigator and defined as the time from randomization to vital organ (heart or kidney) deterioration or death, whichever occurs first. Cardiac deterioration is defined as the need for hospitalization for heart failure. Kidney deterioration is defined as progression to ESRD with the need for maintenance dialysis or renal transplantation. 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.

    Measured: From randomization to time of vital organ deterioration or death (up to 115 months)

  6. Percentage of Participants With Best Vital Organ (Cardiac and/or Kidney) Response

    Vital organ (heart and kidney) response rate was defined as the percentage of participants who achieved vital organ response according to central laboratory results and ISA criteria as evaluated by an adjudication committee. A vital organ response was defined as response of 1 or 2 of the involved vital organs with no change from Baseline in the rest of involved vital organs. 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.

    Measured: 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)

  7. Vital Organ Progression Free Survival

    Vital organ PFS is defined as the time from the date of randomization to the date of first documentation of progression of vital organ (heart or kidney) according to central laboratory results and ISA criteria as evaluated by an adjudication committee, or death due to any cause, whichever occurs first. 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.

    Measured: 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)

  8. Duration of Hematologic Response

    Duration of hematologic response (DOR) was defined as the time from the date of first documentation of a hematologic response to the date of first documented hematologic disease progression as determined by the investigator. 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.

    Measured: From time of first documented response to disease progression (up to 115 months)

  9. Number of Participants With Serious Adverse Events (SAEs)

    A SAE was defined as any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of an existing hospitalization, resulted in persistent or significant disability or incapacity, was a congenital anomaly/birth defect or medically important event.

    Measured: From first dose of study drug through 30 days after administration of the last dose of study drug (up to 115 months)

  10. Time To Treatment Failure (TTF)

    TTF was defined as the time from randomization to the date of first documented treatment failure. Treatment failure was defined as: 1) death due to any cause; 2) hematologic progression or major organ progression according to central laboratory results and ISA criteria as evaluated by the investigator; 3) clinically morbid organ disease requiring additional therapy; or 4) withdrawn for any reason. 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.

    Measured: 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)

  11. Time To Subsequent Anticancer Treatment

    Time to subsequent anticancer therapy was defined as the time from randomization to the first date of subsequent anticancer therapy. Participants without subsequent anticancer therapy were censored at the date of death or last known to be alive. 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.

    Measured: From first dose of study drug until subsequent anticancer treatment (up to 115 months)

  12. Change From Baseline in 36-item Short Form General Health Survey (SF-36) Mental Component Summary Score at Week 28 of the PFS Follow-up

    SF-36 Version 2 is a multipurpose, participant completed, short-form health survey with 36 questions that consists of an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Physical component summary (PCS) is mostly contributed by physical function (PF), role physical (RP), bodily pain (BP), and general health (GH). Mental component summary (MCS) is mostly contributed by mental health (MH), role emotional (RE), social function (SF), and vitality (VT). Each component on the SF-36 item health survey is scored from 0 (best) to 100 (worst). Total score ranges from 0-100, where higher scores are associated with less disability and better quality of life. 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.

    Measured: Baseline, Week 28 of the PFS Follow-up

  13. Change From Baseline in SF-36 Physical Component Summary Score at Week 28 of the PFS Follow-up

    SF-36 Version 2 is a multipurpose, participant completed, short-form health survey with 36 questions that consists of an 8-scale profile of functional health and well-being scores as well as psychometrically-based physical and mental health summary measures. Physical component summary (PCS) is mostly contributed by physical function (PF), role physical (RP), bodily pain (BP), and general health (GH). Mental component summary (MCS) is mostly contributed by mental health (MH), role emotional (RE), social function (SF), and vitality (VT). Each component on the SF-36 item health survey is scored from 0 (best) to 100 (worst). Total score ranges from 0-100, where higher scores are associated with less disability and better quality of life. 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.

    Measured: Baseline, Week 28 of the PFS Follow-up

  14. Change From Baseline in Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) Score at Week 28 of the PFS Follow-up

    The FACT/GOG-Ntx is a participant completed questionnaire that comprises 11 individual items evaluating symptoms of neurotoxicity on a 5-point scale where: 0=not at all (best) to 4=very much for a total possible score of 0 to 44. Symptom scores are inverted so that higher scores of FACT/GOG-Ntx indicate higher quality of life or functioning. 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.

    Measured: Baseline, Week 28 of the PFS Follow-up

  15. Change From Baseline in Amyloidosis Symptom Scale Total Score at Week 28 of the PFS Follow-up

    The amyloidosis symptom scale questionnaire is a participant completed questionnaire that evaluates symptom severity of 3 symptoms: Swelling, Shortness of Breath and Dizziness, each rated on an 11-point scale where: 0=no symptoms to 10=very severe symptoms. Higher scores indicate worsening of symptoms. Total Score is the sum of all responses from the amyloidosis symptom scale ranging from 0 to 30. Higher scores represent higher levels of symptomatology or problems and a negative change from baseline indicates improvement. 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.

    Measured: Baseline, Week 28 of the PFS Follow-up

  16. Number of Participants in Each Category of the EuroQol 5-Dimensional (EQ-5D) Questionnaire Score

    The European Quality of Life (EuroQOL) 5-Dimensional (EQ-5D) is a patient completed questionnaire consisting of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression). Each dimension has 3 possible choices: no problems to extreme problems. Higher scores=worsening of the quality of life. 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.

    Measured: At Week 28 of the OS follow-up

  17. EuroQol 5-Dimension 3-Level (EQ-5D-3L) Visual Analogue Scale Score

    The EQ visual analogue scale (VAS) records the participant's self-rated health on a 20 centimeter vertical VAS that ranges from 0 (worst imaginable health state) to 100 (best imaginable health state). Baseline is defined as the value collected at the time closest to, but prior to, the start of study drug administration. 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.

    Measured: At Week 28 of the OS follow-up

  18. Plasma Concentration of Ixazomib

    As prespecified in the protocol, data for this outcome measure was planned to be collected for ixazomib arm group only.

    Measured: Cycle 1, Day 1: 1, 4 hours postdose, Day 14: 144 hours postdose; Cycle 2, Day 1: predose, Day 14: 144 hours postdose; Cycles 3 to 10, Day 1: predose (cycle length=28 days)

  19. Number of Hospitalizations

    A hospitalization was defined as at least one overnight stay in an intensive care unit and/or non-intensive care unit. If a single hospitalization included both an intensive care unit stay and a non-intensive care unit stay, the hospitalization was counted only once (as an intensive care unit stay). The mean number of hospitalizations is reported in this outcome measure. 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.

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Aug 2012 (estimated)
  2. Study start26 Dec 2012
  3. Primary completion11 Jul 2022
  4. Study completion11 Jul 2022

Why it stopped: Sponsor's decision

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
177 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01659658
Sponsor's protocol ID
C16011
Other IDs
2011-005468-10, U1111-1164-7621, C16011-CTIL, NL41603.028.12, 12/LO/1771, MOH_2017-05-07_000374
Status last verified
Aug 2025
First submitted
2 Aug 2012
Last updated
2 Sep 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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.

Publications

  • 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.

    PubMed 36708469

  • Sanchorawala 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.

    PubMed 28550039

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing IXAZOMIB, Dexamethasone and Melphalan in people with Relapsed or Refractory Systemic Light Chain Amyloidosis, run by Millennium Pharmaceuticals, Inc. at 66 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 2 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 66 sites in United States, Brazil, France, Israel, South Korea and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Sep 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With Overall Hematologic Response (time frame: 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)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01659658, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2025.

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