AL Amyloidosis Clinical Trial

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

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.

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Full 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:

Dexamethasone 20 mg
Dexamethasone 20 mg + Melphalan 0.22 mg/kg
Dexamethasone 20 mg + Cyclophosphamide 500 mg
Dexamethasone 20 mg + Thalidomide 200 mg
Dexamethasone 20 mg + Lenalidomide 15 mg
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.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

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):

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.

Exclusion Criteria:

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.

Study is for people with:

AL Amyloidosis

Phase:

Phase 3

Estimated Enrollment:

177

Study ID:

NCT01659658

Recruitment Status:

Terminated

Sponsor:

Millennium Pharmaceuticals, Inc.

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There are 66 Locations for this study

See Locations Near You

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
Saint 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
Florianopolis Santa Catarina, 88034, Brazil
Hospital Universitario Clementino Fraga Filho (UFRJ)
Rio de Janeiro , 21941, Brazil
Irmandade Da Santa Casa de Misericordia de Sao Paulo
Sao Paulo , 01223, Brazil
Hospital Israelita Albert Einstein
Sao Paulo , 05652, Brazil
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
Sao Paulo , 54030, Brazil
Tom Baker Cancer Centre
Calgary Alberta, T2N 4, Canada
Cross Cancer Institute
Edmonton Alberta, T6G 1, Canada
Vancouver General Hospital
Vancouver British Columbia, V5Z 1, Canada
Princess Margaret Hospital
Toronto Ontario, M5G2M, Canada
Fakultni nemocnice Ostrava
Ostrava Moravskoslezsk Kraj, 708 5, Czechia
Vseobecna fakultni nemocnice v Praze
Praha Praha, Hlavni Mesto, 128 0, 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
Patras 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
Petach 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
Gachon University Gil Medical Center
Incheon , 405-7, Korea, Republic of
Seoul National University Hospital
Seoul , 11074, Korea, Republic of
Severance Hospital at Yonsei University Health System - PPDS
Seoul , 120-7, Korea, Republic of
Samsung Medical Center - PPDS
Seoul , 135-7, Korea, Republic of
The Catholic University of Korea, Seoul St Mary's Hospital
Seoul , 137-7, Korea, Republic of
VU Medisch Centrum
Amsterdam Noord-Holland, 1081 , Netherlands
Maastricht University Medical Center
AZ Maastricht , 620, Netherlands
Universitair Medisch Centrum Utrecht
Utrecht , 3508, Netherlands
Clinica Universidad de Navarra
Pamplona Navarra, 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 , B152T, United Kingdom
Royal Free and University College Medical School
London , NW3 2, United Kingdom
Manchester Royal Infirmary
Manchester , MI3 9, United Kingdom
Oxford University Hospitals NHS Trust
Oxford , OX3 7, United Kingdom

How clear is this clinincal trial information?

Study is for people with:

AL Amyloidosis

Phase:

Phase 3

Estimated Enrollment:

177

Study ID:

NCT01659658

Recruitment Status:

Terminated

Sponsor:


Millennium Pharmaceuticals, Inc.

How clear is this clinincal trial information?

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