Clinical Trial Details

NCT ID: NCT01659658
Date Last Changed: June 8, 2017

Overview

Research Study Summary

A clinical trial to evaluate treatments for patients with Relapsed or Refractory Systemic Light Chain Amyloidosis

Research Study 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

Purpose

The purpose of this study is to 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.

To Learn more

Recruitment Details

Phase
3
Gender
All
Age
18 and up
Overall Status
Recruiting
Lead Sponsor
Millennium Pharmaceuticals, Inc.
Duration
69 Months
Facility Type
N/A
Compensation

Eligibility

All ages 18 Years and up

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:

  3. Histochemical diagnosis of amyloidosis, as based on tissue specimens with Congo red staining with exhibition of an apple-green birefringence

  4. If clinical and laboratory parameters insufficient to establish AL amyloidosis or in cases of doubt, amyloid typing may be necessary.

  5. 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.

  6. Objective, measurable major (cardiac or renal) organ amyloid involvement as defined as follows (amyloid involvement of at least 1 required):

  7. 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.

  8. 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.

  1. 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.

  2. 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.)

  3. 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

  4. Must have recovered (ie, ≤ Grade 1 toxicity or participant's baseline status) from the reversible effects of prior therapy

  5. 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):

  7. Stage 1: both NT-proBNP and troponin T under threshold

  8. Stage 2: either NT-proBNP or troponin T (but not both) over threshold;

  9. Stage 3: both NT-proBNP and troponin T over threshold (but NT-proBNP < 8000 pg/mL)

  10. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2.

  11. Clinical laboratory values:

  12. Absolute neutrophil count ≥ 1000/µL

  13. Platelet count ≥ 75,000/µL

  14. 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

  15. Alkaline phosphatase ≤ 5 x ULN

  16. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤3 x ULN

  17. Calculated creatinine clearance ≥ 30 mL/min

  18. Female participants who:

  19. 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

  20. Must also adhere to the guidelines of any treatment-specific pregnancy prevention program, if applicable, OR

  21. 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.)

  4. 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:

  5. Bone lesions

  6. Hypercalcemia, defined as a calcium of > 11 mg/dL

  7. 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.

  8. 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.).

  9. 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.

  10. Ongoing or active infection, known human immunodeficiency virus (HIV) positive, active hepatitis B or C infection.

  11. Psychiatric illness/social situations that would limit compliance with study requirements.

  12. Known allergy to boron, MLN9708, any of the study treatments, their analogues, or excipients.

  13. 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.

  14. Diagnosed or treated for another malignancy within 3 years (5 years for sites 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.

Site Locations (59)

Country State City Zip Facility and Contact
United States Indiana Indianapolis 46202 Indiana University School of Medicine
United States Massachusetts Boston 2118 Boston Medical Center
United States Massachusetts Boston 211 Tufts Medical Center
United States Michigan Detroit 48201 Karmanos Cancer Institute
United States Minnesota Rochester 5590 Mayo Clinic
United States Missouri Saint Louis 63110-1093 Washington University
United States New York New York 10065 Memorial Sloan Kettering Cancer Center
United States Ohio Cincinnati 45267-0502 University of Cincinnati
United States Texas Dallas 75390 University of Texas Southwestern Medical Center
Australia New South Wales Westmead 214 Westmead Hospital
Australia Queensland Woolloongabba 4102 Princess Alexandra Hospital
Australia Victoria Box Hill 3128 Box Hill Hospital
Australia Western Australia Nedlands 6009 Sir Charles Gairdner Hospital
Brazil Santa Catarina Florianopolis 88034-000 Centro de Pesquisas Oncologicas
Brazil Rio de Janeiro 21941-913 Hospital Universitario Clementino Fraga Filho (UFRJ)
Brazil Sao Paulo 01223-001 Irmandade Da Santa Casa de Misericordia de Sao Paulo
Brazil Sao Paulo 05652-900 Hospital Israelita Albert Einstein
Brazil Sao Paulo 5403000 Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo
Canada Alberta Calgary T2N 4N2 Tom Baker Cancer Centre
Canada Alberta Edmonton T6G 1Z Cross Cancer Institute
Canada British Columbia Vancouver V5Z 1M Vancouver General Hospital
Canada Ontario Toronto M5G2M9 Princess Margaret Hospital
Czechia Moravskoslezsk kraj Ostrava 708 52 Fakultni nemocnice Ostrava
Czechia Praha, hlavni mesto Praha 128 08 Vseobecna fakultni nemocnice v Praze
Denmark Aahus 800 Arhus Universitetshospital Arhus Sygehus
Denmark Copenhagen 2100 Rigshospitalet
France Loire-Atlantique Nantes 44093 Hotel Dieu
France Lille 5903 Hopital Claude Huriez
France Limoges 87042 Centre Hospitalier et Universitaire de Limoges
France Paris 75010 Hopital Saint Louis
France Toulouse 31059 Hopital de Rangueil
Germany Berlin 12200 Charite - Universitatsmedizin Berlin
Germany Hamburg 20246 Universitatsklinikum Hamburg Eppendorf
Germany Heidelberg 69120 Universitat Heidelberg
Greece Achaia Patras 26500 University General Hospital of Patras
Greece Athens 11528 Alexandra Hospital
Israel Haifa 31096 Rambam Health Corporation
Israel Jerusalem 911 Hadasit Medical Research Services and Development Ltd
Israel Kfar Saba 44281 Meir Medical Center
Israel Petach Tikva 49100 Rabin Medical Center - PPDS
Israel Ramat-Gan 52621 Chaim Sheba Medical Center
Italy Bologna 40138 Institute of Hematology "Seragnoli" University of Bologna
Italy Pavia 2710 Fondazione IRCCS Policlinico San Matteo di Pavia
Korea, Republic of Incheon 405-760 Gachon University Gil Medical Center
Korea, Republic of Seoul 110744 Seoul National University Hospital
Korea, Republic of Seoul 120-752 Severance Hospital at Yonsei University Health System - PPDS
Korea, Republic of Seoul 135-710 Samsung Medical Center - PPDS
Korea, Republic of Seoul 137-70 The Catholic University of Korea, Seoul St Mary's Hospital
Netherlands Noord-Holland Amsterdam 1081 HV VU Medisch Centrum
Netherlands AZ Maastricht 620 Maastricht University Medical Center
Netherlands Utrecht 3508 Universitair Medisch Centrum Utrecht
Spain Navarra Pamplona 31008 Clinica Universidad de Navarra
Spain Barcelona 8036 Hospital Clinic de Barcelona
Spain Madrid 28006 Hospital Universitario de La Princesa
Spain Majadahonda 28222 Hospital Universitario Puerta de Hierro - Majadahonda
Spain Salamanca 37007 Hospital Universitario de Salamanca
United Kingdom Birmingham B152TH Queen Elizabeth Hospital
United Kingdom London NW3 2P Royal Free and University College Medical School
United Kingdom Manchester MI3 9WL Manchester Royal Infirmary

Contact

Takeda Study Registration Call Center
+1-844-662-8532
E-mail:

DISCLAIMER: CenterWatch does not conduct clinical research. CenterWatch is a publishing company that posts clinical trials information on behalf of sponsor companies, contract research organizations, clinical research sites and other interested parties. This information is designed to help patients find clinical trials of interest and contact the research centers conducting the trials.