Clinical Trial Details

NCT ID: NCT01659658
Date Last Changed: February 23, 2016

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.

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Recruitment Details

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

Eligibility

Both Male and Female 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 (62)

Country State City Zip Facility and Contact
United States California Los Angeles Research Site
United States Colorado Denver Research Site
United States Illinois Chicago Research Site
United States Indiana Indianapolis Research Site
United States Massachusetts Boston Research Site
United States Michigan Detroit Research Site
United States Minnesota Rochester Research Site
United States Missouri St Louis Research Site
United States New York New York Research Site
United States North Carolina Charlotte Research Site
United States Ohio Cincinnati Research Site
United States Ohio Cleveland Research Site
United States Tennessee Nashville Research Site
United States Texas Dallas Research Site
United States Wisconsin Milwaukee Research Site
Australia New South Wales Westmead Research Site
Australia Queensland Woolloongabba Research Site
Australia Victoria Box Hill Research Site
Australia Western Australia Nedlands Research Site
Brazil Santa Catarina Florianopolis Research Site
Brazil Sao Paulo Sao Paulo - Sp Research Site
Brazil Rio de Janeiro Research Site
Brazil Sao Paulo Research Site
Canada Alberta Calgary Research Site
Canada Alberta Edmonton Research Site
Canada British Columbia Vancouver Research Site
Canada Ontario Toronto Research Site
Czech Republic Praha, hlavni mesto Praha Research Site
Czech Republic Ostrava Research Site
Denmark Aarhus Research Site
Denmark Copenhagen Research Site
France Loire-Atlantique Nantes Research Site
France Lille Research Site
France Limoges Cedex Research Site
France Paris 10 Research Site
France Toulouse Cedex 9 Research Site
Germany Berlin Research Site
Germany Hamburg Research Site
Germany Heidelberg Research Site
Greece Achaia Patra Research Site
Greece Athens Research Site
Israel Haifa Research Site
Israel Jerusalem Research Site
Israel Kfar Saba Research Site
Israel Petah-Tiqva Research Site
Israel Ramat-gan Research Site
Italy Lombardia Pavia Research Site
Italy Bologna Research Site
Korea, Republic of Incheon Research Site
Korea, Republic of Seoul Research Site
Netherlands Noord-Holland Amsterdam Research Site
Netherlands AZ Maastricht Research Site
Netherlands Utrecht Research Site
Spain Castilla y Le0n Salamanca Research Site
Spain Cataluna Barcelona Research Site
Spain Madrid Majadahonda Research Site
Spain Navarra Pamplona Research Site
Spain Madrid Research Site
United Kingdom Oxfordshire Oxford Research Site
United Kingdom Birmingham Research Site
United Kingdom London Research Site
United Kingdom Manchester Research Site

Contact

Takeda Study Registration Call Center
+1-877-825-3327
E-mail:

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