Study of Oral Ixazomib in Adult Participants With Relapsed or Refractory Light Chain Amyloidosis

An Open-Label, Dose-Escalation, Phase 1 Study of the Oral Formulation of MLN9708 Administered Weekly in Adult Patients With Relapsed or Refractory Light-Chain (AL) Amyloidosis Who Require Further Treatment

This study will include participants with previously treated systemic relapsed or refractory light-chain (AL) amyloidosis who require further therapy and will be aimed at determining the safety profile and the maximum tolerated dose/recommended phase 2 dose of MLN9078 (Ixazomib) administered orally.

Inclusion Criteria:

• Male or female participants 18 years or older
• Biopsy-proven systemic relapsed or refractory light-chain (AL) amyloidosis, which after at least 1 prior therapy, in the investigator's opinion, requires further treatment
• If received stem cell transplant, must be at least 3 months posttransplantation and recovered from side effects
• Must have measurable disease defined as serum differential free light chain concentration ≥ 40 mg/L
• Must have objective measurable organ (heart or kidney) amyloid involvement
• Must have cardiac biomarker risk stage I or II disease
• Must have adequate hematologic, hepatic, and renal function
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
• Female participants who are postmenopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to abstain from heterosexual intercourse
• Male participants who agree to practice effective barrier contraception or agree to abstain from heterosexual intercourse
• Voluntary written consent

Exclusion Criteria

• Peripheral neuropathy that is greater or equal to Grade 2
• Cardiac status as described in protocol
• Severe diarrhea (≥ Grade 3) not controllable with medication or requires administration of total parenteral nutrition
• Known gastrointestinal condition or procedure that could interfere with swallowing or the oral absorption of tolerance of MLN9708
• Uncontrolled infection requiring systematic antibiotics
• Known human immunodeficiency virus (HIV) positive, hepatitis B surface antigen-positive status, or known or suspected active hepatitis C infection
• Presence of other active malignancy with the exception of nonmelanoma skin cancer, cervical cancer, treated early-stage prostate cancer provided that prostate-specific antigen is within normal limit, or any completely resected carcinoma in situ
• Female participants who are lactating or pregnant
• Major surgery within 14 days before the first dose of study drug
• Serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol