A Phase 3, Randomized, Controlled, Open-label, Multicenter, Safety and Efficacy Study of Dexamethasone Plus MLN9708 or Physician's Choice of Treatment Administered to Patients With Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis
Rochester, Minn., Phoenix/Scottsdale, Ariz.
Trial status: Open for Enrollment
Why is this study being done?
This is a phase 3, randomized, controlled, open-label, multicenter study of the oral formulation of dexamethasone plus MLN9708 compared with treatment chosen by the investigator from a prespecified list of regimens available in clinical practice. Treatment options will include: dexamethasone alone, dexamethasone plus an alkylating agent (melphalan or cyclophosphamide), or dexamethasone plus an immunomodulatory drug (IMiD, thalidomide or lenalidomide) in patients with relapsed or refractory AL amyloidosis. Crossover to the investigational treatment arm is not permitted during participation in this study.
Who is eligible to participate?
- Male or female patients 18 years or older
- Biopsy-proven AL amyloidosis with relapsed or refractory disease despite 1 or 2 prior therapies. Patients may be proteasome inhibitor-exposed or naive, but cannot be refractory to proteasome inhibitor therapy
- Disease requiring further treatment
- Measurable disease as defined by serum differential free light chain concentration (dFLC)
- Objective and measurable major organ involvement (ie, cardiac or renal) as defined by the standard International Society of Amyloidosis (ISA) criteria.
- Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to 2
- Meet the clinical laboratories criteria as specified in the protocol
- Female patients who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception through 90 days after the last dose of study treatment or agree to practice true abstinence; must also adhere to the guidelines of any treatment specific pregnancy prevention program
- Male patients who agree to practice effective barrier contraception through 90 days after the last dose of study treatment or agree to practice true abstinence AND must adhere to the guidelines of any treatment specific pregnancy prevention program
- Voluntary written consent
- Amyloidosis due to mutations of the transthyretin gene or presence of other non-AL amyloidosis
- Female patients who are lactating, breastfeeding or pregnant
- Evidence of current uncontrolled cardiovascular conditions as specified in study protocol
- Clinically overt multiple myeloma as specified in study protocol
- Inability to swallow 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, patients may be on chronic steroids (maximum dose 20 mg/day prednisone or equivalent if they are being given for disorders other than amyloidosis
- Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient 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 HIV positive, active hepatitis B or C infection
- Psychiatric illness/social situations that would limit compliance with study requirements
- Known allergy to any of the study medications, their analogues or excipients
- Systemic treatment with strong inhibitors of CYP1A2, strong inhibitors of CYP3A, or strong CYP3A inducers, 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 5 years before study enrollment or previously diagnosed with another malignancy and have any evidence of residual disease. Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection