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

Study ID
C16011

Cancer Related
Yes

Healthy Volunteers
No

Study Sites

  • Clements University Hospital
  • UT Southwestern Ambulatory Services
  • Zale Lipshy University Hospital
  • Parkland Health & Hospital System

Contact
James Pond
214/648-7030
blake.pond@utsouthwestern.edu

Principal Investigator
Larry Anderson

Official Title

A Phase 3, Randomized, Controlled, Open-label, Multicenter, Safety and Efficacy Study of Dexamethasone Plus IXAZOMIB (MLN9708) or Physicians Choice of Treatment Administered to Patients With Relapsed or Refractory Systemic Light Chain (AL) Amyloidosis

Brief Overview


This is a phase 3, randomized, controlled, open-label, multicenter study of the oral
formulation of dexamethasone plus IXAZOMIB 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.

Participant Eligibility


Inclusion Criteria:

- 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

Exclusion Criteria:

- 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