Ixazomib Maintenance Study in Patients With AL Amyloidosis

Inclusion Criteria:

1. Male or female patients 18 years or older.

2. Biopsy-proven diagnosis of AL amyloidosis at the enrolling institution, according to
the following standard criteria:

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

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

- Measurable disease as defined by serum differential free light chain
concentration (dFLC, difference between amyloid forming [involved] and non
amyloid forming [uninvolved] free light chain [FLC]) ≥ 50 mg/L) (or M-protein of
0.5g/dl) prior to initial therapy.

- At least one organ involved with AL amyloidosis including renal, cardiac,
GI/Liver, peripheral/autonomic nervous system and/or soft tissue disease (Comenzo
et al. Leukemia 2012).

3. At least a hematologic partial response (PR) defined by the updated AL response
criteria (Pallidini et al. JCO 2012) to one line of initial therapy (may include
induction followed by autologous stem cell transplant (ASCT)).

4. Patients must have >10% bone marrow plasma cells (on aspirate or biopsy) at initial
diagnosis.

5. At least 2 cycles of any induction therapy (that may include alkylators,
corticosteroids, proteosome inhibitors, IMIDs - including in combination) or upfront
ASCT (with or without preceding induction). Patients who receive ixazomib as part of
initial therapy are eligible.

6. Patients must be within 12 months of the start of initial therapy.

7. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.

8. Female patients who:

- Are postmenopausal for at least 1 year before the screening visit, OR

- Are surgically sterile, OR

- 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
form through 90 days after the last dose of study drug, AND

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

- Agree to practice true abstinence when this is in line with the preferred and
usual lifestyle of the subject. (Periodic abstinence [e.g., calendar, ovulation,
symptothermal, post-ovulation methods] and withdrawal are not acceptable methods
of contraception.)

- Have a negative serum pregnancy test done ≤ 7 days prior to registration, for
women of childbearing potential only

9. Male patients, even if surgically sterilized (i.e., status post-vasectomy), must agree
to one of the following:

- Agree to practice effective barrier contraception during the entire study
treatment period and through 90 days after the last dose of study drug, OR

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

- Agree to practice true abstinence when this is in line with the preferred and
usual lifestyle of the subject. (Periodic abstinence (e.g., calendar, ovulation,
symptothermal, post-ovulation methods] and withdrawal are not acceptable methods
of contraception.)

10. Patients must meet the following clinical laboratory criteria:

- Absolute neutrophil count (ANC) ≥ 1,000/mm^3

- Platelet count ≥ 75,000/mm^3

- Hemoglobin ≥ 8.0 g/dL

- Platelet transfusions to help patients meet eligibility criteria are not allowed
within 3 days before study enrollment.

- Total bilirubin ≤ 2 x the upper limit of the normal range (ULN) (except in
patients with Gilbert‟s syndrome who must have a total bilirubin of < 3 x ULN).

- ALT/AST < 2.5x the upper limit of normal

Exclusion Criteria:

1. Female patients who are lactating or have a positive serum pregnancy test during the
screening period.

2. Patients with primary refractory AL amyloidosis (< PR to initial therapy).

3. Patients resistant and/or refractory to proteosome inhibitors.

4. Active multiple myeloma with end organ damage (CRAB criteria).

5. Evidence of current uncontrolled cardiovascular conditions, including uncontrolled
hypertension, uncontrolled cardiac arrhythmias, symptomatic congestive heart failure
(NYHA class III/IV), unstable angina, or myocardial infarction within the past 6
months.

6. Active systemic infection, including active hepatitis B or C virus infection. Patients
who are human immunodeficiency virus (HIV) infected can be enrolled as long as CD4 is
above 350, viral load has been undetectable for more than 6 months on stable
anti-retroviral therapy, no previous AIDS-defining illness, and there is agreement
with the HIV-treating physician that the patients can be monitored for possible
treatment failure. Eligibility will be confirmed by the MSK Principal Investigator
(PI).

7. Any serious medical or psychiatric illness that could, in the investigator‟s opinion,
potentially interfere with the completion of treatment according to this protocol.

8. Systemic treatment, within 14 days before the first dose of ixazomib with strong CYP3A
inducers (rifampin, rifapentine, rifabutin, carbamazepine, phenytoin, phenobarbital),
or use of St. John‟s wort.

9. Known allergy to any of the study medications, their analogues, or excipients in the
various formulations of any agent.

10. Known GI disease or GI procedure that could interfere with the oral absorption or
tolerance of ixazomib including difficulty swallowing.

11. Diagnosed or treated for another malignancy within 2 years before study enrollment or
previously diagnosed with another malignancy and have any evidence of residual
disease. Patients with early stage prostate cancer, non melanoma skin cancer or
carcinoma in situ of any type are not excluded; patients with malignancies that have
undergone complete resection are not excluded.

12. Patient has > Grade 2 peripheral neuropathy, or Grade 1 with pain (not controlled with
medical therapy) on clinical examination during the screening period.

13. Participation in other clinical trials, including those with other investigational
agents not included in this trial, within 21 days of the start of this trial and
throughout the duration of this trial.