A Phase I/II Trial of Pomalidomide and Dexamethasone in Subjects With Previously-Treated AL Amyloidosis

Primary objective:

Determine dose-limiting toxicity (DLT) and the maximal tolerated dose (MTD) of pomalidomide
combined with dexamethasone in subjects with previously- treated light-chain (AL)-amyloidosis

Secondary objectives:

Determine the following at the MTD:

- Hematological complete (CR) very good partial (VGPR) and partial (PR) rates

- duration of response

- organ response

- Time-to-event

- Survival

Exploratory study objective:

To investigate the relationship of changes in the levels of the biomarkers B-type natriuretic
peptide (BNP) and troponin I to frequency of specific adverse events and the occurrence of
DLT

Inclusion Criteria:

1. Understand and voluntarily sign informed consent form.

2. ≥18yrs old

3. Able to adhere to the study visit schedule and other protocol requirements.

4. Biopsy proven tissue amyloid deposits or positive fat aspirate

5. Proof of AL type (a or b)

6. Measurable plasma cell dyscrasia (a or b and c of the following required):

1. Monoclonal protein in the serum or urine by immunofixation electrophoresis

2. Plasmacytosis of bone marrow (<30% plasma cells) with monoclonal staining for
kappa or lambda light-chain isotype

3. dFLC of 50mg/L (dFLC=difference in involved and uninvolved serum free light-chain
levels)

7. Must have received ≥1 prior treatment for AL amyloidosis, if it is intensive
chemotherapy and an autotransplant it must be ≥6 months prior to enrollment on this
study

8. Must have recovered from the reversible side effects of any prior therapy; permanent
and stable side effects/changes are acceptable. Prior treatment for AL amyloidosis
with chemotherapy, thalidomide, lenalidomide or steroids is not an exclusion

9. Eastern Cooperative Group (ECOG) performance status ≤2 at study entry

10. Lab test results within these ranges:

d. Neutrophil ≥1.5 x10e9/L e. Platelets ≥100x10e9/L f. Total bilirubin <1.5mg/dL g.
Aspartate aminotransferase (AST or SGOT) and Alanine Aminotransferase (ALT or SGPT) <
2 x Upper limit of normal h. Serum creatinine <2.5mg/dL

11. Disease free of prior malignancies for at least 5yrs with exception of currently
treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in-situ" of the
cervix or breast.

12. Females of childbearing potential (FCBP) (a FCBP is a sexually mature woman who has
not undergone a hysterectomy or bilateral oophorectomy, or has not been naturally
postmenopausal for at least 24 consecutive months) must have a negative serum or urine
pregnancy test with a sensitivity ≥ 50 milli-International unit/mL 10-14 days prior to
and again ≤ 24 hours of starting pomalidomide and must either commit to continued
abstinence from heterosexual intercourse or begin two (2) acceptable methods of birth
control, one highly effective method and one additional effective method AT THE SAME
TIME, ≥ 28 days before she starts taking pomalidomide. FCBP must also agree to ongoing
pregnancy testing. Men must agree to use a latex condom during sexual contact with a
FCBP even if they have had a vasectomy. All subjects must be counseled at a minimum of
every 28 days about pregnancy precautions and risks of fetal exposure.

13. Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (subjects
intolerant to aspirin may use warfarin or low molecular weight heparin).

Exclusion Criteria:

1. Secondary or familial amyloidosis

2. Multiple myeloma (≥30% plasma cells in a bone marrow biopsy specimen or lytic bone
lesions)

3. Cytotoxic chemo or radiation therapy ≤4 weeks of study entry or following baseline
evaluation

4. Symptomatic cardiac arrhythmias or O2-dependent restrictive cardiomyopathy

5. Dialysis-dependent

6. Untreated or uncontrolled infections.

7. Serious medical conditions, laboratory abnormality, or psychiatric illness that would
prevent the subject from signing the informed consent form.

8. Pregnant or breast feeding females (lactating females must agree not to breast feed
while taking pomalidomide).

9. Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study.

10. Use of any other experimental drug or therapy within 28 days of baseline.

11. Known intolerance to steroids.

12. Known hypersensitivity to thalidomide or lenalidomide

13. The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs.

14. Concurrent use of other anti-cancer agents or treatments.

15. Known HIV positivity is not an exclusion, unless cluster of differentiation 4 (CD4)
counts <200/microliter and/or patient has multi-drug resistant HIV infections and/or
other concurrent AIDS-defining conditions. HIV b-DNA < 75 copies/mL.