QUILT-3.005: A Study of ALT-803 in Patients With Relapsed or Refractory Multiple Myeloma

The purpose of this study is to evaluate the safety, determine the Maximum Tolerated Dose
(MTD) or the Minimum Efficacious Dose (MED) and characterize the immunogenicity and
pharmacokinetic profile of ALT-803 in treated patients. The effect of ALT-803 on the
peripheral absolute lymphocyte counts and white blood cell counts, the number and phenotype
of peripheral blood T (total and subsets) and NK cells will be evaluated. The anti-tumor
responses of ALT-803 will also be assessed in this trial.

ENTRY CRITERIA:

DISEASE CHARACTERISTICS:

- Confirmed diagnosis of relapsed/refractory multiple myeloma after treatment with at
least two different previous regimens.

- Refractory disease is defined as progressive disease while on therapy or
progression within 60 days of therapy.

- Progressive disease is defined by a 25% increase from the lowest response value
in specified tests.

- Measurable disease as defined by at least one of the following:

- Serum M-protein ≥ 1g/dL (for IgG, IgM) or 0.5 g/dL (for IgA)

- Urine M-protein ≥ 200mg/24hours

- Serum free light chains ≥ 10 mg/dL and abnormal kappa/lambda ratio

PRIOR/CONCURRENT THERAPY:

- No anti-myeloma treatments within 14 days before the start of study treatment.

- Must have recovered from side effects of prior treatments.

PATIENT CHARACTERISTICS:

Performance Status

• ECOG 0, 1, or 2

Bone Marrow Reserve

- Absolute neutrophil count (AGC/ANC) ≥ 1000/uL

- Platelets ≥ 30,000/uL

- Hemoglobin ≥ 8g/dL

- Absolute lymphocytes ≥ 800/uL

- Leukocytes ≥ 3,000/uL

Renal Function

• Glomerular Filtration Rate (GFR) > 40mL/min or Serum creatinine ≤ 1.5 X ULN

Hepatic Function

- Total bilirubin ≤ 2.0 X ULN

- AST, ALT, ALP ≤ 3.0 X ULN, or ≤ 5.0 X ULN (if liver metastases exist)

- No positive Hep C serology or active Hep B infection

Cardiovascular

- No congestive heart failure < 6 months

- No unstable angina pectoris < 6 months

- No myocardial infarction < 6 months

- No history of ventricular arrhythmias

- No history of supraventricular arrhythmias

- No NYHA Class > II CHF

- No marked baseline prolongation of QT/QTc interval

Pulmonary

• Normal clinical assessment of pulmonary function

Other

- Negative serum pregnancy test if female and of childbearing potential

- Women who are not pregnant or nursing

- Subjects, both females and males, with reproductive potential must agree to use
effective contraceptive measures for the duration of the study

- No known autoimmune disease other than corrected hypothyroidism

- No known prior organ allograft or allogeneic transplantation

- Not HIV positive

- No history or evidence of uncontrollable CNS disease

- No psychiatric illness/social situation

- No other illness that in the opinion of the investigator would exclude the subject
from participating in the study

- Must provide informed consent and HIPPA authorization and agree to comply with all
protocol-specified procedures and follow-up evaluations

- No active systemic infection requiring parenteral antibiotic therapy

- No on-going chronic systemic corticosteroid (>10 mg daily prednisone equivalent) use
or other immunosuppressive therapy (a history of mild asthma not requiring therapy is
eligible). Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg
daily prednisone equivalent, are permitted in the absence of active autoimmune
disease.