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

This is a Phase I/II, open-label, multi-center, competitive enrollment and dose escalation study of N-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 N-803 in treated patients. The effect of N-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 N-803 will also be assessed in this trial.

Eligibility Criteria:
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.