A Phase II Trial of Anti-KIR in Smoldering Multiple Myeloma

• INCLUSION CRITERIA:

• Diagnosis of SMM will be made in accordance with the clinical diagnostic criteria set forth by the International Myeloma Working Group. These criteria include:

  • Serum M-protein greater than or equal to 3 g/dl and/or bone marrow plasma cells greater than or equal to 10 percent
  • Absence of anemia: Hemoglobin greater than or equal to 10 g/dl
  • Absence of renal failure: calculated creatinine clearance (according to MDRD) greater than or equal to 40 ml/min (or alternatively based on standard creatinine level criteria of 2 mg/dl)
• Absence of hypercalcemia: Calcium less than or equal to 10.5 mg/dl
• Absence of lytic bone lesion (skeletal survey)
• The diagnoses will be confirmed by serum/urine protein electrophoresis, immunofixation and light-chain assays; as well as immunohistochemical analyses of the bone marrow biopsy.
• Age greater than or equal to 18 years.
• ECOG performance status of 0-1.
• Male or female patient who accepts and is able to use recognized effective contraception (oral contraceptives, IUCD, barrier method of contraception in conjunction with spermicidal jelly) through the study and for four months following the final dose of study drug when relevant.
• The patient must be competent to sign an informed consent form.

EXCLUSION CRITERIA:

• Patients with a diagnosis of MM or a clinical suspicion of an ongoing progression into full-blown MM
• Patients without measurable disease defined as serum M-protein less than 1 g/dL.
• Previous treatment having a proven or potential impact on myeloma cell proliferation or survival (including conventional chemotherapies, immunomodulatory drugs (IMiDs), or proteasome inhibitors).
• Use of any investigational agent within the last 3 months.

• Clinical laboratory values at screening:

  • Platelet levels less than 75 times 10(9)/L
  • ANC levels less than 1 times 10(9)/L
  • Bilirubin levels greater than 1.5 ULN ; ALT and AST greater than 3.0 ULN (grade 1 NCI)
• Primary or associated amyloidosis

• Known abnormal cardiac status with any of the following:

  • NYHA stage III or IV congestive heart failure
  • Myocardial infarction within the previous 6 months
  • Symptomatic and/or treatment-refractory cardiac arrhythmia. Patients with controlled or asymptomatic arrhythmia are not excluded from this study.

• Current active infectious disease or positive serology for:

  • Human Immunodeficiency Virus (HIV)
  • Hepatitis C Virus (HCV)
  • Hepatitis B Surface Antigen

• Severe type of autoimmune disease defined as:

  • One which currently requires or previously required long-term systemic immunosuppressive or immunomodulatory therapy (including corticosteroids, administered by systemic route)
  • And/or it has a substantial probability to cause an irreversible injury to any tissue (e.g. Hashimoto thyroiditis).
  • And/or it is recent or unstable, or has a substantial risk to progress and cause severe complications (e.g. Graves disease)
  • Enrollment of other non severe types of auto-immunes disease requiring topical therapy, or NSAIDS can be considered on a case by case basis by the Principal Investigator.
• History of a lymphoproliferative malignancy.
• History of other malignancy (apart from basal cell carcinoma of the skin or in situ cervical carcinoma) except if the patient has been free of symptoms and without active therapy during at least the previous 5 years.
• Serious concurrent uncontrolled medical disorder.
• History of allograft or solid organ transplantation.
• Any psychological or familial condition potentially interfering with compliance with the study protocol and follow-up schedule.
• Pregnant or lactating women.