A Phase II Trial of Anti-KIR in Smoldering Multiple Myeloma
Condition: Multiple Myeloma; Myeloma; Smoldering Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Smoldering Multiple Myeloma
Intervention: (Anti-KIR)
Intervention description: Patients will receive anti-KIR(IPH2101) (1mg/kg) every other month for 6 cycles
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 9.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Monoclonal Antibody; NK Cell Mediated Killing; Response Rate; Pharmacokinetics; Biological Activity; Smoldering Multiple Myeloma; SMM

Summary:

      Background:

        -  Recent studies have shown that smoldering multiple myeloma has a high risk of
           progressing to multiple myeloma, an aggressive type of bone marrow cancer, within 5
           years of diagnosis. People with smoldering multiple myeloma have abnormal blood test
           results that show a high level of monoclonal protein (M-protein) in the blood and of
           plasma cells in the bone marrow. There are currently no known effective treatments to
           prevent smoldering multiple myeloma from developing into multiple myeloma, and there are
           no known tests for determining whether an individual with smoldering multiple myeloma
           will develop multiple myeloma.

        -  Certain cells in the immune system, known as natural killer (NK) cells, are active
           against multiple myeloma. The experimental drug anti-killer cell immunoglobulin-like
           receptor (anti-KIR) has been shown to help NK cells kill multiple myeloma cells.
           Researchers are interested in determining whether anti-KIR can be given to individuals
           with smoldering multiple myeloma to improve their abnormal blood test results.

      Objectives:

      - To evaluate the safety and effectiveness of anti-KIR as a treatment for abnormal blood test
      results related to smoldering multiple myeloma.

      Eligibility:

      - Individuals at least 18 years of age who have been diagnosed with smoldering multiple
      myeloma.

      Design:

        -  Participants will be screened with a physical examination and medical history, and will
           provide baseline blood, urine, and bone marrow samples before beginning the study drug.

        -  Participants will receive anti-KIR intravenously for 1 hour, and will be closely
           monitored for 24 hours after receiving the first dose. If there are no serious side
           effects, participants will receive five additional anti-KIR doses, one every other
           month, for a total of six treatment cycles.

        -  Participants will have monthly visits to provide additional blood and urine samples, and
           may have additional bone marrow biopsies as directed by the study researchers.

        -  Participants will have followup visits every 3 to 6 months for up to 5 years after
           receiving anti-KIR treatment.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Diagnosis of smoldering multiple myeloma (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
                  modification of diet in renal disease (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.

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

          -  Male or female patient who accepts and is able to use recognized effective
             contraception (oral contraceptives, intrauterine contraceptive device (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 multiple myeloma (MM) or a clinical suspicion of an
             ongoing progression into full-blown MM

          -  Patients without measurable disease defined as serum monoclonal protein (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

               -  Absolute neutrophil count (ANC) levels less than 1 times 10^9/L

               -  Bilirubin levels greater than 1.5 upper limit of normal (ULN) ; alanine
                  aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 3.0 ULN
                  (grade 1 National Cancer Institute (NCI))

          -  Primary or associated amyloidosis

          -  Known abnormal cardiac status with any of the following:

               -  New York Heart Association (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 non-steroidal inflammatory drugs (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.