An Open-label, Dose-escalation Safety and Tolerability Trial Assessing Anti-KIR (1-7F9) in Subjects With Multiple Myeloma
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Anti-KIR (1-7F9)
Intervention description: human monoclonal antibody
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: multiple myeloma; Anti-KIR (1-7F9)

Summary:

      Development of new treatments for diseases such as multiple myeloma is a focus for research.
      The research being conducted is on treatment called Anti-KIR (1-7F9), which activates the
      body's own cells to kill tumor cells. This is different from many other treatments where
      chemicals are given to kill tumor cells. The purpose of the study is to determine a safe dose
      of Anti-KIR (1-7F9) to administer in humans and to gain information about its effectiveness
      in the treatment of multiple myeloma.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Informed consent obtained before any trial-related activities. (Trial-related
             activities are any procedure that would not have been performed during normal
             management of the subject.)

          2. Bone marrow plasmacytosis > 10% (as determined by bone marrow aspirate) or
             plasmacytoma

          3. Relapse or progression after at least one prior systemic treatment regimen for
             Multiple Myeloma (MM) as evidenced by ≥ 25% increase in the M-protein as compared to
             the best response from the previous treatment regimen.

        3a. One prior therapy for multiple myeloma, Measurable disease, as defined by persistent
        presence of serum and/or urine monoclonal protein or abnormal serum free light chain ratio
        following the prior treatment.

        a. Only for the last seven patients enrolled into the cohort 7 or Maximal Tolerated Dose
        (MTD).

        4. Full recovery from acute toxicities of prior anti-MM therapies. 5. Peripheral blood
        (Natural Killer) NK cells (Absolute CD16, 56)≥ 0.05 x 109/L (50/mm3) 6. Detectable binding
        of Anti-KIR (1-7F9) to subject NK cells 7. Age ≥ 18 years 8. Eastern Cooperative Oncology
        Group (ECOG) performance status of 0,1 or 2 9. Clinical laboratory values at screening:

          -  serum creatinine < grade 2 toxicity i.e. 1.5x upper limit of institutional normal
             value

          -  total bilirubin < 1.5x upper limit of institutional normal value

          -  Aspartate aminotransferase (AST) < or = 3x upper limit of institutional normal value

          -  Absolute Neutrophil Count (ANC) >1.2 x109/L

          -  Platelets >70x109/L

        Exclusion Criteria:

          1. Known or suspected allergy to trial product or related products

          2. Previous participation in this trial (dosed)

          3. Females of childbearing potential who are pregnant, breast-feeding or intend to become
             pregnant or are not using adequate contraceptive methods (appropriate methods include
             abstinence and the following methods: diaphragm, condom (by the partner), intrauterine
             device, sponge, spermicide or oral contraceptives)

          4. Male subjects who are sexually active and have not been surgically sterilized must be
             informed that they must either use a condom during intercourse, ensure that their
             partners practices contraception, or they must refrain from sexual intercourse during
             the study and until 1 month after completion of the trial.

          5. Use of an investigational agent within 30 days of the first dose of study drug (or
             five half-lives of any antibody).

          6. Current treatment with any other anti-MM therapy excluding prophylactic
             bisphosphonates.

          7. Radiotherapy against bone lesions within 4 weeks or visceral lesions within 8 weeks of
             Screening.

          8. Thalidomide or bortezomib treatment within 14 days of Screening.

          9. Cytotoxic chemotherapy (excluding thalidomide or bortezomib) or corticosteroid
             treatment within 28 days of Screening.

         10. Subjects with non-secretory multiple myeloma

         11. Subjects on dialysis

         12. Use of myeloid growth factor within 28 days of screening

         13. G-CSF treatment within 28 days of screening

         14. Active autoimmune disease

         15. Active infectious disease (e.g. HIV, chronic hepatitis, etc.) as judged by the
             investigator.

         16. New York Heart Association (NYHA) class III-IV heart failure

         17. Severe neurological / psychiatric disorder as judged by the investigator

         18. Clinical evidence of an active second malignancy, with the exception of basal cell
             carcinoma or in situ carcinoma of cervix.

         19. Subjects with a history of allogenic transplantation.

         20. Subject who have undergone autologous transplantation within the last 3 months.

         21. Mental incapacity or inadequate understanding of English.

         22. Any serious medical condition that in the opinion of the investigator, disqualifies
             the subject for inclusion in the trial.