Safety Study of a Chemokine Receptor (CXCR4) Antagonist in Multiple Myeloma Patients
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      BKT-140 drug substance is a highly selective chemokine receptor (CXCR4) antagonist, which is
      developed by Biokine as a novel therapy for Multiple Myeloma (MM, a type of blood cancer).
      The unique combination of activities of BKT140, i.e., the induction of the exit of blood
      cells such as stem cells and mature cells from the bone marrow to the peripheral blood,
      coupled with specific induction of MM cell death by BKT-140, represents a novel therapeutic
      strategy against MM.
    

Detailed description: 
      The chemokine CXCL12 (also called SDF-1 - stromal-derived-factor-1) and its receptor, CXCR4
      ((CXC Chemokine Receptor 4), a molecule endowed with potent chemotactic activity for
      hematopoietic cells, together play a pivotal role in the trafficking of hematopoietic stem
      cells to the bone marrow 10,11. The CXCL12/CXCR4 axis is also critically involved in the
      retention of hematopoietic cells within the BM microenvironment. Following chemotherapy and
      irradiation, the CXCL12/CXCR4 axis delays the recovery of the BM progenitor cells and the
      exit of mature cells such as neutrophils and monocytes to the periphery. Consequently,
      disruption of the CXCL12/CXCR4 interaction results in mobilization of hematopoietic cells
      including stem cells and a faster recovery of the treated BM.

      BKT140 (4F-benzoyl-TN14003) is a highly selective and unique CXCR4 antagonist. Pre-clinical
      studies showed that BKT140 binds CXCR4 with high affinity (1nM) 13. Biokine has demonstrated
      the ability of the CXCR4 antagonist, BKT140, to mobilize various WBC such as neutrophils and
      monocytes as well as progenitor and stem cells, from the BM. The ability of BKT140 to
      stimulate the mobilization of these cells is superior to that of AMD3100, a CXCR4 antagonist
      that is in clinical development for mobilization of stem cells in MM and lymphoma patients,
      both qualitatively and quantitatively. BKT140 synergizes much more efficiently with G-CSF
      when compared to AMD3100. Moreover, Biokine has shown that BKT140, in synergism with G-CSF
      (NEUPOGEN®), is much more efficient in increasing the numbers of neutrophils and activated
      monocytes in the blood, by several folds as compared to G-CSF alone. BKT140 also shortens the
      neutropenic period due to an early release of neutrophils and monocytes from the BM. More
      importantly, BKT140, in synergism with G-CSF, reduces the anemic period caused by
      chemotherapy, due to a RBC production, which does not occur when G-CSF is given as a sole
      treatment. More importantly, BKT140, but not G-CSF or AMD3100, is also capable of shortening
      the period of cytopenia by boosting both the recovery of all hematopoietic cells in the BM
      and their exit to the periphery, and therefore shortening the period of cytopenia following
      chemotherapy or irradiation and BM transplantation. Importantly, Biokine has shown that upon
      interaction with CXCR4, BKT140, but not AMD3100, selectively, specifically and rapidly
      stimulates human leukemia and myeloma cell death in vitro and in vivo. Furthermore, BKT140
      synergizes with other chemotherapeutic agents such as rapamycine to induce MM cell death.
    

Intervention name(s): BKT140
Intervention type(s): Drug
Intervention description(s): BKT-140 drug substance is a highly selective CXCR4 antagonist. BKT140 will be injected S.C once at dose of 0.03, 0.1, 0.3, 0.9 mg/kg
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Multiple Myeloma; CXCR4; Stem Cells; Mobilization; Transplantation; Chemotherapy