Study to Investigate the Therapeutic Role of RNA Fragments in Platelet Production During Chemotherapy
Condition: Thrombocytopenia; Neoplasm; Cancer
MeSH terms: Thrombocytopenia
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to measure the therapeutic potential of Escherichia coli (E.
      coli) and yeast ribosomal Ribonucleic acid (RNA) fragments to maintain the production of
      platelets in patients undergoing cytotoxic therapy for cancer.
    

Detailed description: 
      Myelosuppressive chemotherapy has the potential to produce life threatening neutropenia,
      anemia, and thrombocytopenia. All of these conditions compromise therapeutic dosing which
      impacts survival as well as quality of life. The introduction of recombinant growth factors
      has enabled oncologists to minimize or prevent the development of treatment-induced anemia
      and neutropenia, but the management of chemotherapy-induced thrombocytopenia (CIT) remains a
      major challenge. American Society of Clinical Oncology (ASCO) guidelines recommend dose
      reduction in chemotherapy following onset of thrombocytopenia despite data showing full dose,
      on time, chemotherapy leads to reduced tumor burden and better overall survival [1-3].
      Patients with CIT experience potentially life threatening complications, delay in treatment,
      poorer outcomes, and consume inordinate amounts of health care resources for supportive care
      [4]. Development of an agent that ameliorates CIT would represent a major breakthrough in
      cancer treatment.

      Platelets are anuclear cell particles that are released into the bloodstream by
      megakaryocytes located in the bone marrow. The differentiation of megakaryocytes is regulated
      by an intricate interaction of specific cytokines and growth factors [5]. Bone marrow stromal
      elements are also critical to the differentiation and release of platelets. Cancer
      chemotherapy often depletes the stem and progenitor cells involved in platelet proliferation,
      which leads to a diminution of platelets and temporary interruption of platelet production
      lasting until stromal elements and megakaryocytes regenerate.

      There are several experimental agents targeted to prevent thrombocytopenia. These
      investigational agents are cytokines involved in the differentiation and production of
      platelets [6]. Currently, the only agent commercially available for prevention of
      thrombocytopenia is Neumega, a derivative of IL-11. Data on Neumega (Oprelekin) indicates a
      shorter duration of chemotherapy-induced thrombocytopenia, but the toxicity profile has
      prevented its widespread introduction into the clinical setting. Overall, the absence of
      agents that minimize or reverse CIT continues to severely limit many patients' ability to
      complete the full schedule of chemotherapy at the doses originally prescribed by treating
      oncologists [1].

      This study is a dose escalation trial investigating the anti-thrombocytopenic benefits and
      safety of single stranded RNA fragments. The short chain RNA fragments are obtained by
      controlled degradation of prokaryotic RNA with ribonuclease. Beljanski showed that these RNA
      fragments act as primers for DNA synthesis in vitro and found that variations in the method
      of degradation yielded different preparations that prime deoxyribonucleic acid (DNA)
      synthesis with distinct tissue specificity. The RNA fragments used in this study, when
      administered orally, localize in the bone marrow where they appear to prime DNA replication
      in stem cells resulting in proliferation of white blood cells and platelets. Beljanski et al.
      reported that these specific RNA fragments were effective in restoring normal levels of
      circulating platelets following drug induced thrombocytopenia [7;8]. Demonstrating the
      utility of these specific RNA fragments for prevention and treatment of thrombocytopenia
      among cancer patients undergoing chemotherapy is especially attractive given the absence of
      the side effects associated with growth factors and hormones.

      This trial investigated the efficacy of two RNA preparations-extracted, purified and
      fragmented according Beljanski's procedure-to ameliorate CIT: one derived from E. coli and
      the second from yeast (a eukaryote). RNA molecules are present in any diet and can be
      considered conditional essential nutrients under conditions of physiological stress [9].
      Purified RNA prepared by various methods can be found in nutritional products for
      hospitalized patients and infant formula [9-11]. This clinical trial evaluated the biologic
      effects of various doses of these specially prepared 'primer' RNA fragments on platelet
      numbers in cancer patients who have already developed thrombocytopenia while undergoing
      chemotherapy.
    

Intervention name(s): Realbuild
Intervention type(s): Dietary Supplement
Intervention description(s): Patient with chemotherapy induced thrombocytopenia takes RNA fragments orally to accelerate time to platelet recovery
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment