Background: TG-0054 (burixafor) is a potent and selective antagonist of human chemokine receptor CXCR4 that inhibits the binding of stromal-derived factor 1 (SDF-1). Interruption of the CXCR4/SDF-1 interaction prevents sequestration of CD34+ stem cells to the bone marrow and subsequently mobilizes these cells into the peripheral blood within 1 to 3 hours of drug administration. Materials and Methods: An open-label, phase II pilot trial was conducted in patients with multiple myeloma (MM), non-Hodgkin's lymphoma (NHL), or Hodgkin's lymphoma (HL) to evaluate the safety and stem cell mobilization of TG-0054 in combination with G-CSF. We planned to treat twelve patients with subcutaneous injections of 10 µg/kg/day G-CSF in the afternoon for 4 days. On the morning of Day 5, patients received 3.14 mg/kg TG-0054 and underwent large volume (18-24L) leukapheresis approximately 2 hours post-drug infusion. Patients were allowed by protocol to undergo leukapheresis for 1-5 days to obtain the predetermined target of ≥5.0 x 106 CD34+ cells/kg. 9 of 12 patients have been treated thus far with a plan to treat 3 additional patients. Results: A planned interim analysis revealed that6 of the 9 patients treated thus far collected more than 10 x 106 CD34+ cells/kg in 1 leukapheresis session. 2 patients required 2 days to achieve the study endpoint, and 1 outlier patient who had received Revlimid only 1 week prior to peripheral blood CD34 analysis failed to mobilize stem cells until he was allowed 2 more weeks to recover from his Revlimid treatment. Burixafor was well tolerated, and there were no adverse events that were attributed to the drug. All of the patients engrafted promptly after melphalan (7 patients) or BEAM (2 patients) conditioning regimens. Conclusion: Burixafor in combination with G-CSF is a potent and well-tolerated mobilizer of stem cells into the peripheral blood, and with the exception of 1 outlier, was able to mobilize >5.0 x 106 CD34+ cells/kg in 1-2 leukapheresis sessions in all patients treated thus far (median 1 day). This contrasts with our historical controls that required a median of 2-3 days to achieve a collection of ≥5.0 x 106 CD34+ cells/kg. A total of 12 patients will be treated on this pilot study. These encouraging results warrant the further testing of this drug in a larger randomized clinical trial. Disclosures Hsu: Taigen Biotechnology: Employment. Chang:Taigen Biotechnology: Employment. Schuster:Taigen Biotechnology: Research Funding.

Velafermin was well tolerated by autologous PBSCT patients at doses up to 0.2 mg/kg.

Background TG-0054 (burixafor) is a potent and specific antagonist of the human CXCR4 chemokine receptor. TG-0054 blocks the interaction between CXCR4 and stromal cell-derived factor-1 (SDF-1), thus causing a rapid mobilization of stem cells from the bone marrow into peripheral blood within 1-3 hours of intravenous administration of the drug. Materials and Methods: An early phase II trial was conducted in patients with multiple myeloma (MM), non-Hodgkin lymphoma (NHL) or Hodgkin disease (HD) to evaluate the safety and stem cell mobilization of TG-0054 alone or in combination with G-CSF. 12 patients (1 HL, 7 MM, and 4 NHL patients) received an i.v. dose of 3.14 mg/kg TG-0054, and peripheral blood CD34 counts were assessed at 2, 4 and 6 hours post drug infusion. Patients who achieved at least 10 CD34 cell/ul in the peripheral blood were collected by large volume leukapheresis (24L) for 1-4 days to obtain a predetermined target of >2.5 x 106 CD34 cells /kg. Results: Seven patients (1 HD, 6 MM) were successfully mobilized with TG-0054 as a single agent achieving a cumulative CD34+ stem cell collection of 4.0 to 10.4 x106 cells /kg over 2-4 leukapheresis sessions. Patients who failed to mobilize with TG0054 as a single agent on day +1 were placed on the second arm of the study, where they received 5 doses of granulocyte colony stimulating factor (G-CSF) at a dose of 10 ug/kg beginning on day +4 with TG-0054added back in combination on day +8. These remaining five patients (1 MM, 4 NHL) who did not mobilize with TG0054 alone on day +1 and received G-CSF plus TG-0054 were leukapheresed on day +8. Those patients achieved a cumulative CD34 peripheral blood stem cell collection of of 3.2-21.0 x106 cells /kg over 1-4 leukaphereses sessions. Conclusion: TG-0054 exhibited potent and rapid mobilization of CD34+ stem cells, with favorable safety profile in patients. Engraftment All 12 patients received conditioning regimens (BEAM for the lymphoma patients and melphalan for the myeloma patients) followed by a stem cell infusion of at least 3.0 x106 CD34+ cells/kg. All patients engrafted without delay compared to historical controls. Median days to WBC engraftment were 12. Median days to platelet recovery of 20,000 and 50,000 were 20 and 20.5 days, respectively. Engraftment results of TG-0054 mobilized patients are similar to those seen in a matched group of historical controls. We have observed that mobilization with TG-0054 caused a preferential mobilization of mononuclear cells (MNC) component of the graft. Percent MNC in TG-0054 mobilized patients‘ grafts were 78.9+15.2 (median 81.5) as compared to percent of MNC in G-CSF mobilized patients‘ grafts of 62.6+27.7 (median 69.6). Disclosures: Schuster: TaiGen Biotechnology Co., Ltd: Research Funding. Tsai:TaiGen Biotechnology Co., Ltd: Employment. Hsu:TaiGen Biotechnology Co., Ltd: Employment, Equity Ownership. Chang:TaiGen Biotechnology Co., Ltd: Employment. Hsu:TaiGen Biotechnology Co., Ltd: Employment.

We report a case of a 72 year old female who was referred to our institution in August 2010 for Myelodysplastic syndrome (MDS) with a deletion of part of the long arm of chromosome 5 [i.e., del(5) (q12q33)]. In June 2014, she transformed to Chronic Myelogenous Leukemia (CML), where cytogenetic and FISH analysis of the bone marrow (BM) revealed the del(5q) in 1.5% of nuclei and a complex BCR/ABL1 translocation [i.e., 45,XX,t(9;15;22)(q34;p10;q11.2),-22]. Six weeks later, in July 2014, she transformed to an Acute Myelogenous Leukemia (AML) blast crisis. RT-PCR was positive for BCR/ABL1 transcript. The patient was treated with a tyrosine kinase inhibitor, Nilotinib, then had a haploidentical allogeneic bone marrow transplant from her son, and was in remission after treatment. However, throughout the course of nine subsequent cytogenetic analyses, the patient continued to undergo clonal chromosome evolution, even during remission. Transformation from MDS del(5q) to CML with rapid progression to blast crisis has rarely been reported. To our knowledge, transformation with this complex translocation has never been described. Here we describe these rare cytogenetic findings and discuss possible mechanisms involved in the persistent and evolving clonal cytogenetic abnormalities seen during the clinical course of the disease.

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Mucositis is a painful side effect of many transplant conditioning regimens used in HDC and PBSCT. This complication often requires treatment with potent narcotic analgesics and may even require intravenous patient-controlled analgesia (PCA) for adequate pain relief as well as total parenteral nutrition (TPN). Infections in this setting may also result from disruption of the mucosal barrier with subsequent migration of intestinal bacteria into the blood stream. Previous treatments with oral rinses and topical applications of soothing gels have largely been ineffective. Recently, a breakthrough class of drugs in the fibroblast growth factor (FGF) family holds great promise in more effectively ameliorating or even preventing oral mucositis (OM). We report on the results of a Phase I trial with CG53135-05, a novel investigational protein therapeutic (FGF-20) that promotes epithelial and mesenchymal cell proliferation in vitro and has demonstrated activity in animal models. 14 patients (ages 25–75) undergoing HDCT with PBSCT were treated with escalating doses of study drug, including 0.1 mg/kg, 0.2 mg/kg and 0.33 mg/kg (concentrations are determined by the UV method which are equivalent to 0.3, 0.6, and 1 mg/kg by the Bradford method previously used). Conditioning regimens used included melphalan (Mel 200), cyclophosphamide, carmustine and etoposide (CBV), carboplatin and thiotepa (CT), cyclophosphamide, etoposide and carmustine (CEC) and busulfan/cyclophosphamide (targeted BuCy). The primary objective of this phase I trial was to evaluate safety, tolerability and pharmacokinetics of CG53135-05. Patients (pts.) were also scored daily for presence of OM using both the WHO and OMAS (oral mucositis assessment scale) grading scales. 7/14 pts. in this study experienced no OM (including 2 Mel 200 patients), 5 pts. experienced only grade 1 OM. while 2 pts. (both treated with Mel 200) experienced grade 3 OM, and no pts. experienced grade 4 OM. 1 pt. experiencing grade 3 OM required TPN. Only 4 pts. experienced diarrhea that lasted more than 4 days and only 1 pt. had gut mucositis-associated (E. coli) bacteremia. The median day of engraftment (ANC>500/uL) occurred on day 14 (range: day 11–19). Patients tolerated the study drug well with no significant side effects up to a dose of 0.33 mg/kg. At that dose, 2 pts. experienced an infusional reaction consisting of fevers, nausea, and mild hypotension. Pharmacokinetics were measured at all dose levels and will be presented. CG53135-05 is a member of a breakthtrough drug class (FGF family) that was well tolerated in autologous stem cell transplant patients at doses up to 0.33 mg/kg with apparent clinical effects in ameliorating or preventing OM - 12/14 pts, thus, avoided severe (grades 3–4) mucositis following HDCT. A larger Phase II clinical trial is planned.