Uproleselan (GMI-1271) for GI Toxicity Prophylaxis During Melphalan-Conditioned Autologous Hematopoietic Cell Transplantation (Auto-HCT) for Multiple Myeloma (MM)

Inclusion Criteria:

* Biopsy-confirmed multiple myeloma (MM) (per IMWG criteria).
* Undergoing first auto-HCT for MM in first partial response (PR) or better
* Conditioning regimen to be single agent melphalan (200 mg/m\^2)
* Adults 18 to 75 years of age, inclusive
* ECOG performance status ≤ 2
* Mobilized ≥ 5.0 x 10\^6 CD34+ cells/kg (i.e. sufficient CD34+ HSCs for one auto-HCT, with at least one back-up graft in reserve)
* Adequate bone marrow and organ function prior to stem cell mobilization as defined below:

  * Leukocytes, absolute neutrophil count, and platelets within institutional standard limits for high-dose melphalan autologous stem cell transplant
  * Total bilirubin ≤ 1.5 x ULN (unless the patient has a history of Gilbert's Syndrome, in which case, total bilirubin must be ≤ 2.5 times the ULN)
  * AST(SGOT)/ALT(SGPT) ≤ 3.0 x ULN
  * Creatinine clearance ≥ 30 mL/min by Cockcroft-Gault
  * Baseline pulmonary function test (PFT) with carbon monoxide diffusion capacity in the lung (DLCO) ≥ 50% and forced expiratory volume in 1 second (FEV1) both within institutional standard limits for high-dose melphalan autologous stem cell transplant
* The effects of uproleselan (GMI-1271) on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, prior sterilization procedure, abstinence, etc.) prior to study entry, for the duration of study participation and for 12 weeks after the completion of the study. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. Should a man who is participating in the study become aware that he has impregnated a partner, he must inform his treating physician immediately.
* Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

* A history of other malignancy with the exception of malignancies for which all treatment was completed at least 2 years before registration and the patient has no evidence of disease.
* Active signs or symptoms of CNS involvement by malignancy (lumbar puncture not required). Prior history of CNS involvement is acceptable, if patient has completed treatment for CNS involvement with documented treatment response.
* Prior exposure to uproleselan (GMI-1271)
* Currently receiving any other investigational agents
* A history of allergic reactions attributed to compounds of similar chemical or biologic composition to uproleselan or melphalan
* Known active infection with hepatitis A, B (e.g., HBsAg positive), or C (e.g., anti-HCV positive), or human immunodeficiency virus
* Uncontrolled acute life-threatening bacterial, viral, or fungal infection-Myocardial infarction within 6 months of uproleselan/placebo dosing, or subject has current significant cardiovascular disease, such as uncontrolled or symptomatic arrhythmias, congestive heart failure, hemodynamic instability, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
* Any medical, psychiatric, or other condition which, in the opinion of the investigator, unfavorably alters the risk-benefit of subject participation, is likely to interfere with trial completion, assessments, or interpretation of trial results, or otherwise would make the subject an inappropriate subject for this trial.
* Pregnant and/or breastfeeding.
* Women of childbearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception during the trial and for 12 weeks following the last dose of uproleselan/placebo. Women who are postmenopausal with amenorrhea for at least 1 year prior to trial entry and follicle stimulating hormone (FSH) serum levels consistent with postmenopausal status (\>28U/L) will be considered NOT of childbearing potential. Highly effective contraception includes:

  * Total abstinence with a male partner.
  * Female sterilization (has had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least 6 weeks before uproleselan/placebo. In case of oophorectomy alone, the subject would be eligible only when the reproductive status of the woman has been confirmed by follow up hormone level assessment.
  * Male sterilization (at least 6 months prior to Screening). For female subjects on the trial, the vasectomized male partner should be the sole partner for that subject.
  * BOTH of the following forms of contraception consistently used together:

    * Injected, transdermal, or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \<1%) with the exception of intrauterine devices, which are excluded due to the risk of infection and bleeding.
    * Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with or without spermicidal foam/gel/film/cream/vaginal suppository.
    * Men who are sexually active and not willing to use condoms during the trial and for 12 weeks following the last dose of uproleselan/placebo, unless they have undergone vasectomy for sterilization (at least 6 months prior to Screening), are excluded from trial participation.
* Men who are sexually active and not willing to use condoms during the trial and for 12 weeks following the last dose of uproleselan/placebo, unless they have undergone vasectomy for sterilization (at least 6 months prior to Screening), are excluded from trial participation.