Uproleselan (GMI-1271) for GI Toxicity Prophylaxis During Melphalan-Conditioned Autologous Hematopoietic Cell Transplantation (Auto-HCT) for Multiple Myeloma (MM)
Condition: Multiple Myeloma
MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell
Intervention: Uproleselan; Placebo; Melphalan
Intervention description: Provided by study; Provided by study; -Standard of care
Intervention MeSH terms: Melphalan
Phase: Phase 2
Study type: Interventional
Primary purpose: Supportive Care
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 51.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The investigators hypothesize that prophylactic E-selectin inhibition via administration of
      uproleselan during melphalan conditioning will reduce the gastrointestinal (GI) toxicity in
      multiple myeloma (MM) patients undergoing auto-transplant, as assessed via diarrhea severity
      scoring per CTCAE v5.0, while potentially increasing chemosensitivity of malignant MM cells
      to high-dose melphalan.
    

Eligibility criteria:

        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.