This study includes extended CD34+ profiling on the apheresis product of multiple myeloma patients undergoing standard-of-care quad-induction followed by motixafortide + G-CSF mobilization, and in addition, assesses the pharmacodynamics (PD) of motixafortide following "standard" (~12 hours) vs "early" (~16 hours) dosing. The investigators hypothesize that quad-induction may alter the stem cell subsets within the mobilized graft. The investigators further hypothesize that standard and early dosing strategies will result in comparable mobilization and stem cell collection rates.

Inclusion Criteria:

• Subjects must be between the ages of 18 and 78 years, inclusive.

• Histologically confirmed multiple myeloma expected to receive high-dose chemotherapy (HDT) and autologous stem cell transplantation (ASCT)

• Received ≥3 cycles but ≤6 cycles of daratumumab-based quadruplet induction therapy (quadruplet induction therapy: combining daratumumab, a proteasome inhibitor, an IMiD, and dexamethasone) before ASCT

• At least one week (7 days) from last induction cycle prior to the first dose of G-CSF for mobilization

• The subjects should be in first or second CR (including CR and SCR) or PR (including PR and VGPR)

• ECOG performance status 0 or 1

• Adequate organ function at screening as defined below:

  • White blood cell (WBC) counts > 2.5 × 10^9/L
  • Absolute neutrophil count > 1.5 K/cumm
  • Platelet count >100 K/cumm
  • GFR value of ≥15 mL/min/1.732 (by MDRD equation)
  • ALT and/or AST ≤2.5 × ULN
  • Total bilirubin ≤2.0 × ULN unless the participant has Gilbert disease
  • INR or PT: ≤1.5 × ULN unless participant is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants
  • aPTT: ≤1.5 × ULN unless participant is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants.

• Female subjects must be of non-childbearing potential or, if of childbearing potential, must have a negative serum pregnancy test at screening and negative urine or serum pregnancy test within 7 days prior to G-CSF first administration.

Non-childbearing potential is defined as (by other than medical reasons):

• ≥45 years of age and has not had menses for over 2 years

• Post hysterectomy, bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation at least 6 weeks prior to screening

  • Women of childbearing potential must agree to use 2 methods of effective contraception: One barrier method (e.g., diaphragm, or condom or sponge, each of which are to be combined with a spermicide) and one hormonal method, unless she uses a highly effective method. Highly effective methods of contraception include:

• Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, transdermal

• Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, implantable, intrauterine device (IUD)

• Intrauterine hormone-releasing system (IUS)

• Bilateral tubal occlusion

• Vasectomized partner

• Sexual abstinence These methods must be used starting at study enrollment and for the duration of study participation through 8 days after the last dose of motixafortide.

Male subjects must agree to use an adequate method of contraception (barrier method) starting with the first day of G-CSF administration through 8 days after the last dose of motixafortide.

• Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion Criteria:

• Previous history of autologous or allogeneic-HCT

• Failed previous HSC collections or collection attempts

• Taken any of the listed below concomitant medications, growth factors or stimulating agents within the designated washout period:

  • Dexamethasone: 7 days
  • Thalidomide: 7 days
  • Lenalidomide: 7 days
  • Pomalidomide: 7 days
  • Bortezomib: 7 days
  • Carfilzomib: 7 days
  • Ixazomib: 7 days
  • G-CSF: 14 days
  • GM-CSF or pegfilgrastim: 21 days
  • Erythropoietin or erythrocyte-stimulating agents: 30 days
  • Eltrombopag, romiplostim or platelet-stimulating agents: 30 days
  • Carmustine (BCNU): 42 days/6 weeks

• Received >6 cycles lifetime exposure to an IMiD

• Received >8 cycles of alkylating agent combinations

• Received >6 cycles of melphalan

• Received prior treatment with radioimmunotherapy (e.g., radionuclides, holmium)

• Received prior treatment with venetoclax

• Has received a live vaccine within 30 days of the planned start of G-CSF administration. Seasonal flu vaccines that do not contain live virus are permitted.

• Known active CNS metastases or carcinomatous meningitis

• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to motixafortide, G-CSF or other agents used in the study

• Has an active or uncontrolled infection requiring systemic therapy

• Has a known additional malignancy that is progressing or requires active treatment

• Has a known underlying medical condition that, in the opinion of the treating physician or Principal Investigator, would preclude study participation.

• Is currently participating in an investigational treatment study, or has participated in a study of an investigational agent and received study therapy, or has been treated with an investigational device, within 4 weeks prior to the first dose of treatment.

• O2 saturation < 92% (on room air)

• Personal history or family history of long QT syndrome or torsade de pointes

• History of unexplained syncope, syncope from an uncorrected cardiac etiology, or family history of sudden cardiac death.

• History of myocardial infarction, CABG, coronary or cerebral artery stenting and/or angioplasty, stroke, cardiac surgery, or hospitalization for congestive heart failure within 3 months prior to study enrollment, Angina Pectoris Class >2 or NYHA Heart Failure Class >2.

• ECG at screening showing QTcF >470 msec and/or PR >280 msec

• Mobitz II 2nd degree AV Block, 2:1 AV Block, High Grade AV Block, or Complete Heart Block, unless the participant has an implanted pacemaker or implantable cardiac defibrillator (ICD) with backup pacing capabilities.

• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial, in the opinion of the treating physician or Principal Investigator.

• Is pregnant or breast-feeding or expecting to conceive or women of childbearing potential unless consent to use two contraceptive methods or highly effective contraception as detailed above, within the projected duration of the trial, starting with the Screening Visit through 8 days after the last dose of study drug.

• HIV-infected if not on effective anti-retroviral therapy with undetectable viral load for 6 months. Patients with HIV who are receiving effective anti-retroviral therapy and have had an undetectable viral load for at least 6 months are eligible.

• Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible.

• History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible.