Inclusion Criteria:

• Subject has provided informed consent.
• Patients who have been previously treated with 3 or more lines of therapy, i.e. proteasome inhibitors, immuno-modulatory agents such as lenalidomide and monoclonal antibodies such as daratumumab, and have progressed within past 6 months. Participants with previous failed autologous transplant and progressed within 6 months after autologous transplant. Note: induction with or without hematopoietic stem cell transplant and with or without maintenance therapy is considered a single regimen.
• Subjects must have measurable disease (as determined by the central lab), including at least one of the criteria below:
  • M-protein quantities ≥ 0.5 g/dl by SPEP or
  • ≥ 200 mg/24 hour urine collection by UPEP or
  • serum free light chain levels > 100 mg/L (milligrams/liter involved light chain) and an abnormal kappa/lambda (κ/λ) ratio in patients without detectable serum or urine m-protein or
  • For patients with immunoglobulin class A (IgA) myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement, a serum IgA level ≥ 500 mg/dL.

Non-secretory participants are eligible provided the participant has > 20% bone marrow plasmacytosis OR multiple (≥3) plasmacytomas or lesions on MRI at the time of diagnosis or study enrollment, OR the presence of lesions (≥ 3) on PET/CT scan.

• Adequate organ function:

  • Absolute neutrophil count (ANC) ≥ 1.0 x 109/L without growth factor support for 7 days (14 days if pegfilgastrim) . Platelets (plt) ≥ 50 x 109/L without transfusion for 7 days. However, patient can be enrolled if the ANC and platelets are low due to disease
  • Potassium within normal limits or correctable with supplements
  • Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 2.5 x upper limit of normal (ULN)
  • Serum bilirubin ≤ 1.5 x ULN
  • Estimated serum creatinine clearance of ≥ 45 mL/min using the Cockcroft-Gault equation or directly calculated from the 24-hour urine collection method or ≥30 mL allowed if renal insufficiency is attributed to myeloma.
  • International normalized ratio (INR) < 1.5 x ULN and partial thromboplastin time (PTT) < 1.5 x ULN
  • Ejection fraction by ECHO or MUGA of ≥ 40% performed.
  • Participants must have adequate pulmonary function studies (PFTs), > 50% of predicted on mechanical aspects (FEV1, FVC) and diffusion capacity ( DLCO) > 50% of predicted (adjusted for hemoglobin). If the participant is unable to complete PFTs due to disease-related pain or other circumstances that make it difficult to reliably perform PFTs, documentation of pulmonary function adequate for transplant will occur via a CT scan without evidence of major pulmonary disease, and arterial blood gas results.
• Participants must have a performance status of 0-2 based on ECOG criteria. Participants with poor performance status (3-4) based solely on bone pain will be eligible, provided there is documentation to verify this.
• Negative serum or urine pregnancy test (sensitivity of at least 25 mIU/mL) at screening.

Exclusion Criteria:

• Prior allogeneic transplant.
• Known hypersensitivity or allergy to ascorbic acid or melphalan.
• Participants must not have a concurrent malignancy unless it can be adequately treated by non-chemotherapeutic intervention. Participants may have a history of prior malignancy, provided that he/she has not had any chemotherapy within 365 days of study entry AND that life expectancy exceeds 5 years at the time of study entry.
• Participants must not have life-threatening comorbidities.
• History or evidence of myeloma associated with immunodeficiency states (e.g.: Hereditary immune deficiency, HIV, organ transplant or leukemia).
• Known human immunodeficiency virus (HIV) disease (requires negative test for clinically suspected HIV infection).
• Evidence of CNS myeloma.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, recent (within 6 months) myocardial infarction, uncontrolled or symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, uncontrolled hypertension on appropriate therapy or psychiatric illness/social situations that would limit compliance with study requirements.
• Concurrent use of Coumadin (warfarin)
• Patients with G6PD deficiency
• Patients with a history of oxalate renal stones or a known history of multiple renal stones
• Diabetic patients who rely on a glucometer to dose insulin as ascorbate can interfere with glucometer readings