High Dose Ascorbic Acid and Low Dose Melphalan in Treating Patients with Relapsed and Refractory Multiple Myeloma

Inclusion Criteria

• Subject has provided informed consent
• Diagnosis of multiple myeloma per IMWG criteria
• Patients must have progressive disease following 3 or more prior lines of therapy * Prior treatment must include a proteasome inhibitor, an immunomodulatory agent (IMiD), and an anti‐CD38 monoclonal antibody * Patients must not be candidates for regimens known to provide clinical benefit in relapsed or refractory multiple myeloma based on the investigator’s judgement * If a patient declines such therapy, this must be recorded in the study files
• 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 serum protein electrophoresis (SPEP) or * >= 200 mg/24 hour urine collection by urine protein electrophoresis (UPEP) or * Serum free light chain levels > 100 mg/L (milligrams/liter involved light chain) and an abnormal kappa/lambda 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 magnetic resonance imaging (MRI) at the time of diagnosis or study enrollment, OR the presence of lesions (>= 3) on positron emission tomography (PET)/computed tomography (CT) scan
• Absolute neutrophil count (ANC) >= 1.0 x 10^9/L without growth factor support for 7 days (14 days if pegfilgastrim). However, patient can be enrolled if the ANC are low due to disease
• Platelets (plt) >= 50 x 10^9/L without transfusion for 7 days. However, patient can be enrolled if the platelets are low due to disease
• Hemoglobin >= 8.0 g/dl, transfusion support permitted
• Aspartate aminotransferase (AST/serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT/serum glutamate pyruvate transaminase [SGPT]) =< 3.0 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
• Left ventricular ejection fraction by echocardiography (ECHO) or multigated acquisition scan (MUGA) of >= 40% performed
• Participants must have a performance status of 0-2 based on Eastern Cooperative Oncology Group (ECOG) criteria. Participants with poor performance status (3-4) based solely on bone pain will be eligible, provided there is documentation to verify this
• For people of child bearing potential negative serum or urine pregnancy test (sensitivity of at least 25 mIU/mL) at screening

Exclusion Criteria

• 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 with respect to the concurrent malignancy at the time of study entry
• Participants must not have life-threatening comorbidities
• Known human immunodeficiency virus (HIV) disease (requires negative test for clinically suspected HIV infection)
• 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 glucose-6-phosphate dehydrogenase (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