high dose ascorbic acid for plasma cell disorders

Conditions: Multiple Myeloma

Summary: this is a phase i single-arm open-label clinical study primarily assessing the safety and secondarily, the relative efficacy of low dose melphalan + high dose ascorbate acid (hdaa) in relapsed refractory patients with multiple myeloma.

this is a phase 1 study for patients with relapsed refractory multiple myeloma. patients will receive a 15-gram test dose, and a maximum of 3 cycles, each composed of 4 doses of high-dose ascorbic acid (hdaa) and 2 doses of melphalan. this study will enroll 9 patients with relapsed refractory multiple myeloma. the starting dose of ascorbic acid will be 50 grams. using a 3+3 dose escalation, the dose will potentially increase to 75 grams then 100 grams.

Eligibility criteria:
inclusion criteria: * subject has provided informed consent. * diagnosis of multiple myeloma per imwg criteria(26) * 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. 4. subjects must have measurable disease, including at least one of the criteria below: * spep demonstrating m-protein quantities ≥ 0.5 g/dl * upep demonstrating monoclonal protein ≥ 200 mg/24hr * involved serum free light chain levels \> 100 mg/l and an abnormal kappa/lambda (κ/λ)ratio * 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 will qualify as measurable disease * non-secretory participants are eligible provided the participant has \> 20% bone marrow plasmacytosis * adequate organ function: * absolute neutrophil count (anc) ≥ 1.0 x 10\^9/l without growth factor support for 7 days * platelets (plt) ≥ 50 x 10\^9/l without transfusion for 7 days. * hemoglobin ≥ 8.0 g/dl, transfusion support permitted * aspartate aminotransferase (ast/sgot) and alanine aminotransferase (alt/sgpt) ≤ 3.0x 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. * international normalized ratio (inr) \< 1.5 x uln and partial thromboplastin time (ptt) \< 1.5 x uln * left ventricular ejection fraction by echo or muga of ≥ 40%. * participants must have a performance status of 0-2 based on ecog criteria. * 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 they have not had any chemotherapy within 365 days of study entry and their 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 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