High Dose Ascorbic Acid (HDAA) in Patients with Plasma Cell Disorders

Description

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.

Trial Eligibility

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

Study Info

Interventions

Locations Recruiting

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