High Dose Ascorbic Acid (HDAA) in Patients With Plasma Cell Disorders
University of Arkansas
Summary
The purpose of this research is to evaluate whether HDAA in combination with a single dose of 100 mg/m2 IV melphalan followed by autologous stem cell transplantation (ASCT) is safe and effective for subjects with relapsed refractory multiple myeloma. The proposed melphalan dose is 50% of the current standard myeloablative dose (200 mg/m2). Based on our preclinical data, the investigator hypothesize that the combination of reduced dose melphalan with IV HDAA will have high efficacy and tolerability Primary Objective To determine tumor response using International Myeloma Working Group (IMWG) criteria (see Appendix B). Secondary Objectives Objectives: 1. Determine the safety and tolerability of HDAA in combination with reduced dose melphalan conditioning and autologous stem cell transplantation (ASCT) in relapsed refractory multiple myeloma subjects. 2. Determine the rate of Minimal Residual Disease (MRD) negativity at time point of response assessment using 8 color flow cytometry on BM sample. Functional imaging, such as positron emission tomography (PET) scan and magnetic resonance imaging (MRI), will also be performed to assess the disease status. 3. Categorize and quantify adverse events compared to historical control. 4. Determine quality of life parameters using standardized health-related quality of life measures 5. Determine oxidative stress parameters in plasma during treatment.
Description
This is a single arm Phase I trial evaluating safety, tolerability, and efficacy of High Dose Ascorbic Acid (HDAA) in patients with plasma cell disorders. This is a single arm study. Subjects will receive a test dose of HDAA alone at screening (15gm), then proceed to either 75, 100, or 125 gm, depending upon the cohort) on day -4, HDAA combined with melphalan 100 mg/m2 on day -1, and ASCT on day 0. Four additional HDAA doses (each of which is either 75, 100, or 125 gm, depending upon the cohort) will then be administered 3 days apart on D+2, D+5, D+8 and D+11, followed by weekly doses of the c…
Eligibility
- Age range
- 18–100 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Subject has provided informed consent. 2. Participants who are 18 years of age or older 3. Subjects who have been previously treated with 3 or more lines of therapy (i.e., proteasome inhibitors, immunomodulatory agents such as lenalidomide, and monoclonal antibodies such as daratumumab) and have progressed within past 6 months. 4. Subjects who have at least 1x106/kg CD34 stem cells in storage 5. Subjects must have measurable disease (as determined by the UAMS clinical lab), including at least one of the criteria below. Tests performed as SOC within 30 days of the first…
Interventions
- Drug75gm HDAA
Initiation: Subjects will receive a test dose of ascorbate (15 gm), during screening period, prior to starting therapy. Dose: After successfully completing the test dose, subjects will receive 75gm of ascorbate infusion. Dose modifications will not be made for weight or body surface area. Administration: Infusion time is set to occur at 120 minutes +/-10 minutes but may be adjusted for subject comfort. The infusion rate should not exceed 500 mL/hour without consulting with PI. Changes in infusion rates should be recorded.
- Drug100gm HDAA
Initiation: Subjects will receive a test dose of ascorbate (15 gm), during screening period, prior to starting therapy. Dose: After successfully completing the test dose, subjects will receive 100gm of ascorbate infusion. Dose modifications will not be made for weight or body surface area. Administration: Infusion time is set to occur at 180 minutes +/-10 minutes but may be adjusted for subject comfort. The infusion rate should not exceed 500 mL/hour without consulting with PI. Changes in infusion rates should be recorded.
- Drug125gm HDAA
Initiation: Subjects will receive a test dose of ascorbate (15 gm), during screening period, prior to starting therapy. Dose: After successfully completing the test dose, subjects will receive 125gm of ascorbate infusion. Dose modifications will not be made for weight or body surface area. Administration: Infusion time is set to occur at 240 minutes +/-10 minutes but may be adjusted for subject comfort. The infusion rate should not exceed 500 mL/hour without consulting with PI. Changes in infusion rates should be recorded.
Location
- University of Arkansas for Medical SciencesLittle Rock, Arkansas