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

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.

Conditions

• Plasma Cell Disorder

Interventions

DRUG

75gm 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.

DRUG

100gm 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.

DRUG

125gm 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.

Sponsors & Collaborators

• University of Iowa

  collaborator OTHER

• University of Arkansas

  lead OTHER

Principal Investigators

• Carolina Schinke, MD · University of Arkansas

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-07-19

Primary Completion

2027-04-30

Completion

2028-04-30

FDA Drug

Yes

Countries

• United States

Study Locations