High Dose Ascorbic Acid for Plasma Cell Disorders

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

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.

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Other: Ascorbate; Drug: Melphalan

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Low dose melphalan + high dose ascorbate acid (HDAA); Patients will receive a test dose of 15g of HDAA prior to starting treatment dose. This will be mainly to rule out allergic reactions. HDAA + Melphalan: HDAA on day 1 and day 4 in combination with melphalan 12.5 mg/m2, followed by 2 additional doses of HDAA on day 2 and day 5. A 3 + 3 cohort method will be used for this study. After successfully completing the test dose, subjects will receive 50gms, 75gms and 100gms of ascorbate per infusion in 3 different cohorts. Dose modifications are not made for weight or body surface area.

Other: Ascorbate; Ascorbate is in the vitamin drug class; Other Names: Ascorbate Acid; Ascorbic Acid for Injection, USP; Drug: Melphalan; Melphalan is an alkylating agent coupled to an amino acid; Other Names: L-phenylamine mustard; L-PAM; L-Sarcolysin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of treatment related adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03	Adverse events occuring within the DLT assessment window which do not resolve in less than 72 hours and are not clearly and incontrovertibly due to extraneous causes.	First day of treatment through 28 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of minimal residual disease (MRD) negativity through bone marrow testing and imaging	MRD will be determined by highly sensitive, eight color flow on bone marrow sample. Functional imaging, such as PET scan and MRI will also be performed to assess the disease status.	Through 28 days after the end of treatment
Overall response rate based on International Myeloma Working Group (IMWG) criteria	Response to treatment will be assessed by IMWG criteria.	Through 24 months after the end of treatment
Categorize and quantify adverse events compared to historical control	The number and severity of all adverse events will be summarized by simple descriptive statistics and compared to a historical control.	Up to 24 months following the end of treatment for the last patient
Oxidative stress parameters in plasma through blood testing	Blood will be drawn and serum iron, TIBC, serum ferritin and transferrin saturation levels tested.	Through 24 months after the end of treatment

Collaborators and Investigators

• Sponsor: Christopher Strouse
• Collaborators: University of Iowa
• Investigators: Principal Investigator: Christopher Strouse, MD, University of Iowa

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2019
• Primary Completion (Actual): July 1, 2024
• Study Completion (Actual): September 3, 2025

Study Registration Dates

• First Submitted: July 17, 2018
• First Submitted That Met QC Criteria: July 17, 2018
• First Posted (Actual): July 26, 2018

Study Record Updates

• Last Update Posted (Estimated): October 21, 2025
• Last Update Submitted That Met QC Criteria: October 17, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Amino Acids, Peptides, and Proteins; Organic Chemicals; Therapeutics; Drug Administration Routes; Drug Therapy; Hydrocarbons; Carbohydrates; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Amino Acids; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Melphalan; Ascorbic Acid; Injections
• Other Study ID Numbers: 201804754

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No