High Dose Ascorbic Acid for Plasma Cell Disorders

NCT03602235 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 201804754
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Rate of minimal residual disease (MRD) negativity through bone marrow testing and imaging

  Through 28 days after the end of treatment

• Overall response rate based on International Myeloma Working Group (IMWG) criteria

  Through 24 months after the end of treatment

• Categorize and quantify adverse events compared to historical control

  Up to 24 months following the end of treatment for the last patient

• Oxidative stress parameters in plasma through blood testing

  Through 24 months after the end of treatment

Study Arms (1)

Low dose melphalan + high dose ascorbate acid (HDAA)

EXPERIMENTAL

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; Drug: Melphalan

Interventions

Ascorbate OTHER

Ascorbate is in the vitamin drug class

Also known as: Ascorbate Acid; Ascorbic Acid for Injection, USP

Low dose melphalan + high dose ascorbate acid (HDAA)

Melphalan DRUG

Melphalan is an alkylating agent coupled to an amino acid

Also known as: L-phenylamine mustard; L-PAM; L-Sarcolysin

Low dose melphalan + high dose ascorbate acid (HDAA)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Christopher Strouse: lead
• University of Iowa: collaborator

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Ascorbic Acid; Injections; Melphalan

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Sugar Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Hydroxy Acids; Carbohydrates; Drug Administration Routes; Drug Therapy; Therapeutics; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Christopher Strouse, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: July 17, 2018
• First Posted: July 26, 2018
• Study Start: March 5, 2019
• Primary Completion: July 1, 2024
• Study Completion: September 3, 2025
• Last Updated: October 21, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)