High Dose Ascorbic Acid for Plasma Cell Disorders

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

This study is testing whether high doses of vitamin C can help people with relapsed multiple myeloma feel better when combined with a lower dose of a chemotherapy drug and a stem cell transplant.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 18 (estimated)
• Ages: 18 Years to 100 Years
• Sex: All
• Sponsor: University of Arkansas (Academic / other)
• Drugs / interventions: daratumumab, chemotherapy
• Locations: 1 site (Little Rock, Arkansas)
• Trial ID: NCT06313502 on ClinicalTrials.gov

What this trial studies

This clinical trial evaluates the safety and effectiveness of High Dose Ascorbic Acid (HDAA) combined with a reduced dose of melphalan and autologous stem cell transplantation (ASCT) in patients with relapsed refractory multiple myeloma. Participants will receive a test dose of HDAA followed by varying doses in conjunction with melphalan and ASCT. The study aims to determine tumor response and assess safety and tolerability through lab tests and scans at scheduled infusion timepoints. It is a single-arm Phase I trial focusing on patients who have undergone multiple lines of therapy.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with relapsed refractory multiple myeloma who have received at least three prior lines of therapy.

Not a fit: Patients who have not been previously treated or those with early-stage multiple myeloma may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could provide a more effective and tolerable treatment option for patients with relapsed refractory multiple myeloma.

How similar studies have performed: While this approach is novel, other studies have explored the use of high-dose ascorbic acid in cancer treatment, but results have been variable.

Eligibility criteria

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 dose may be utilized:

   * M-protein quantities ≥ 0.5 gm/dl by SPEP
   * ≥ 200 mg/24-hour urine collection by UPEP
   * serum-free light chain levels \> 100 mg/L (milligrams/liter involved light chain) and an abnormal kappa/lambda (κ/λ) ratio in subjects without detectable serum or urine m-protein
   * a serum IgA level ≥ 500 mg/dL for subjects with immunoglobulin class A (IgA) myeloma whose disease can only be reliably measured by quantitative immunoglobulin measurement
   * Non-secretory subjects are eligible provided the subject has \> 20% BM plasmacytosis, OR multiple plasmacytomas or lesions (≥3) on MRI at the time of diagnosis or study enrollment, OR the presence of lesions (≥ 3) on PET/Computerized Tomography (CT) scan.
6. Adequate organ function reflects the following:

   * Absolute neutrophil count (ANC) ≥ 0.5 x 109/L without growth factor support for 7 days (14 days if pegfilgastrim).
   * Platelets ≥ 25 x 109/L without transfusion for 7 days. However, subject can be enrolled if the ANC and platelets are low due to disease
   * Potassium within normal limits or correctable with supplements
   * Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x 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 \< 1.5 x ULN
   * Ejection fraction by ECHO or MUGA of ≥ 40% performed
   * Subjects must have adequate pulmonary function studies (PFTs) \> 50% of predicted on mechanical aspects (forced expiratory volume, forced vital capacity) and \> 50% of predicted (adjusted for hemoglobin) on diffusion capacity. If the participant is unable to complete PFTs due to disease-related pain or other circumstances that make it difficult to reliably perform PFTs, documentation of pulmonary function adequate for transplant will occur via a CT scan without evidence of major pulmonary disease and arterial blood gas results.
7. Subjects must have a performance status of 0-2 based on ECOG performance criteria. Subjects with poor performance status (3-4) based solely on bone pain will be eligible if there is documentation to verify this.
8. Negative serum or urine pregnancy test (sensitivity of at least 25 mIU/mL) at screening.

Exclusion Criteria:

1. Prior allogeneic transplant.
2. Known hypersensitivity or allergy to ascorbic acid or melphalan, or any Grade 3 or higher AE as a result of test dose given during screening (15 gm).
3. Subjects must not have a concurrent malignancy unless it can be adequately treated by non-chemotherapeutic intervention. Participants may have a history of prior malignancy without any chemotherapy within 365 days of study entry AND life expectancy exceeding 5 years at the time of study entry.
4. Subjects must not have life-threatening comorbidities as assessed by the investigator.
5. History or evidence of MM associated with immunodeficiency states (e.g., hereditary immune deficiency, human immunodeficiency virus (HIV), organ transplant, or leukemia).
6. Known HIV disease (requires negative test for clinically suspected HIV infection).
7. Evidence of CNS myeloma.
8. 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.
9. Concurrent use of coumadin (warfarin).
10. Glucose-6-phosphate dehydrogenase deficiency as defined by blood test at screening visit.
11. Pre-existing renal insufficiency or renal failure, a known history of renal stones, or who are undergoing dialysis.
12. Diabetic subjects who are insulin dependent.
13. Any other condition that, in the opinion of the investigator, might interfere with the safe conduct of the study.

Where this trial is running

Little Rock, Arkansas

• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States (Recruiting)

Study contacts

• Principal investigator: Carolina Schinke, MD — University of Arkansas
• Study coordinator: Aaron Holley

Conditions Plasma Cell Disorder