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

Status: Recruiting
Location: See location...
Intervention Type: Drug
Study Type: Interventional
Study Phase: Phase 1
SUMMARY

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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Maximum Age: 100
Healthy Volunteers: f
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• Subject has provided informed consent.

• Participants who are 18 years of age or older

• 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.

• Subjects who have at least 1x106/kg CD34 stem cells in storage

• 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.

• 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.

• 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.

• Negative serum or urine pregnancy test (sensitivity of at least 25 mIU/mL) at screening.

Locations
United States
Arkansas
University of Arkansas for Medical Sciences
RECRUITING
Little Rock
Contact Information
Primary
Aaron Holley
jaholley@uams.edu
501-686-8274
Backup
Beth Scanlan
bscanlan@uams.edu
501-686-8274
Time Frame
Start Date: 2024-07-19
Estimated Completion Date: 2028-04
Participants
Target number of participants: 18
Treatments
Experimental: 75gm HDAA + Melphalan 100mg/m2
Subjects will receive HDAA alone (75gm) on day -4, HDAA combined with melphalan 100 mg/m2 on day -1, and ASCT on day 0. Four additional HDAA doses (75gm) will then be administered 3 days apart on D+2, D+5, D+8 and D+11, followed by weekly doses of the corresponding dose of HDAA for four additional weeks. On day, D-1, when both drugs are given, melphalan should be given first
Experimental: 100gm HDAA + Melphalan 100mg/m2
Subjects will receive HDAA alone (100gm) on day -4, HDAA combined with melphalan 100 mg/m2 on day -1, and ASCT on day 0. Four additional HDAA doses (100gm) will then be administered 3 days apart on D+2, D+5, D+8 and D+11, followed by weekly doses of the corresponding dose of HDAA for four additional weeks. On day, D-1, when both drugs are given, melphalan should be given first
Experimental: 125gm HDAA + Melphalan 100mg/m2
Subjects will receive HDAA alone (125gm) on day -4, HDAA combined with melphalan 100 mg/m2 on day -1, and ASCT on day 0. Four additional HDAA doses (125gm) will then be administered 3 days apart on D+2, D+5, D+8 and D+11, followed by weekly doses of the corresponding dose of HDAA for four additional weeks. On day, D-1, when both drugs are given, melphalan should be given first
Sponsors
Leads: University of Arkansas
Collaborators: University of Iowa

This content was sourced from clinicaltrials.gov

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