High-Dose Vitamin C + Low-Dose Melphalan for Multiple Myeloma

Overseen By Christopher Strouse, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Michael Tomasson

Must not be taking: Coumadin

Disqualifiers: HIV, G6PD deficiency, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and potential benefits of combining high-dose vitamin C with a low dose of melphalan, a chemotherapy drug, for individuals with multiple myeloma, a type of blood cancer. The focus is on patients whose disease has worsened despite trying at least three different treatments, including specific drugs. Those who have already tried these treatments but are not eligible for other beneficial regimens may be suitable for this study. Participants should not have allergies to the study drugs or certain health conditions, such as a history of kidney stones or diabetes requiring frequent blood sugar monitoring. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use Coumadin (warfarin) while participating. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that using high-dose vitamin C with low-dose melphalan may help treat multiple myeloma, a type of blood cancer. In previous studies, most patients tolerated this combination well.

For instance, one study found that combining melphalan with arsenic trioxide and vitamin C was safe for most participants, with about 48% responding positively. Another study suggested that high-dose vitamin C, administered through an IV, might be a strong anti-cancer treatment.

While these findings are promising, this trial remains in the early stages. The main goal is to ensure the treatment's safety for people. Participants will receive varying amounts of vitamin C to check for allergic reactions or side effects. This trial aims to collect crucial safety information to guide future research. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Researchers are excited about using high-dose Vitamin C (ascorbate) with low-dose Melphalan for multiple myeloma because it offers a novel approach to treatment. Unlike traditional therapies that primarily involve chemotherapy and targeted drugs, this combination utilizes high doses of Vitamin C to potentially enhance the cancer-killing effects of Melphalan. Vitamin C is thought to act as a pro-oxidant in high concentrations, which can lead to increased cancer cell death while sparing healthy cells. This unique mechanism may improve treatment outcomes and reduce side effects compared to existing options.

What evidence suggests that this treatment might be an effective treatment for multiple myeloma?

This trial will evaluate the combination of high doses of vitamin C with low doses of melphalan for treating multiple myeloma, a type of blood cancer. Studies have shown that this combination might kill cancer cells more effectively than melphalan alone. Specifically, earlier research demonstrated that this treatment worked in 48% of patients with multiple myeloma. High doses of vitamin C have been linked to better cancer survival rates, and melphalan is a strong drug for killing myeloma cells. Together, they may offer a promising way to treat this condition. ^{1 3 6 7 8}

Who Is on the Research Team?

Christopher Strouse, MD

Principal Investigator

University of Iowa

Are You a Good Fit for This Trial?

This trial is for adults with multiple myeloma who've tried at least three prior treatments, including specific inhibitors and antibodies. They must have measurable disease progression but not be suitable for other beneficial regimens. Participants need good organ function, no severe comorbidities or certain infections, and can't be on warfarin or have a history of significant kidney stones.

Inclusion Criteria

I am not a candidate for known effective treatments for my relapsed or refractory multiple myeloma.

My condition worsened after 3 or more treatments.

Subject has provided informed consent

Exclusion Criteria

I have had kidney stones made of oxalate or multiple kidney stones before.

I am currently taking Coumadin (warfarin).

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Test Dose

Participants receive a 15-gram test dose of high-dose ascorbic acid to rule out allergic reactions

1 day

1 visit (in-person)

Treatment

Participants receive up to 3 cycles of treatment with high-dose ascorbic acid and melphalan, with dose escalation from 50g to 100g of ascorbic acid

12 weeks

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and response rate

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Ascorbate
• Melphalan

Trial Overview The study tests high doses of Vitamin C (ascorbic acid) combined with low dose melphalan chemotherapy in patients whose multiple myeloma has relapsed after previous treatments. It's an early-phase trial focusing on safety and initial signs of effectiveness.

How Is the Trial Designed?

Group I: Low dose melphalan + high dose ascorbate acid (HDAA) Experimental Treatment 2 Interventions

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.

Ascorbate is already approved in United States, European Union, Canada, Japan, China, Switzerland for the following indications:

Approved in United States as Ascorbic Acid for:

• Scurvy
• Dietary supplement

Approved in European Union as Vitamin C for:

• Scurvy
• Dietary supplement

Approved in Canada as Ascorbate for:

• Scurvy
• Dietary supplement

Approved in Japan as Ascorbic Acid for:

• Scurvy
• Dietary supplement

Approved in China as Vitamin C for:

• Scurvy
• Dietary supplement

Approved in Switzerland as Ascorbate for:

• Scurvy
• Dietary supplement

Who Is Running the Clinical Trial?

Michael Tomasson

Lead Sponsor

Trials

3

Recruited

410+

Christopher Strouse

Lead Sponsor

Trials

3

Recruited

410+

University of Iowa

Collaborator

Trials

486

Recruited

934,000+

Published Research Related to This Trial

In a phase 2 study involving 35 newly diagnosed multiple myeloma patients, the combination of bortezomib, ascorbic acid, and melphalan (BAM) resulted in a 74% response rate, with 94% of patients achieving disease control.

BAM treatment was found to be well-tolerated, with manageable side effects, making it a promising frontline therapy for multiple myeloma without the use of steroids or immunomodulatory drugs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib, ascorbic acid and melphalan (BAM) therapy for patients with newly diagnosed multiple myeloma: an effective and well-tolerated frontline regimen. Berenson, JR., Yellin, O., Woytowitz, D., et al.[2015]

In a study of 55 multiple myeloma patients with renal failure, high-dose melphalan-based autologous stem cell transplantation (ASCT) resulted in a very good partial response (VGPR) in 58% of patients, demonstrating its efficacy even in those with compromised kidney function.

The median overall survival (OS) was 76 months and median progression-free survival (PFS) was 55 months, comparable to patients with normal renal function, indicating that ASCT can be a valuable treatment option despite the risks of significant toxicities like febrile neutropenia and severe mucositis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Extending autologous transplantation as first line therapy in multiple myeloma patients with severe renal impairment: a retrospective study by the SFGM-TC. Augeul-Meunier, K., Chretien, ML., Stoppa, AM., et al.[2019]

Pharmacologic ascorbate (vitamin C) demonstrated significant antitumor effects in melanoma, reducing tumor size in murine models compared to saline controls, with a strong statistical significance (P < 0.0001).

Ascorbate was found to be as effective or more effective than the standard chemotherapeutic agent dacarbazine, but did not show synergy when combined with other treatments, indicating its potential as a standalone therapy in melanoma management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor effect of pharmacologic ascorbate in the B16 murine melanoma model. Serrano, OK., Parrow, NL., Violet, PC., et al.[2015]

In a phase 2 trial involving 20 patients with relapsed or refractory multiple myeloma, the combination of arsenic trioxide, dexamethasone, and ascorbic acid resulted in a 30% overall response rate and 80% of patients achieving at least stable disease.

The treatment was well tolerated, with most side effects being mild or moderate, and the median progression-free survival was 316 days overall, extending to 584 days for those who responded to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety results with the combination therapy of arsenic trioxide, dexamethasone, and ascorbic acid in multiple myeloma patients: a phase 2 trial. Abou-Jawde, RM., Reed, J., Kelly, M., et al.[2018]

In a phase II trial involving 48 patients with multiple myeloma, the combination of arsenic trioxide (ATO), melphalan, and ascorbic acid was found to be safe and well tolerated, with no significant adverse effects observed during the first 100 days post-autologous stem cell transplantation.

The treatment resulted in a complete response rate of 25% and an overall response rate of 85%, with a median progression-free survival of 25 months, indicating promising efficacy for this combination therapy in managing multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Arsenic trioxide with ascorbic acid and high-dose melphalan: results of a phase II randomized trial. Qazilbash, MH., Saliba, RM., Nieto, Y., et al.[2021]

The MAC combination therapy of melphalan, arsenic trioxide, and ascorbic acid showed a 48% objective response rate in 65 patients with multiple myeloma who had previously failed multiple treatments, indicating its efficacy as a new therapeutic option.

The treatment was well tolerated, with infrequent severe adverse events, and notably, 82% of patients with elevated serum creatinine levels at baseline experienced improvements during treatment, suggesting potential renal benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of melphalan, arsenic trioxide and ascorbic acid combination therapy in patients with relapsed or refractory multiple myeloma: a prospective, multicentre, phase II, single-arm study. Berenson, JR., Boccia, R., Siegel, D., et al.[2018]

An international multi-center study investigated the combination of arsenic trioxide, ascorbic acid, and dexamethasone for treating advanced multiple myeloma, suggesting a potential new treatment strategy.

The study highlights that reducing glutathione levels with ascorbic acid may enhance the effectiveness of arsenic trioxide in inducing growth inhibition and apoptosis in multiple myeloma cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II multicenter study of arsenic trioxide, ascorbic acid and dexamethasone in patients with relapsed or refractory multiple myeloma. Wu, KL., Beksac, M., van Droogenbroeck, J., et al.[2018]

Pharmacologically-dosed ascorbic acid (PAA) can selectively kill multiple myeloma (MM) tumor cells while sparing normal cells, which could help reduce the toxic effects of high-dose chemotherapy.

In both laboratory and animal studies, PAA demonstrated efficacy in inhibiting tumor formation in MM, suggesting it could be a promising treatment option either alone or in combination with traditional drugs like melphalan.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid. Xia, J., Xu, H., Zhang, X., et al.[2019]

In a small study of 4 relapsed refractory multiple myeloma patients, adding high-dose intravenous ascorbic acid (15 grams/week) to their chemotherapy regimen resulted in one complete response and very good partial responses in the others after 4 cycles.

This suggests that pharmacological doses of ascorbic acid may enhance the effectiveness of conventional chemotherapy in difficult-to-treat multiple myeloma, warranting further clinical studies with larger patient groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacological dose ascorbic acid administration in relapsed refractory multiple myeloma patients. Bolaman, AZ., Turgutkaya, A., Küçükdiler, HE., et al.[2022]

In a study involving 19 patients with multiple myeloma and renal insufficiency, palifermin allowed for the safe escalation of melphalan doses up to 180 mg/m², demonstrating its potential as a cytoprotective agent during intensive chemotherapy.

The overall incidence of severe oral mucositis (grade 3 or higher) was 53%, with a median duration of 6.5 days, indicating that while palifermin helps manage side effects, significant toxicity still occurs at higher melphalan doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melphalan 180 mg/m2 can be safely administered as conditioning regimen before an autologous stem cell transplantation (ASCT) in multiple myeloma patients with creatinine clearance 60 mL/min/1.73 m2 or lower with use of palifermin for cytoprotection: results of a phase I trial. Abidi, MH., Agarwal, R., Ayash, L., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5405162/

Multiple Myeloma Tumor Cells are Selectively Killed by ... In the 1970s, Cameron and Pauling reported that high doses of vitamin C increased survival of patients with cancer (Cameron and Pauling, 1976, ...

2. healthtree.org healthtree.org/myeloma/community/podcasts/melphalan-and-high-dose-iv-vitamin-c

Melphalan and High Dose IV Vitamin C for Myeloma It is typically used in high doses and remains the single most effective drug to kill myeloma, but has significant side effects. Dr. Yogesh Jethava of the ...

3. withpower.com withpower.com/trial/phase-1-multiple-myeloma-2-2019-a1d50

High-Dose Vitamin C + Low-Dose Melphalan for Multiple ... Research shows that a combination of melphalan, arsenic trioxide, and ascorbic acid (Vitamin C) was effective in treating multiple myeloma, with 48% of patients ...

4. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(17)30101-9/fulltext

Pharmacologic Ascorbate in Myeloma Treatment: Doses ... Ascorbic acid (vitamin C) has followed opaque paths in treating multiple myeloma, and other malignancies. In myeloma cells, ascorbate ...

5. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2019-00738

High Dose Ascorbic Acid and Low Dose Melphalan in ... Giving high dose ascorbic acid and low dose melphalan may work better in treating patients with multiple myeloma compared to low dose melphalan without high ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT00085345

Melphalan, Arsenic Trioxide, and Ascorbic Acid in Treating ... PURPOSE: This phase II trial is studying how well giving melphalan together with arsenic trioxide and ascorbic acid works in treating patients with relapsed or ...

7. jeccr.biomedcentral.com jeccr.biomedcentral.com/articles/10.1186/s13046-021-02134-y

High-dose intravenous vitamin C, a promising multi-targeting ... Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC).

8. siteman.wustl.edu siteman.wustl.edu/ncipdq/intravenous-vitamin-c-pdq-health-professional-version/

Intravenous Vitamin C (PDQ®)–Health Professional Version The addition of arsenic trioxide and ascorbic acid to high-dose melphalan was reported safe and well tolerated, Melphalan, 1iiDii. [19], Phase ...