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

Overseen by Christopher Strouse, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Michael Tomasson

Must not be taking: Coumadin

Disqualifiers: HIV, G6PD deficiency, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a combination of a chemotherapy drug and high doses of vitamin C in patients with a type of blood cancer that has not responded to other treatments. The goal is to kill cancer cells and improve the effectiveness of chemotherapy. High-dose vitamin C has been proposed as a potential therapeutic approach for patients with advanced tumors who failed previous treatment with chemotherapy.

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.

What evidence supports the effectiveness of the drug combination of high-dose Vitamin C and low-dose Melphalan for treating multiple myeloma?

Research shows that a combination of melphalan, arsenic trioxide, and ascorbic acid (Vitamin C) was effective in treating multiple myeloma, with 48% of patients showing positive responses. Another study found that adding arsenic trioxide and ascorbic acid to high-dose melphalan was safe and well-tolerated, with an 85% overall response rate. ^{1 2 3 4 5}

Is the combination of high-dose Vitamin C and low-dose Melphalan safe for treating multiple myeloma?

Research shows that the combination of Vitamin C and Melphalan, sometimes with other drugs, is generally safe and well-tolerated in patients with multiple myeloma. Some studies reported mild to moderate side effects like fever, fatigue, and pain, but no severe or life-threatening issues were common. ^{1 4 5 6 7}

How is the drug combination of high-dose Vitamin C and low-dose Melphalan unique for treating multiple myeloma?

This treatment is unique because it combines high-dose Vitamin C, which selectively kills multiple myeloma cells by generating reactive oxygen species, with low-dose Melphalan, a chemotherapy drug, to enhance effectiveness while potentially reducing side effects. This combination targets tumor cells more specifically, offering a novel approach compared to traditional high-dose chemotherapies that can harm normal cells. ^{4 5 8 9 10}

Research Team

Christopher Strouse, MD

Principal Investigator

University of Iowa

Eligibility Criteria

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 am currently taking Coumadin (warfarin).

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

I do not have any severe health conditions that could threaten my life.

Trial Timeline

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

Treatment Details

Interventions

• Ascorbate (Other)
• Melphalan (Alkylating agents)

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.

Participant Groups

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 Canada, Japan, China, Switzerland for the following indications:

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+

Dr. Afable

University of Iowa

Chief Medical Officer since 2005

MD from Loyola Stritch School of Medicine, MPH from the University of Illinois

Joel Harris

University of Iowa

Chief Executive Officer since 2023

B.A. in Economics from the University of Iowa, Post-baccalaureate Certificate in Narrative Communications from Northwestern University

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2015]

2. United States 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. [2018]

3. Italy pubmed.ncbi.nlm.nih.gov

Phase II multicenter study of arsenic trioxide, ascorbic acid and dexamethasone in patients with relapsed or refractory multiple myeloma. [2018]

4. England 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. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Arsenic trioxide with ascorbic acid and high-dose melphalan: results of a phase II randomized trial. [2021]

6. England 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. [2019]

7. United States 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. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Multiple Myeloma Tumor Cells are Selectively Killed by Pharmacologically-dosed Ascorbic Acid. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Pharmacological dose ascorbic acid administration in relapsed refractory multiple myeloma patients. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Antitumor effect of pharmacologic ascorbate in the B16 murine melanoma model. [2015]