What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, such as low dose melphalan and high dose ascorbate acid, have known side effects. Melphalan can cause hematological toxicities like leukopenia, thrombocytopenia, and anemia, as well as gastrointestinal issues such as nausea, vomiting, and mucositis. High dose ascorbate acid may lead to gastrointestinal discomfort and, rarely, kidney stones or oxalate nephropathy. Combining these treatments may result in compounded side effects, particularly impacting blood cell counts and gastrointestinal health.

What prior FDA approvals exist?

Melphalan, a DNA cross-linking agent, has been a cornerstone in the treatment of Multiple Myeloma, often used in combination with other drugs like dexamethasone. High dose melphalan is commonly used in autologous stem cell transplantation. Other FDA-approved treatments for Multiple Myeloma include proteasome inhibitors (e.g., bortezomib), immunomodulatory drugs (e.g., lenalidomide, pomalidomide), and monoclonal antibodies (e.g., elotuzumab, daratumumab). These treatments target different pathways to inhibit cancer cell growth and survival.

What other types of research exist?

Promising novel alternatives for Multiple Myeloma treatment in 2024 include CAR T-cell therapies (e.g., idecabtagene vicleucel, ciltacabtagene autoleucel), bispecific antibodies (e.g., teclistamab), and next-generation proteasome inhibitors (e.g., ixazomib). These therapies have shown significant efficacy in clinical trials and are being integrated into treatment protocols for relapsed or refractory Multiple Myeloma.

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

Phase 1

Recruiting

Led By Christopher Strouse, MD

Research Sponsored by Michael Tomasson

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have progressive disease following 3 or more prior lines of therapy

Diagnosis of multiple myeloma per IMWG criteria

Must not have

Concurrent use of Coumadin (warfarin)

Patients with a history of oxalate renal stones or a known history of multiple renal stones

Timeline

Screening 3 weeks

Treatment Varies

Follow Up through 28 days after the end of treatment

Awards & highlights

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include those typical of chemotherapy like nausea, fatigue, hair loss, increased risk of infection due to lowered blood counts; plus possible kidney stone formation and interference with diabetes monitoring.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My condition worsened after 3 or more treatments.

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I have been diagnosed with multiple myeloma.

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I have been treated with a proteasome inhibitor, an IMiD, and an anti-CD38 antibody.

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I am able to get out of my bed or chair and move around.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I am currently taking Coumadin (warfarin).

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

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

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I have been diagnosed with HIV.

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

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I have G6PD deficiency.

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I have another cancer that can be treated without chemotherapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ through 28 days after the end of treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~through 28 days after the end of treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and through 28 days after the end of treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of treatment related adverse events as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) Version 4.03

Secondary study objectives

Categorize and quantify adverse events compared to historical control

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

Oxidative stress parameters in plasma through blood testing

+1 more

Side effects data

From 2024 Phase 1 & 2 trial • 25 Patients • NCT03508726

67%

Nausea

67%

Lymphocyte count decreased

50%

Hypertension

50%

Investigations - Other, specify

50%

Fatigue

33%

Alanine aminotransferase increased

33%

Dermatitis radiation

33%

Dry mouth

33%

Anemia

33%

Neutrophil count decreased

33%

White blood cell decreased

33%

Headache

17%

Urinary tract infection

17%

Abdominal pain

17%

Skin and subcutaneous tissue disorders - Other, specify

17%

Alkaline phosphatase increased

17%

Aspartate aminotransferase increased

17%

Hypoalbuminemia

17%

Infections and infestations - Other, specify

17%

Tumor pain

17%

Blood bilirubin increased

17%

Hyperglycemia

17%

Pain

17%

Rash maculo-papular

17%

Thrush

17%

Gastrointestinal disorders - Other, specify

17%

Vomiting

17%

Colitis

17%

Rectal pain

17%

Diarrhea

17%

Hemorrhoids

17%

Platelet count decreased

17%

Anorexia

17%

Presyncope

17%

Dysuria

17%

Cough

17%

Dyspnea

17%

Hyperhidrosis

17%

Pruritus

100%

80%

60%

40%

20%

Study treatment Arm

Phase I: Ascorbate 75 mg IV Infusion

Phase II: Ascorbate 75 mg IV Infusion

Trial Design

1Treatment groups

Experimental Treatment

Group I: Low dose melphalan + high dose ascorbate acid (HDAA)Experimental Treatment2 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Melphalan

2008

Completed Phase 3

~1500

0 / 11Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Multiple Myeloma, such as low dose melphalan and high dose ascorbate acid, work through distinct mechanisms. Melphalan is a DNA cross-linking agent that disrupts DNA replication, leading to cancer cell death. High dose ascorbate acid acts as a pro-oxidant, generating reactive oxygen species that induce oxidative stress and cytotoxicity in cancer cells. This combination is important for Multiple Myeloma patients as it targets cancer cells through multiple pathways, potentially increasing treatment efficacy and reducing damage to normal cells.

Separate mechanisms for procarbazine spermatotoxicity and anticancer activity.Pro-oxidant properties of methotrexate: evaluation and prevention by an anti-oxidant drug.Influence of reducing compounds on the formation of DNA-protein cross-links in HL-60 cells induced by hexavalent chromium.