Combining vitamin C with azacitidine for treating higher-risk blood cancers

Combining Active and Passive DNA Hypomethylation: A Randomized, Placebo-Controlled Phase II Study of the Efficacy and Safety of Oral Vitamin C in Combination With Azacitidine in Patients With Higher-Risk MDS, CMML-2 or Low-Blast Count AML

This study is testing if adding vitamin C to azacitidine treatment can help people with higher-risk blood cancers feel better and improve their outcomes.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 196 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Rigshospitalet, Denmark (other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 10 sites (Aalborg and 9 other locations)
• Trial ID: NCT03999723 on ClinicalTrials.gov

What this trial studies

This phase 2 clinical trial investigates the efficacy and safety of oral vitamin C supplementation in combination with azacitidine for patients with higher-risk myelodysplastic syndromes, acute myeloid leukemia, or chronic myelomonocytic leukemia. The study is multicenter, randomized, and double-blind, comparing vitamin C to a placebo while patients receive azacitidine treatment. Participants will be monitored through various evaluations, including bone marrow investigations and patient-reported outcomes, over a treatment duration of approximately 54 months. The goal is to determine if vitamin C can enhance the effectiveness of azacitidine in these patients.

Who should consider this trial

Good fit: Ideal candidates include patients with higher-risk myelodysplastic syndromes, chronic myelomonocytic leukemia, or low-blast count acute myeloid leukemia who are not eligible for stem cell transplantation.

Not a fit: Patients who are eligible for allogeneic stem cell transplantation or have received prior hypomethylating agents may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve treatment outcomes for patients with higher-risk myeloid malignancies.

How similar studies have performed: While the combination of vitamin C and azacitidine is a novel approach, previous studies have shown promise in using hypomethylating agents for similar conditions.

Eligibility criteria

Inclusion Criteria:

• Patients eligible for treatment with azacitidine with one of the following diagnoses according to World Health Organization 2016:

* MDS Higher-risk MDS according to the IPSS-R, i.e., intermediate- to very high-risk (IPSS-R score \> 3)
* CMML CMML with 10-29 percent marrow blasts without myeloproliferative disorder
* AML AML with 20-30 percent blasts (low-blast count AML)

Note: Patients with therapy-related MDS are eligible if they have not received radiation or chemotherapy for six months.

Exclusion Criteria:

* Patient eligible for allogeneic stem cell transplantation
* Prior therapy with hypomethylating agents
* Any matter constituting an exclusion criterion for treatment with azacitidine
* Patient receiving other active cancer treatment, including investigational agents, with the exception of hydroxyurea for white blood cell (WBC) control, G-CSF, and low permanent doses of steroid (≤ 25 mg oral prednisolone per day) for inflammatory disorders
* Therapeutic radiation or chemotherapy within the past 6 months
* History of allergic reactions to ascorbic acid
* History of kidney or urinary tract stones requiring intervention within the past year
* Lack of ability to understand the information given, or lack of willingness to sign a written informed consent document
* Unwillingness to comply with the protocol
* Unwillingness to discontinue any and all use of vitamin C medication/supplementation including multivitamin at least 3 days (but preferably longer) prior to inclusion and baseline sampling
* Planned azacitidine treatment after allogeneic stem cell transplantation
* Eastern Cooperative Oncology Group (ECOG) performance status ≥3
* Uncontrolled comorbidity including impaired hepatic function (total serum bilirubin \>1.5 × upper limit of the normal range (ULN), serum alanine transaminase \>3 × ULN, chronic hepatitis with decompensated cirrhosis), disabling psychiatric disease, severe neurologic disease, severe metabolic disease, or severe cardiac disease (NYHA class 3-4)

Where this trial is running

Aalborg and 9 other locations

• Aalborg University Hospital — Aalborg, Denmark (RECRUITING)
• Aarhus University Hospital — Aarhus, Denmark (RECRUITING)
• Rigshospitalet — Copenhagen, Denmark (RECRUITING)
• Herlev University Hospital — Copenhagen, Denmark (RECRUITING)
• Odense University Hospital — Odense, Denmark (ACTIVE_NOT_RECRUITING)
• Zealand University Hospital — Roskilde, Denmark (TERMINATED)
• Sahlgrenska University Hospital — Gothenburg, Sweden (RECRUITING)
• Skåne University Hospital — Lund, Sweden (RECRUITING)
• Karolinska University Hospital — Stockholm, Sweden (RECRUITING)
• Uppsala University Hospital — Uppsala, Sweden (RECRUITING)

Study contacts

• Principal investigator: Stine Ulrik Mikkelsen, MD, PhD — Rigshospitalet, Denmark
• Study coordinator: Kirsten Grønbæk, Prof., MD

Conditions: Myelodysplastic Syndromes, Acute Myeloid Leukemia, Chronic Myelomonocytic Leukemia, Vitamin C, Ascorbic acid, Azacitidine, Hypomethylating agents, Randomized, Placebo-Controlled Trial