Clinical trial · Interventional
Combining Active and Passive DNA Hypomethylation
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
NCT03999723CI-TRIAL-00076200EVI-3recruitingPhase 2ClinicalTrials.gov clinicaltrialsProvenance
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
This is a multicentre, randomized, parallel-group, placebo-controlled, double-blind phase 2 study of the efficacy and safety of oral vitamin C supplement in combination with azacitidine in patients with higher-risk MDS, CMML-2 or low-blast count AML. The primary purpose is to investigate if oral vitamin C supplementation to azacitidine, compared with azacitidine + placebo, can increase the effectiveness of epigenetic therapy in patients with higher-risk myeloid malignancies, who are not candidates for allogeneic hematopoietic stem cell transplantation.
Conditions
Conditions (3)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Acute Myeloid Leukemia | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
| Chronic Myelomonocytic Leukemia | Chronic Myelomonocytic Leukemia | ONTOLOGY_EXACT | 0.98 |
| Myelodysplastic Syndromes | Myelodysplastic Syndrome | ALIAS | 0.90 |
Interventions
Interventions (2)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Placebo | Dietary Supplement | — | UNRESOLVED |
| Vitamin C | Dietary Supplement | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- type
- EXPERIMENTAL
- label
- Vitamin C
- description
- Oral vitamin C (ascorbic acid) will be given in a dose of 1000 mg daily (two capsules of 500 mg once daily) starting day 1 in the 1st azacitidine (AZA) cycle (D1/C1) and continuing until discontinuation of AZA or end of study, whichever occurs earlier.
- interventionNames
- Dietary Supplement: Vitamin C
- type
- PLACEBO_COMPARATOR
- label
- Placebo
- description
- Placebo will be administered orally as two capsules once daily that look and taste identical to the capsules containing vitamin C. Treatment will start day 1 in the 1st azacitidine (AZA) cycle (D1/C1) and continuing until discontinuation of AZA or end of study, whichever occurs earlier. The content of the placebo capsules is glucose monohydrate, potato starch, gelatin, magnesium stearate and talc.
- interventionNames
- Dietary Supplement: Placebo
Primary outcomes (1)
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
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)
References
Publications (2)
- BACKGROUNDAaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, Filiberti A, Flechtner H, Fleishman SB, de Haes JC, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst. 1993 Mar 3;85(5):365-76. doi: 10.1093/jnci/85.5.365. PMID 8433390
- BACKGROUNDGoswami P, Oliva EN, Ionova T, Else R, Kell J, Fielding AK, Jennings DM, Karakantza M, Al-Ismail S, Lyness J, Collins GP, McConnell S, Langton C, Al-Obaidi MJ, Oblak M, Salek S. Paper and electronic versions of HM-PRO, a novel patient-reported outcome measure for hematology: an equivalence study. J Comp Eff Res. 2019 May;8(7):523-533. doi: 10.2217/cer-2018-0108. Epub 2019 Apr 30. PMID 31037971