UnknownNot Applicable

Epigenetics, Vitamin C, and Abnormal Blood Cell Formation - Vitamin C in Patients With Low-Risk Myeloid Malignancies

United States, Denmark109 participantsStarted 2017-11-21

Plain-language summary

The primary purpose of this multi-centre, randomized, placebo-controlled, double-blind phase II study is to investigate if oral vitamin C may change the biology of low-risk myeloid malignancies; i.e., clonal cytopenia of undetermined significance (CCUS), low-risk myelodysplastic syndromes (MDS), and chronic myelomonocytic leukemia (CMML)-0/1 by reversing the epigenetic changes characteristic of these disease entities. The epigenetic regulator TET2 is the gene most often affected in CCUS. Preclinical studies have shown that active demethylation by the TET enzymes is dependent on vitamin C, and the investigators and collaborators have shown that plasma vitamin C levels are exceedingly low in hematological cancer patients but are easily corrected by oral vitamin C. This study is part of an array of EVITA studies aimed at clarifying whether the standard of care of patients with myeloid malignancies should be changed and oral vitamin C supplement added to the treatment recommendations.

Who can participate

Age range18 Years

SexALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Inclusion Criteria: A diagnosis of CCUS: * Persistent cytopenia for \> 6 months defined as hgb \< 11.3 g/dL (7 mmol/L) in women and hgb \< 12.9 g/dL (8 mmol/L) in men, thrombocyte count \< 150 x 10\^9/L or neutrophil count \< 1.8 x 10\^9/L * Normal cytogenetics (with the exception of deletion of the Y chromosome which can be accepted) * A bone marrow morphology that is not diagnostic of MDS or any other malignancy * Other common causes of cytopenia (vitamin or other deficiencies, virus infection, etc.) have been ruled out * Hematolytic conditions have been ruled out * The presence of a detectable mutation in genes recurrently affected in myeloid malignancy representing a clonal marker (excluding germline mutations) OR A diagnosis of MDS as according to World Health Organization (WHO) 2016 diagnostic criteria • Revised international prognostic scoring system (IPSS-R) risk score ≤ 3 AND bone marrow blast percentage \< 5 defining low-risk OR A diagnosis of CMML-0 or -1 as according to WHO 2016 diagnostic criteria AND (All diagnostic categories) The presence of a detectable mutation in genes recurrently affected in myeloid malignancy representing a clonal marker (excluding germline mutations) Exclusion Criteria: * Unwillingness to discontinue any and all use of vitamin C medication/supplementation including multivitamin at least 24 hours prior to Baseline investigations and sampling * Lack of ability to understand the information given, or lack of willingness to sign a…

What they're measuring

Median Change from Baseline in Variant Allele Frequency at 12 Months

Timeframe: At baseline and at 12 months

Trial details

NCT IDNCT03682029

SponsorRigshospitalet, Denmark

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2023-09-27