Combining Active and Passive DNA Hypomethylation
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorKirsten Grønbæk
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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)
Disqualifiers
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
Trial design
Design model
Parallel
Treatments tested in this trial
Vitamin C
Dietary supplementOral vitamin C (ascorbic acid) 1000 mg daily will be administered from day 1 in the 1st AZA cycle (D1/C1) and continued until discontinuation of AZA or EOS as combination treatment.
Placebo
Dietary supplementPlacebo capsules (two capsules once daily) will be administered from day 1 in the 1st AZA cycle (D1/C1) and continued until discontinuation of AZA or EOS.
Treatment groups
196 Participants
are divided into 2 treatment groupsGroup A: Vitamin CExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Event-free survival
Event-free survival in months in the group of patients receiving oral vitamin C + AZA (arm A) vs. the group of patients receiving placebo + AZA (arm B) calculated from the time of randomization to EOS. Event is defined as death, relapse, progression or lack of a response at 6 AZA cycles as defined by IWG 2006 (MDS and CMML) and ELN 2017 (AML) response criteria
Time frame
0-54 monthsSecondary outcomes
1
Adverse events and serious adverse events
Number and ratio of patients with adverse events in arm A vs. arm B assessed from the time of administration of intervention (day 1, AZA cycle 1 = D1/C1) to EOS. Total number of adverse events and serious adverse events and the number per year from D1/C1 to EOS in arm A vs. arm B. Number of patients discontinuing the intervention and discontinuation rate in arm A vs. arm B from D1/C1 to EOS
Time frame
0-54 months2
Overall survival
Overall survival in months in arm A vs. arm B calculated from the time of randomization to EOS
Time frame
0-54 months3
Overall response rate
Rate of overall response and rates of individual responses (as according to international consensus criteria), including best response, in arm A vs. arm B after 6 AZA cycles and at EOS
Time frame
0-54 months4
Patient-reported outcome (PRO) measures
Change in PRO measures including health-related quality of life scores (EORTC QLQ-C30 and Hematological Malignancy (HM)-PRO) from baseline to end of 1st AZA cycle, after 6 AZA cycles and EOS, if AZA treatment ongoing, respectively, in arm A vs. arm B. Numerical PRO scores after the 1st AZA cycle and after 6 AZA cycles (and EOS), respectively, in arm A vs. arm B
Time frame
0-54 monthsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Kirsten Grønbæk
Lead sponsor
Rigshospitalet, Denmark
Sponsor institution
Van Andel Institute - Stand Up To Cancer Epigenetics Dream Team
Collaborator
Karolinska University Hospital
Collaborator
Skane University Hospital
Collaborator
Sahlgrenska University Hospital
Collaborator
University of Southern California
Collaborator
Imperial College London
Collaborator
University of Copenhagen
Collaborator
Zealand University Hospital
Collaborator
Aalborg University Hospital
Collaborator
Odense University Hospital
Collaborator
Technical University of Denmark
Collaborator
Aarhus University Hospital
Collaborator
Uppsala University Hospital
Collaborator
Source ClinicalTrials.gov