Combining Active and Passive DNA Hypomethylation

  • STATUS
    Recruiting
  • End date
    Mar 8, 2024
  • participants needed
    196
  • sponsor
    Kirsten Grønbæk
Updated on 8 October 2021
cancer
stem cell transplantation
myeloproliferative disorder
chronic myelomonocytic leukemia
cell transplantation
azacitidine
blast cells
cmml-2
therapy-related mds

Summary

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.

Description

EVI-3 is a phase 2 international, multicentre, randomized, parallel-group, placebo-controlled, double-blind study of the efficacy and safety of oral vitamin C supplement in combination with azacitidine (AZA) in patients with higher-risk myeloid malignancies with or without mutations in genes recurrently affected in myeloid malignancies. Treatment allocation is in 1:1 ratio (vitamin C vs. placebo) by block randomization stratified by clinical site. Study entry is staggered. Patients are randomized to either oral vitamin C 1000 mg daily or placebo from start of AZA treatment until end of study (EOS) or until AZA treatment is discontinued at the discretion of the treating physician, whichever occurs earlier. The accrual time is estimated to 48 months and 6 months follow-up, thus, maximum treatment duration will be approximately 54 months. A total of 196 patients is planned for enrollment.

Study visits are scheduled at baseline, after 1st AZA treatment cycle, after 6 AZA treatment cycles, and, if AZA treatment is continued, at EOS or end of AZA treatment. Evaluations at study visits include bone marrow investigation, peripheral blood tests, patient-reported outcome measures, adverse events and compliance. Bone marrow aspirate and peripheral blood will be collected for biobank at each study visit.

All patients will undergo follow-up once yearly from EOS. Follow-up will include information on duration of AZA therapy, survival and disease progression from myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) to acute myeloid leukemia (AML), if diagnosed following a clinical indication for a bone marrow test.

Details
Condition MYELODYSPLASTIC SYNDROME, myelodysplastic syndrome (mds), myelodysplastic syndromes, chronic myelomonocytic leukaemia, Acute myeloid leukemia, Myelodysplastic Syndromes (MDS), Bone Marrow Disorder, Acute Myeloid Leukemia, Chronic myelomonocytic leukemia, Juvenile Myelomonocytic Leukemia, acute myelogenous leukemia, anll, cmml, Acute Myelogenous Leukemia (AML), Bone marrow disorder, Preleukemia, acute myeloblastic leukemia
Treatment Placebo, Vitamin C
Clinical Study IdentifierNCT03999723
SponsorKirsten Grønbæk
Last Modified on8 October 2021

Eligibility

Yes No Not Sure

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

Patients eligible for allogeneic stem cell transplantation
Prior therapy with hypomethylating agents
Any matter constituting an exclusion criterion for treatment with azacitidine
Patients receiving other active cancer treatment, including investigational agents, with the exception of hydroxyurea for white blood cell control and granulocyte colony-stimulating factor
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
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