RecruitingPhase 2NCT03999723

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

Sponsor

Kirsten Grønbæk

Enrollment

196 participants

Start Date

Sep 11, 2019

Study Type

INTERVENTIONAL

Conditions

Acute Myeloid Leukemia Myelodysplastic Syndromes Chronic Myelomonocytic Leukemia

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria5

• 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 Criteria13

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)

Interventions

DIETARY_SUPPLEMENTVitamin C

Oral 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.

DIETARY_SUPPLEMENTPlacebo

Placebo 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.