Skip to main content

Azacitidine and Ascorbic Acid in Treating Patients with TET2-Mutated Newly Diagnosed, Recurrent, or Refractory Blood Cancer

Trial Status: Active

This phase II trial studies how well azacitidine and ascorbic acid work in treating patients with TET2-mutated blood cancer that is newly diagnosed, has come back, or does not respond to treatment. Drugs used in chemotherapy, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving azacitidine and ascorbic acid may help to enhance the enzymatic activity of TET2 protein, which may in tern help to improve the counts and symptoms related to the disease.

Inclusion Criteria

  • Patients must have a confirmed heterozygous TET2 mutations identified by next generation targeted deep sequencing
  • Patients must have MDS, or MDS/MPN overlap defined by 2016 World Health Organization (WHO) criteria; both newly diagnosed or previously treated MDS or MDS/MPN patients are eligible as long as the patient has never received prior treatment with azacitidine or decitabine
  • Patients with leukemic/blast phase transformation MPN
  • Patient with AML according to 2016 WHO criteria (excluding acute promyelocytic leukemia [APL] [AML-M3])
  • Newly diagnosed patients who are ineligible or declined to receive intensive chemotherapy after discussion of risks and benefits of that approach or patients with primary refractory/relapsed AML
  • Patients with active central nervous system (CNS) leukemia eligible at the discretion of treating physician
  • Relapse/refractory is defined as at least 1 course of treatment for AML excluding any patients treated with azacitidine or decitabine
  • Patients should be off any prior treatment or line of therapy for 2 weeks prior to start study with the exception of hydrea (hydroxyurea)
  • Prior therapy with hydroxyurea, biological or targeted therapy (e.g. flt3 inhibitors, other kinase inhibitors) or hematopoietic growth factors is allowed
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 3
  • Patients must have normal organ and marrow function as defined at the discretion of the treating physician and principal investigator (PI)
  • Women of childbearing potential must have a negative serum or urine pregnancy test within 10-14 days prior to enrollment
  • Patients must have the ability to understand and the willingness to sign a written informed consent document
  • Patient must be willing to comply with all aspects of the protocol including completing the drug diary
  • Patient must discontinue any and all use of multivitamin and/or vitamin c medication 24 hours before first dose of ascorbic acid

Exclusion Criteria

  • Any prior treatment with azacitidine or decitabine
  • Patients diagnosed with APL, AML-M3
  • Patients receiving other active treatment for their myeloid malignancy including investigational agents with the exception of hydrea for white blood cell (WBC) control
  • Nursing or pregnant women
  • History of allergic reactions to either azacitidine or ascorbic acid
  • Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • Patients with higher risk of bleeding (deemed by the treating physician) or on anticoagulation
  • Patients who are unwilling or unable to comply with all study requirements


Case Comprehensive Cancer Center
Status: ACTIVE
Contact: Aziz Nazha
Phone: 216-445-0320


I. To estimate the overall response rate (ORR) of the combination of standard dose azacitidine and ascorbic acid in patients with myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and MDS/myeloproliferative neoplasm (MPN) overlap with heterozygous TET2 mutations.


I. The safety profile of the combination of azacitidine and ascorbic acid in the targeted patient population.

II. The response duration for study patients.

III. The overall survival of the treated population (compared to matched historical cohort of patients treated with single agent azacitidine).

IV. The identification of genomic biomarkers that may predict response to the combination treatment.

V. Evaluation of changes in methylation prior and during therapy.


Patients receive ascorbic acid orally (PO) once daily (QD). After 3 days, patients also receive azacitidine intravenously (IV) over 10-40 minutes or subcutaneously (SC) on days 1-7. Courses repeat every 28 days in the absence of disease progression or unaccepted toxicity.

After completion of study treatment, patients are followed up bimonthly for 1 year.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Case Comprehensive Cancer Center

Principal Investigator
Aziz Nazha

  • Primary ID CASE1917
  • Secondary IDs NCI-2018-00235
  • ID NCT03397173