NCT03397173

TET2 Mutations in Myelodysplastic Syndromes and Acute Myeloid Leukemia With Azacitidine + Ascorbic Acid

Targeting TET2 Mutations in Myelodysplastic Syndromes and Acute Myeloid Leukemia (AML) With Azacitidine and Ascorbic Acid

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 12 (actual)
• Sponsor: Case Comprehensive Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The purpose of this study is to evaluate the efficacy of treatment with azacitidine (an FDA approved drug for the treatment of MDS) and high dose ascorbic acid in patients with TET2 mutations. This approach is intended to enhance the enzymatic activity of TET2 protein, which in term may help to improve counts and symptoms, related to Myelodysplastic Syndromes and Acute Myeloid Leukemia. This combination is specific to individuals who carry this mutation.

Detailed description

Primary Endpoint To estimate the overall response rate (ORR) of the combination of standard dose azacitidine and oral dose of ascorbic acid in patients with MDS, AML, and MDS / Myeloproliferative Neoplasm (MPN) overlap with heterozygous TET2 mutations Secondary Endpoints 1. The safety profile of the combination in the targeted patient population 2. Response duration 3. Overall survival of the treated population (compared to matched historical cohort of patients treated with single agent Azacitidine) 4. The identification of biomarkers that predict response to the combination Study Design This is an open-label, phase II study that will be conducted at Cleveland Clinic, Taussig Cancer Institute. Azacitidine will be administered intravenously or subcutaneously at a fixed dose of 75mg/m2/day for 7 consecutive days, (allowing for weekends, and holidays) of each 28-day cycle. Ascorbic acid will be administered orally daily at 1 g/day three days prior to start azacitidine and then continues daily for a total of 28 days of each 28 day cycle.

Conditions

• Myelodysplastic Syndromes
• Myeloproliferative Neoplasm
• Acute Myeloid Leukemia

Interventions

Type	Name	Description
DRUG	Azacitidine	Azacitidine will be administered intravenously or subcutaneously at a fixed dose of 75mg/m2/day for 7 consecutive days, allowing interruptions for weekends and holidays within each 28-day cycle. No dose modifications will be permitted during the treatment period.
DRUG	Ascorbic acid	Ascorbic acid will be administered orally daily at 1 g/day three days prior to start azacitidine and then continues daily for a total of 28 days of each 28 day cycle. No dose modifications will be permitted during the treatment period.

Timeline

• Start date: 2018-03-16
• Primary completion: 2021-01-03
• Completion: 2021-01-21
• First posted: 2018-01-11
• Last updated: 2021-08-11

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study