A Phase Ib Study Evaluating the Safety and Tolerability of Vitamin C in Patients With Intermediate or High Risk Myelodysplastic Syndrome With TET2 Mutations
Overview
- Phase
- Phase 1
- Intervention
- Vitamin C
- Conditions
- Myelodysplastic Syndromes
- Sponsor
- NYU Langone Health
- Enrollment
- 4
- Locations
- 2
- Primary Endpoint
- Number of Patients Who Experienced a Dose Limiting Toxicity (DLT)
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is an open label, Phase Ib study designed to evaluate the safety, toxicity and biological activity of high dose Vitamin C in bone marrow and peripheral blood when administered as therapy to patients with intermediate or high risk myelodysplastic syndrome according to the revised IPSS (international prognostic scoring system) criteria whose disease has a Ten-eleven translocation-2, (TET2) mutation. The primary objectives phase 1 study is to establish safety and confirm a steady level of Vitamin C on ≥1 mM in > 75% of the patients is achieved. All patients will receive at least 1 cycle of treatment (4 weeks). Patients with clinical benefit (CR,PR, or SD) then will undergo a second 4-week cycle of treatment.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age ≥18 years
- •Histologically confirmed Myelodysplastic Syndrome with positive TET2 mutations (We will test all MDS patients for TET2 mutations using next generation sequencing and only patients with TET2 mutations will be included in our study)
- •Myeloblasts account for less than 20% of leukocytes on peripheral blood and bone marrow aspirate
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (Appendix 1)
- •Adequate organ function
- •Platelets ≥20,000/μL
- •Absolute neutrophil count ≥ 500/μL
- •Bilirubin \< 1.5 x institutional upper limit of normal (ULN) or \< 3 x ULN in patients with Gilbert's disease or liver involvement
- •Serum albumin ≥ 2.0 g/dL
- •Aspartate aminotransferase (AST)/Alanine aminotransferase (ALT) ≤2.5 institutional ULN or, in the case of liver involvement by the primary disease AST/ALT ≤ 5 x ULN
Exclusion Criteria
- •Concurrent hypomethylation agent usage; the last dose of treatment must be ≥4 weeks before the start of the Vitamin C infusion
- •Myeloblast count ≥20% in peripheral blood or bone marrow aspirate
- •Major surgery within 2 weeks prior to first dose of study drug
- •Allogeneic stem cell transplant
- •Any previous chemotherapy agent other than hypomethylating agents (e.g., Venetoclax)
- •Uncontrolled concurrent serious illness
- •Concurrent malignancy or history of a previous malignancy within 1 year prior to first dose of the current study, unless curatively resected basal, squamous cell carcinoma of the skin, breast ductal/lobular carcinoma in situ or cervical carcinoma in situ.
- •Active infections including hepatitis B carrier status, hepatitis C virus (HCV) infection (patients must have a negative Hep B and Hep C viral load at screening)
- •Known HIV-positive status
- •Any significant medical conditions, laboratory abnormality, or psychiatric illness that would exclude the subject from participation or interfere with study treatment, monitoring and compliance such as:
Arms & Interventions
Vitamin C 50 g
Patients will receive Vitamin C as a continuous intravenous infusion (CIVI) of 50 grams (g) daily over 24 hours for 5 days for total of 250 grams over 5 days up.
Intervention: Vitamin C
Vitamin C 75 g
Patients will receive Vitamin C as a continuous intravenous infusion (CIVI) of 75 grams (g) daily over 24 hours for 5 days for total of 375 grams over 5 days.
Intervention: Vitamin C
Vitamin C 100 g
Patients will receive Vitamin C as a continuous intravenous infusion (CIVI) of 100 grams (g) daily over 24 hours for 5 days for total of 500 grams over 5 days.
Intervention: Vitamin C
Outcomes
Primary Outcomes
Number of Patients Who Experienced a Dose Limiting Toxicity (DLT)
Time Frame: Week 16
DLT is defined as grade 3 or higher of any duration or as a Grade ≥2 adverse event (AE) that persists for ≥96 hours with the exception of Grade ≥ 2 AEs clearly related to the underlying MDS