Myelodysplastic SyndromesPhase 1/2NCT03433781
A Phase Ib Study Evaluating the Safety and Tolerability of Vitamin C in Patients With Intermediate or High Risk Myelodysplastic Syndrome With TET2 Mutations
A Phase 1/2 study testing Vitamin C in people with Myelodysplastic Syndromes, run by NYU Langone Health at 2 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndromes
- What is being tested?
- Vitamin C
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 May 2018to 16 May 2023
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
- Creatinine≤1.5 x institutional ULN or estimated creatinine clearance of ≥45 mL/min by the Cockcroft-Gault equation or measured creatinine clearance >45 mL/min
- Females of child bearing potential must have a negative serum pregnancy test with 7 days prior to first dose of treatment and use 2 methods of contraceptives while on treatment
- Ability to understand and the willingness to sign a written informed consent document
- Patients currently receiving or who previously received Hydroxyurea, Erythrocyte stimulating agents (ESA), or granulocyte colony stimulating factors (G-CSF) are allowed to participate in the study.
Who cannot join
- 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
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- 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:
- Unstable angina pectoris, symptomatic congestive heart failure (NYHA III or IV), myocardial infarction ≤ 6 months prior to first study drug, clinically significant and uncontrolled cardiac arrhythmia (e.g. atrial fibrillation/flutter ventricular cardiovascular physiology is allowed), cerebrovascular accidents ≤ 6 months before study drug start
- Severely impaired lung function
- Serious, systemic infection requiring treatment ≤7 days before the first dose of study drug
- Any severe, uncontrolled disease or condition which in the investigator's opinion, may put the subject at significant risk, may confound the study results, or impact the subject's participation in the study
- History of any renal calculi or hyperoxaluria or any other preexisting renal disorder
- History of G6PD deficiency, hereditary spherocytosis or hemochromatosis
- Patients on therapeutic or prophylactic anticoagulation will be excluded from enrollment on the protocol. However, patients can remain on the study if they develop a thrombosis that requires therapeutic anticoagulation during the course of protocol therapy
- Uncontrolled hyponatremia, SIADH, hypokalemia, hyerpkalemia, hypomagnesemia or hypermagnesemia
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Miami Miller School of Medicine -Sylvester Cancer Center
Miami, Florida, 33136
New York University School of Medicine
New York, New York, 10016
About this study
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.
- Conditions
- Myelodysplastic Syndromes
- Being tested
- Vitamin C
- Keywords
- ASCORBIC ACID
- Medical subject headings
- Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin CDrug
Also called ascorbic acid, ascorbate
All patients will receive at least 1 cycle of treatment (4 weeks) of Vitamin C as a continuous intravenous infusion (CIVI). Patients with clinical benefit (CR, PR, or SD) then will undergo a second 4-week cycle of treatment. Patients to receive a maximum of 16 weeks of treatment (4 cycles). If a patient progress after receiving a cycle of treatment then the patient will be withdrawn from the study. Patients will be maintained on 1 gram oral Vitamin C daily from the end of the CIVI until the beginning of the next cycle (from day 6 till 28).
| Study group | Role | What they receive |
|---|---|---|
| Vitamin C 50 g | Experimental | 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. Receives: Drug: Vitamin C |
| Vitamin C 75 g | Experimental | 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. Receives: Drug: Vitamin C |
| Vitamin C 100 g | Experimental | 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. Receives: Drug: Vitamin C |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients Who Experienced a Dose Limiting Toxicity (DLT)
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
Measured: Week 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Feb 2018
- Study start1 May 2018
- Primary completion6 Nov 2022
- Study completion16 May 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- 3 dose-escalation cohorts in a 3+3 design. One subject at a time will be enrolled into the first cohort until the first dose level cohort is completed and all patients treated successfully for one cycle.
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- Perlmutter New York University Cancer Center
- Responsible party
- Sponsor
- Investigators
- Mohammad M Abdul Hay, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03433781
- Sponsor's protocol ID
- 17-00978
- Status last verified
- Feb 2024
- First submitted
- 8 Feb 2018
- Last updated
- 27 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Study Evaluating the Safety and Tolerability of Vitamin C in Patients With Intermediate or High Risk Myelodysplastic Syndrome With TET2 Mutations
- ClinicalTrials.gov ID
- NCT03433781
- Acronym / sponsor ID
- 17-00978
- Conditions
- Myelodysplastic Syndromes
- Keywords
- ASCORBIC ACID
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- Perlmutter New York University Cancer Center
- Study start
- 1 May 2018 (actual)
- Primary completion
- 6 Nov 2022 (actual)
- Study completion
- 16 May 2023 (actual)
- First posted
- 15 Feb 2018 (actual)
- Results
- Posted 27 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 3 dose-escalation cohorts in a 3+3 design. One subject at a time will be enrolled into the first cohort until the first dose level cohort is completed and all patients treated successfully for one cycle.
| Arm | Type | Receives |
|---|---|---|
| Vitamin C 50 g | Experimental | Drug: Vitamin CPatients 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. |
| Vitamin C 75 g | Experimental | Drug: Vitamin CPatients 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. |
| Vitamin C 100 g | Experimental | Drug: Vitamin CPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- 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
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vitamin CAlso: ascorbic acid, ascorbateAll patients will receive at least 1 cycle of treatment (4 weeks) of Vitamin C as a continuous intravenous infusion (CIVI). Patients with clinical benefit (CR, PR, or SD) then will undergo a second 4-week cycle of treatment. Patients to receive a maximum of 16 weeks of treatment (4 cycles). If a patient progress after receiving a cycle of treatment then the patient will be withdrawn from the study. Patients will be maintained on 1 gram oral Vitamin C daily from the end of the CIVI until the beginning of the next cycle (from day 6 till 28). | Drug | Vitamin C 100 g, Vitamin C 50 g, Vitamin C 75 g |
Primary outcome
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mohammad M Abdul Hay, MD principal investigator
NYU Langone Health
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Vitamin C in people with Myelodysplastic Syndromes, run by NYU Langone Health at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Patients Who Experienced a Dose Limiting Toxicity (DLT) (time frame: Week 16). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2024.