High-dose Ascorbate (HDA) in Combination With Standard of Care Azacitidine and Venetoclax in Acute Myeloid Leukemia (AML)

NCT07177079 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 202506290
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label, Phase I clinical study with expansion. It will assess the safety and efficacy of high-dose ascorbate administered concomitantly with azacitidine and venetoclax in newly diagnosed AML.

Conditions

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• Phase I: Dose-limiting toxicities (DLTs) according to CTCAE version 5.0

  As this is the first time high-dose ascorbate has been administered in combination with standard of care aza/ven, the safety of the combination will be assessed in the first 6 patients randomized to Arm B. An initial DLT assessment will be made when 3 participants have been randomized to the Investigational Arm B and are evaluable for DLTs. If at most 1 out of 3 participants experience a DLT, an additional cohort of 3 participants will be evaluated for DLTs. If at most 1 out of 6 participants experience a DLT, the combination will be deemed safe. Should greater than or equal to 2 (≥2) out of 3 or 6 participants experience a DLT, the combination will be deemed unsafe, and accrual will be terminated.

  Days 1 through 28

• Expansion: Composite complete remission rate defined as the proportion of patients with a complete remission (CR or CRi)

  The primary objective of the expansion is to estimate the composite complete remission rate defined as the proportion of patients with a complete remission (CR or CRi) by the end of study treatment for each arm separately.

  Three years from initiation of study

Study Arms (2)

A. Standard of Care (azacitidine and venetoclax)

ACTIVE COMPARATOR

Twelve patients will be randomized to Arm A.

Drug: Azacitidine; Drug: Venetoclax; Drug: Decitabine

B. High-dose ascorbate administered concomitantly with azacitidine and venetoclax

EXPERIMENTAL

As this is the first time high-dose ascorbate has been administered in combination with standard of care (azacitidine and venetoclax), the safety of the combination will be assessed in the first 6 patients randomized to Arm B. These patients will continue with the expansion portion of the study, and an additional 6 patients will be added for a total of 12.

Drug: Azacitidine; Drug: Venetoclax; Drug: High-dose ascorbate; Drug: Decitabine

Interventions

Azacitidine DRUG

A chemotherapy drug known as a hypomethylating agent

A. Standard of Care (azacitidine and venetoclax); B. High-dose ascorbate administered concomitantly with azacitidine and venetoclax

Venetoclax DRUG

Targeted cancer therapy used to treat certain blood cancers. It specifically targets a protein called BCL-2 to trigger the self-destruction of cancer cells.

A. Standard of Care (azacitidine and venetoclax); B. High-dose ascorbate administered concomitantly with azacitidine and venetoclax

High-dose ascorbate DRUG

Administering vitamin C intravenously to achieve very high concentrations in the bloodstream. In contrast to low doses, which act as antioxidants, these pharmacological doses can function as a pro-oxidant, killing cancer cells while leaving healthy cells unharmed.

Also known as: Vitamin C

B. High-dose ascorbate administered concomitantly with azacitidine and venetoclax

Decitabine DRUG

Azacitidine may be substituted with decitabine 20 mg/m2 daily, on days 1-5, at PI discretion in the event of toxicity/drug supply shortage.

A. Standard of Care (azacitidine and venetoclax); B. High-dose ascorbate administered concomitantly with azacitidine and venetoclax

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged ≥ 18 who are deemed unfit for intensive chemotherapy by meeting at least one of the following criteria:
• age ≥ 75
• Eastern Cooperative Oncology Group (ECOG) performance of 2-3
• Severe cardiac disorder (e.g., congestive heart failure requiring treatment, ejection fraction ≤ 50%, or chronic stable angina)
• Severe pulmonary disorder (e.g., DLCO ≤ 65% or FEV1 ≤ 65%)
• Creatinine clearance \< 45 mL/min
• Hepatic disorder with total bilirubin \> 1.5 times the upper limit of normal
• Any other comorbidity that the investigators determine to be incompatible with intensive chemotherapy

You may not qualify if:

• Participants must have adequate organ function, defined as:
• Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3.0 x upper limit of normal (ULN)
• International normalized ratio (INR) \< 1.5 x ULN and partial thromboplastin time (PTT) \< 1.5 x ULN (patient could be eligible if they respond appropriately to correction with FFP or cryoprecipitate)
• Patients with a history of antecedent myelodysplasia (MDS) are eligible if they have not had prior chemotherapy/hypomethylating agent (e.g., azacitidine or decitabine). Prior exposure to other investigational agents could be considered at PI's discretion
• Patients who have developed therapy-related AML after prior radiation or chemotherapy for other malignancy(ies) are eligible if they have not been exposed to hypomethylating agent (e.g., azacitidine or decitabine) and/or venetoclax
• Patients presenting with marked leukocytosis (WBC \> 25 k/mm3) should receive cytoreduction with hydroxyurea or cytarabine dose ≤ 1 g/m2 to mitigate the risk of tumor lysis syndrome before initiation of therapy with venetoclax
• For female participants of childbearing potential, a negative serum or urine pregnancy test (sensitivity of at least 25 mIU/mL) at screening
• Ability to understand and the willingness to sign a written informed consent document.
• Both male and female participants of childbearing potential agree to use an adequate method of contraception from screening through 6 months after the last dose of study treatment.
• Patients who have received prior therapy to treat their AML (except for cytoreductive hydroxyurea or cytarabine dose ≤ 1 g/m2 for hyperleukocytosis)
• Known hypersensitivity or allergy to ascorbate, azacitidine/decitabine, or venetoclax
• AML patients with the following cytogenetic/molecular aberrations are not eligible i. t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 ii. inv(16)(p13.1q22) or t(16;16)(p13.1;q22)/ CBFB::MYH11 iii. bZIP in-frame mutated CEBPA without any adverse mutations iv. KMT2A rearrangement v. NPM1 or IDH1 or IDH2 or FLT3-ITD or FLT3-TKD mutation
• Patients with kidney disease needing dialysis, diabetic nephropathy, renal transplant recipients, and those with history of acute or chronic oxalate nephropathy
• Patients with primary hemochromatosis or transfusional iron overload as defined as persistently elevated Ferritin \> 1000 ng/mL.
• Patients with type I or type II diabetes mellitus on treatment with short acting insulin who need at least a daily blood glucose monitoring test via finger stick

Sponsors & Collaborators

• Kittika Poonsombudlert: lead

Study Sites (1)

University of Iowa Health Care

Iowa City, Iowa, 52242, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

Azacitidine; venetoclax; Ascorbic Acid; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Sugar Acids; Acids, Acyclic; Carboxylic Acids; Hydroxy Acids; Carbohydrates

Study Officials

• Kittika Poonsombudlert, MD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kittika Poonsombudlert, MD

CONTACT

+1 319 356 1770; kittika-poonsombudlert@uiowa.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: September 9, 2025
• First Posted: September 16, 2025
• Study Start: March 18, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2029
• Last Updated: April 9, 2026

Record last verified: 2026-03

Locations

US (1)