Recruiting
Phase 1

Ascorbate with Azacitidine & Venetoclax

Sponsor:

Kittika Poonsombudlert

Code:

NCT07177079

Conditions

Acute Myeloid Leukemia

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Azacitidine

Venetoclax

High-dose ascorbate

Decitabine

Study Details

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

Study ID

NCT07177079

Start date

Mar 18, 2026

Status verified date

Aug, 2026

Completion date

Dec 31, 2029

Anticipated

Primary completion date

Dec 31, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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%)
  • Calculated Creatinine clearance 25 - 45 mL/min using the Cockcroft-Gault formula
  • 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
  • Newly diagnosed (non-APL) acute myeloid leukemia except those with cytogenetic/molecular abnormalities in the exclusion criteria
  • 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 with evidence of Central Nervous System (CNS) disease involvement or who are at high risk of developing CNS disease at baseline/screening (defined as: presenting WBC > 200k/mm3, or monocytic differentiation or active CSN symptoms concerning CNS involvement per the treating physician) are eligible for this trial and may continue to receive or initiate intrathecal chemotherapy as treatment or prophylaxis, respectively, per institutional practice

Exclusion Criteria

  • 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
  • Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen
  • Other major co-morbidities as determined unsuitable per the treating physician
  • HIV-infection that is uncontrolled by anti-retroviral therapy. (HIV-infected patients on effective anti- retroviral therapy with undetectable viral load within 6 months are eligible for this study)
  • Patients with G6PD (glucose-6-phosphate dehydrogenase) deficiency
  • Patients who are on warfarin or other strong CYP3A4 inducer/inhibitor and cannot have a drug substitution or who decline the drug substitution

Study Design

Enrollment

30 participants

Anticipated

Allocation

Randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: A. Standard of Care (azacitidine and venetoclax)

Twelve patients will be randomized to Arm A.

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

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.

Interventions

Azacitidine

A chemotherapy drug known as a hypomethylating agent

Venetoclax

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.

High-dose ascorbate

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.

Decitabine

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.

Primary outcome measure

  • Phase I: Dose-limiting toxicities (DLTs) according to CTCAE version 5.0 [ Time Frame: Days 1 through 28 ]
  • Expansion: Composite complete remission rate defined as the proportion of patients with a complete remission (CR or CRi) [ Time Frame: Three years from initiation of study ]

Central Contacts and Locations

Central contacts

Kittika Poonsombudlert, MD

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

Locations

University of Iowa Health Care

Recruiting

Iowa City, Iowa, United States, 52242

Contacts

Kittika Poonsombudlert, MD

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

Kittika Poonsombudlert

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

More Information

Sponsor

Kittika Poonsombudlert

Last update posted

Aug 31, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Kittika Poonsombudlert on 2026-08-31.