Recruiting
Phase 2

HMA vs. Induction

Sponsor:

The Methodist Hospital Research Institute

Code:

NCT07060001

Conditions

Acute Myeloid Leukemia (AML)

Acute Myeloid Leukaemia (AML)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

5hmC Biomarker

Venetoclax

Decitabine 20 mg/m²/day for 5 days

Azacitidine (AZA)

Cytarabine (Ara-C)

Study Details

Brief summary:

This is a therapeutic intervention trial evaluating the clinical utility of a novel blood-based epigenetic biomarker-genome-wide 5-hydroxymethylcytosine (5hmC) in cell-free DNA (cfDNA)-for assessing measurable residual disease (MRD) in patients with newly diagnosed acute myeloid leukemia (AML). The study compares the efficacy of hypomethylating agent (HMA)-based therapy versus intensive induction chemotherapy, using the 5hmC biomarker to guide post-induction treatment decisions. Approximately 112 adult patients will be enrolled and assigned to treatment arms based on a stratified sampling scheme. Blood samples will be collected at defined intervals to assess MRD status. Primary endpoints include minimal residual disease (MRD) negativity rate, duration of remission, event-free survival (EFS), and overall survival (OS).

Conditions

Acute Myeloid Leukemia (AML)

Acute Myeloid Leukaemia (AML)

Study ID

NCT07060001

Start date

Apr 9, 2026

Status verified date

Mar, 2026

Completion date

Dec, 2029

Anticipated

Primary completion date

Dec, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

1. The patient (or legally acceptable representative if applicable) provides written informed consent for the trial. Spanish speaking patients will be included and translation services will be provided as needed.
2. Male or female, 18 years of age or older, on the day of informed consent signing.
3. Newly diagnosed de novo AML

5\. Expected life expectancy of at least 6 months 6. Willing and able to comply with the protocol for the duration of the trial including undergoing treatment and scheduled visits and examinations. 7. Women with childbearing potential and men should practice at least one of the following methods of birth control throughout the study and for 6 for women and 3 months for men after the last dose of study therapy:

1. Total abstinence from sexual intercourse (periodic abstinence not acceptable);
2. Surgically sterile partner(s) including vasectomy, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy;
3. Practicing 2 effective methods of contraception (at least 1 highly effective, method of contraception \[See Appendix 4\]). WOCBP should only be included after a confirmed negative serum pregnancy test.

Exclusion Criteria:

1. Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 3 weeks of trial treatment administration.
2. The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study
3. Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
4. Confirmed positive pregnancy test in WOCBP.

Study Design

Enrollment

112 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: HMA- Based Treatment Arm

Azacitidine or Decitabine with or without Venetoclax (HMA-based treatment):

  • Venetoclax is a BCL-2 inhibitor FDA Approved for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy, in combination with azacitidine, decitabine or low-dose cytarabine in.
  • Decitabine is a nucleoside metabolic inhibitor that is administered as an intravenous infusion over a 1-3 hours.
  • Azacitidine can be given as a sub-cutaneous injection or intravenously. In AML, the most common adverse reactions (≥30%) in combination with azacitidine or decitabine or low-dose cytarabine were nausea, diarrhea, thrombocytopenia, constipation, neutropenia, febrile neutropenia, fatigue, vomiting, peripheral edema, pyrexia, pneumonia, dyspnea, hemorrhage, anemia, rash, abdominal pain, sepsis, back pain, myalgia, dizziness, cough, oropharyngeal pain, and hypotension.

active comparator: Intensive Chemotherapy Arm

Cytarabine with Anthracycline (standard intensive induction therapy):

  • Cytarabine is FDA approved chemotherapy (pyrimidine analog) infusion that is frequently used with other drug such as anthracycline to treat acute myeloid leukemia, acute lymphoblastic leukemia. Common side effects include low counts, immune suppression, nausea, neutropenic fever.
  • Anthracyclines are chemotherapy infusions which topoisomerase II inhibition. Other than having side effects similar to cytarabine, it may cause weakening of heart pumping function few years later. Both of these medications may cause a temporary loss of hair in some people. After treatment with cytarabine has ended, normal hair growth should return.

Interventions

5hmC Biomarker

The 5hmC marker will be used to determine treatment modality post-induction therapy. After Week 4 of standard-of-care therapy (either HMA-based treatment or intensive induction chemotherapy), 5hmC biomarker testing will be performed. If MRD is positive, patients will continue the same standard-of-care treatment or crossover to the other arm of the study. If MRD is negative, patients will proceed with consolidation (either HSCT or continue on same treatment). For patients receiving HMA-based treatment, blood samples will be collected ± 5 days before and after 4 and 12 weeks of therapy. For patients receiving intensive chemotherapy blood samples will be collected ± 5 days before and after 4 and 12 weeks of therapy.

Venetoclax

Venetoclax is a BCL-2 inhibitor FDA Approved for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy, in combination with azacitidine, decitabine or low-dose cytarabine.

Decitabine 20 mg/m²/day for 5 days

Decitabine is a nucleoside metabolic inhibitor that is administered as an intravenous infusion over a 1-3 hours.

Azacitidine (AZA)

Azacitidine can be given as a sub-cutaneous injection or intravenously.

Cytarabine (Ara-C)

Cytarabine is FDA approved chemotherapy (pyrimidine analog) infusion that is frequently used with other drug such as anthracycline to treat acute myeloid leukemia, acute lymphoblastic leukemia. Common side effects include low counts, immune suppression, nausea, neutropenic fever.

Anthracycline

Anthracyclines are chemotherapy infusions which topoisomerase II inhibition. Other than having side effects similar to cytarabine, it may cause weakening of heart pumping function few years later. Both of these medications may cause a temporary loss of hair in some people. After treatment with cytarabine has ended, normal hair growth should return.

Primary outcome measure

  • 5hmC Minimal Residual Disease Rates [ Time Frame: From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 30 months. ]
  • Duration of Remission (DoR) Based on 5hmC-MRD Status [ Time Frame: From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 30 months. ]
  • Event-Free Survival (EFS) by 5hmC-MRD Status [ Time Frame: From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 30 months. ]
  • Overall Survival (OS) in Relation to 5hmC-MRD [ Time Frame: From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 30 months. ]

Central Contacts and Locations

Central contacts

Danielle Sewell

3462382674dmsewall@houstonmethodist.org

Titilayo Olubajo

7133639803tolubajo@houstonmethodist.org

Locations

Houston Methodist Neal Cancer Center

Recruiting

Houston, Texas, United States, 77030

Contacts

Shilpan Shah, MD

713-441-9948sshah2@houstonmethodist.org

Siddhartha Ganguly, MD

sganguly@houstonmethodist.org

More Information

Sponsor

The Methodist Hospital Research Institute

Last update posted

Oct 8, 2026

Last verified

Mar, 2026

Keywords

  • AML
  • Leukemia
  • Acute Myeloid Leukemia

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-09. This information was provided to ClinicalTrials.gov by The Methodist Hospital Research Institute on 2026-10-08. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.