Acute Myeloid Leukemia (AML)Phase 2NCT07060001
Efficacy of Hypomethylating Agents vs. Intensive Chemotherapy in Acute Myeloid Leukemia Using 5hmC as a Blood-Based Minimal Residual Disease Marker
A Phase 2 study testing 5hmC Biomarker, Venetoclax and Decitabine 20 mg/m²/day for 5 days in people with Acute Myeloid Leukemia (AML) and Acute Myeloid Leukaemia (AML), run by The Methodist Hospital Research Institute at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Myeloid Leukemia (AML), Acute Myeloid Leukaemia (AML)
- What is being tested?
- 5hmC Biomarker, Venetoclax and Decitabine 20 mg/m²/day for 5 days
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 112 participants
- Where
- 1 siteUnited States
- Study dates
- 9 Apr 2026to Dec 2029
- Phase
- Phase 2
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
- 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.
- Male or female, 18 years of age or older, on the day of informed consent signing.
- 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:
- Total abstinence from sexual intercourse (periodic abstinence not acceptable);
- Surgically sterile partner(s) including vasectomy, bilateral tubal ligation, bilateral oophorectomy, or hysterectomy;
- 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.
Who cannot join
- 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.
- The patient has serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study
- Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
- Confirmed positive pregnancy test in WOCBP.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Houston Methodist Neal Cancer Center
Houston, Texas, 77030
Shilpan Shah, MD, 713-441-9948, sshah2@houstonmethodist.org
Siddhartha Ganguly, MD, sganguly@houstonmethodist.org
About this study
Official title: Evaluation of the Efficacy of Hypomethylating Agent Versus Standard Intensive Chemotherapy Induction Based on 5hmC - a Novel, Blood Epigenetic Marker for Assessing Measurable Residual Disease in Patients With Acute Myeloid Leukemia
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).
Read the detailed description
This is a therapeutic intervention trial evaluating the efficacy of a novel, blood epigenetic marker [genome-wide 5 hydroxymethylcytosine (5hmC) of cell free DNA (cfDNA)] for assessing measurable residual disease (MRD) in patients with acute myeloid leukemia (AML). Using the highly sensitive cfDNA 5hmC method, the trial will evaluate clinical efficacy of induction therapy and minimal residual disease (MRD) guided therapy in AML patients. Female or male patients aged 18 years, or older, with newly diagnosed de novo AML who will receive induction therapy with either hypomethylating agent (HMA) -based treatment or intensive chemotherapy will be eligible to participate in the trial. Patients will be assigned to one of the two treatment options based on a stratified sampling scheme. Approximately, 112 patients will be enrolled in the study. Informed consent will be obtained from all patients prior to participation.
The efficacy of HMA-based treatment versus intensive induction chemotherapy will be evaluated using the cfDNA 5hmC method in AML patients. 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. The primary endpoints will be assessment of cfDNA 5hmC-MRD negativity rate, duration of remission, event-free survival (EFS), and overall survival (OS) in the two treatment groups. EFS will be assessed from the time of treatment initiation to the first occurrence of disease progression (>5% blasts in blood or bone marrow) or death from any cause. All sample collections will be conducted in accordance with the patient's standard-of-care visits. Patient samples will be collected prospectively at Houston Methodist Hospital. At least 112 subjects will be enrolled.
The hypothesis is that the 5hmC method for MRD detection will be more sensitive in AML patients receiving HMA-based regimens compared with those receiving intensive induction chemotherapy.
- Being tested
- 5hmC Biomarker, Venetoclax, Decitabine 20 mg/m²/day for 5 days, Azacitidine (AZA), Cytarabine (Ara-C)
- Keywords
- AML, Leukemia, Acute Myeloid Leukemia
- Medical subject headings
- Leukemia, Myeloid, Acute, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5hmC BiomarkerDiagnostic test
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.
VenetoclaxDrug
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 daysDrug
Decitabine is a nucleoside metabolic inhibitor that is administered as an intravenous infusion over a 1-3 hours.
Azacitidine (AZA)Drug
Azacitidine can be given as a sub-cutaneous injection or intravenously.
Cytarabine (Ara-C)Drug
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.
AnthracyclineDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| HMA- Based Treatment Arm | Active comparator | 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. Receives: Diagnostic Test: 5hmC Biomarker; Drug: Venetoclax; Drug: Decitabine 20 mg/m²/day for 5 days; Drug: Azacitidine (AZA) |
| Intensive Chemotherapy Arm | Active comparator | 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. Receives: Diagnostic Test: 5hmC Biomarker; Drug: Cytarabine (Ara-C); Drug: Anthracycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
5hmC Minimal Residual Disease Rates
cfDNA 5hmC-MRD negativity and positivity rates at the time of morphologic remission.
Measured: 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 from initial treatment to disease relapse or progression, stratified by 5-hydroxymethylcytosine minimal residual disease (5hmC-MRD) status (positive vs. negative). This measure evaluates the impact of 5hmC-MRD on the sustainability of remission.
Measured: 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 from treatment initiation to the occurrence of any treatment failure event, including relapse, progression, or death from any cause, compared between patients with positive and negative 5hmC-MRD. This outcome assesses the prognostic value of 5hmC-MRD in predicting treatment durability.
Measured: 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 from diagnosis or treatment start to death from any cause, analyzed by 5hmC-MRD status. This outcome measure determines whether 5hmC-MRD positivity is associated with reduced overall survival.
Measured: From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 30 months.
Secondary outcomes (4)
MRD Positivity Rate Across Detection Methods
Proportion of patients identified as MRD-positive following induction therapy using 5hmC, multiparameter flow cytometry (MFC), RT-PCR, and next-generation sequencing (NGS). This outcome compares the sensitivity and concordance of MRD detection methods.
Measured: 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) in MRD-Positive and MRD-Negative Patients by Method
Time from initial treatment to relapse or progression, stratified by MRD status (positive vs. negative) as determined by 5hmC, MFC, RT-PCR, and NGS. This outcome evaluates the prognostic value of each method in predicting remission durability.
Measured: 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 by MRD Detection Method
Event-free survival (EFS) measured from treatment initiation, stratified by MRD status as determined by each method (5hmC, MFC, RT-PCR, NGS). This outcome assesses the predictive utility of each MRD method for long-term clinical outcomes.
Measured: 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 by MRD Detection Method
Overall survival (OS) measured from treatment initiation, stratified by MRD status as determined by each method (5hmC, MFC, RT-PCR, NGS). This outcome assesses the predictive utility of each MRD method for long-term clinical outcomes.
Measured: From date of initial treatment until progression, unacceptable toxicity, treating physician's discretion, or patient withdraws, whichever comes first, assessed up to 30 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2025
- Study start9 Apr 2026
- Primary completionDec 2028 (estimated)
- Study completionDec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (63)Papers the sponsor has linked to this study.
- Other trials for Acute Myeloid Leukemia (AML)Studies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 112 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Shilpan Shah, MD, Principal investigator, Houston Methodist Neal Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07060001
- Sponsor's protocol ID
- PRO00038056 (HMCC-HM24-001)
- Status last verified
- Mar 2026
- First submitted
- 20 Jun 2025
- Last updated
- 8 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified data sets regarding the correlation between minimal residual disease using the 5hmC biomarker and the type of standard of care treatment may be used by researchers at Houston Methodist and/or shared with other researchers, the government, and other institutions for use in future research.
Publications
Krug U, Rollig C, Koschmieder A, Heinecke A, Sauerland MC, Schaich M, Thiede C, Kramer M, Braess J, Spiekermann K, Haferlach T, Haferlach C, Koschmieder S, Rohde C, Serve H, Wormann B, Hiddemann W, Ehninger G, Berdel WE, Buchner T, Muller-Tidow C; German Acute Myeloid Leukaemia Cooperative Group; Study Alliance Leukemia Investigators. Complete remission and early death after intensive chemotherapy in patients aged 60 years or older with acute myeloid leukaemia: a web-based application for prediction of outcomes. Lancet. 2010 Dec 11;376(9757):2000-8. doi: 10.1016/S0140-6736(10)62105-8. Epub 2010 Dec 3.
PubMed 21131036Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE, Anderson JE, Petersdorf SH. Age and acute myeloid leukemia. Blood. 2006 May 1;107(9):3481-5. doi: 10.1182/blood-2005-09-3724. Epub 2006 Feb 2.
PubMed 16455952Camus V, Stamatoullas A, Mareschal S, Viailly PJ, Sarafan-Vasseur N, Bohers E, Dubois S, Picquenot JM, Ruminy P, Maingonnat C, Bertrand P, Cornic M, Tallon-Simon V, Becker S, Veresezan L, Frebourg T, Vera P, Bastard C, Tilly H, Jardin F. Detection and prognostic value of recurrent exportin 1 mutations in tumor and cell-free circulating DNA of patients with classical Hodgkin lymphoma. Haematologica. 2016 Sep;101(9):1094-101. doi: 10.3324/haematol.2016.145102. Epub 2016 Jun 13.
PubMed 27479820Armand P, Oki Y, Neuberg DS, Faham M, Cummings C, Klinger M, Weng L, Bhattar S, Lacasce AS, Jacobsen ED, Davids MS, Jacobson C, Fisher DC, Brown JR, Fowler NH, Alma Rodriguez M, Wallace MJ, Neelapu SS, Rodig S, Younes A, Freedman AS. Detection of circulating tumour DNA in patients with aggressive B-cell non-Hodgkin lymphoma. Br J Haematol. 2013 Oct;163(1):123-6. doi: 10.1111/bjh.12439. Epub 2013 Jun 25. No abstract available.
PubMed 23795711Cuccaro A, Bartolomei F, Cupelli E, Galli E, Giachelia M, Hohaus S. Prognostic factors in hodgkin lymphoma. Mediterr J Hematol Infect Dis. 2014 Jul 5;6(1):e2014053. doi: 10.4084/MJHID.2014.053. eCollection 2014.
PubMed 25045461Schwarz AK, Stanulla M, Cario G, Flohr T, Sutton R, Moricke A, Anker P, Stroun M, Welte K, Bartram CR, Schrappe M, Schrauder A. Quantification of free total plasma DNA and minimal residual disease detection in the plasma of children with acute lymphoblastic leukemia. Ann Hematol. 2009 Sep;88(9):897-905. doi: 10.1007/s00277-009-0698-6. Epub 2009 Jan 23.
PubMed 19165483Nakamura S, Yokoyama K, Shimizu E, Yusa N, Kondoh K, Ogawa M, Takei T, Kobayashi A, Ito M, Isobe M, Konuma T, Kato S, Kasajima R, Wada Y, Nagamura-Inoue T, Yamaguchi R, Takahashi S, Imoto S, Miyano S, Tojo A. Prognostic impact of circulating tumor DNA status post-allogeneic hematopoietic stem cell transplantation in AML and MDS. Blood. 2019 Jun 20;133(25):2682-2695. doi: 10.1182/blood-2018-10-880690. Epub 2019 Apr 1.
PubMed 30936070Bohers E, Viailly PJ, Dubois S, Bertrand P, Maingonnat C, Mareschal S, Ruminy P, Picquenot JM, Bastard C, Desmots F, Fest T, Leroy K, Tilly H, Jardin F. Somatic mutations of cell-free circulating DNA detected by next-generation sequencing reflect the genetic changes in both germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphomas at the time of diagnosis. Haematologica. 2015 Jul;100(7):e280-4. doi: 10.3324/haematol.2015.123612. Epub 2015 Mar 6. No abstract available.
PubMed 25749829Yeh P, Dickinson M, Ftouni S, Hunter T, Sinha D, Wong SQ, Agarwal R, Vedururu R, Doig K, Fong CY, Blombery P, Westerman D, Dawson MA, Dawson SJ. Molecular disease monitoring using circulating tumor DNA in myelodysplastic syndromes. Blood. 2017 Mar 23;129(12):1685-1690. doi: 10.1182/blood-2016-09-740308. Epub 2017 Jan 26.
PubMed 28126926Suzuki Y, Tomita A, Nakamura F, Iriyama C, Shirahata-Adachi M, Shimada K, Akashi A, Ishikawa Y, Kaneda N, Kiyoi H. Peripheral blood cell-free DNA is an alternative tumor DNA source reflecting disease status in myelodysplastic syndromes. Cancer Sci. 2016 Sep;107(9):1329-37. doi: 10.1111/cas.12994. Epub 2016 Aug 25.
PubMed 27323954Quan J, Gao YJ, Yang ZL, Chen H, Xian JR, Zhang SS, Zou Q, Zhang L. Quantitative detection of circulating nucleophosmin mutations DNA in the plasma of patients with acute myeloid leukemia. Int J Med Sci. 2015 Jan 1;12(1):17-22. doi: 10.7150/ijms.10144. eCollection 2015.
PubMed 25552914Albitar F, Ma W, Diep K, De Dios I, Agersborg S, Thangavelu M, Brodie S, Albitar M. Deep Sequencing of Cell-Free Peripheral Blood DNA as a Reliable Method for Confirming the Diagnosis of Myelodysplastic Syndrome. Genet Test Mol Biomarkers. 2016 Jul;20(7):341-5. doi: 10.1089/gtmb.2015.0278. Epub 2016 Jun 1.
PubMed 27248906Iriyama C, Tomita A, Hoshino H, Adachi-Shirahata M, Furukawa-Hibi Y, Yamada K, Kiyoi H, Naoe T. Using peripheral blood circulating DNAs to detect CpG global methylation status and genetic mutations in patients with myelodysplastic syndrome. Biochem Biophys Res Commun. 2012 Mar 23;419(4):662-9. doi: 10.1016/j.bbrc.2012.02.071. Epub 2012 Feb 20.
PubMed 22382018Vasioukhin V, Anker P, Maurice P, Lyautey J, Lederrey C, Stroun M. Point mutations of the N-ras gene in the blood plasma DNA of patients with myelodysplastic syndrome or acute myelogenous leukaemia. Br J Haematol. 1994 Apr;86(4):774-9. doi: 10.1111/j.1365-2141.1994.tb04828.x.
PubMed 7918071Buedts L, Vandenberghe P. Circulating cell-free DNA in hematological malignancies. Haematologica. 2016 Sep;101(9):997-9. doi: 10.3324/haematol.2015.131128. No abstract available.
PubMed 27582567