New hope for young AML patients: epigenetic drugs plus chemotherapy show promise

NCT ID NCT03263936

Disease control Sponsor: Therapeutic Advances in Childhood Leukemia Consortium Source: ClinicalTrials.gov ↗

First seen Jun 27, 2026 · Last updated Jun 27, 2026

Summary

This early-phase study tested whether adding two drugs (decitabine and vorinostat) before and during standard chemotherapy (FLAG) is safe for children and young adults up to age 25 with acute myeloid leukemia (AML) that has come back or not responded to treatment. The goal was to find the highest safe dose of decitabine when used in this combination. The study enrolled 37 participants and measured side effects to determine the best dose for future studies.

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Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 1

The first testing in people. Mainly checks safety and dose, usually in a small group.

Participants

37 people

The number who actually took part.

Started

Jul 2017

Finished

Feb 2022

Lead sponsor

Other sponsor

The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

1 year to 25 years

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: \- Patients must be ≥ 1 and ≤25 years of age. Diagnosis: Patients with relapse or refractory AML must have measurable disease ( \>M1 marrow) * 1st or greater relapse, OR * Failed to go into remission after 1st or greater relapse, OR * Failed to go into remission from original diagnosis after 2 or more induction attempts Eligibility for patients with an M1 marrow; defined as \>0.1% by flow or molecular testing (e.g. PCR). * must include two serial marrows (at least 1-week apart) demonstrating stable or rising minimal residual disease (MRD) (i.e. not declining). * Patients may have CNS or other sites of extramedullary disease. No cranial irradiation is allowed during the protocol therapy. * Patients with secondary AML are eligible. * Patients with Down syndrome are eligible. * Patients with DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded. Performance Level: \- Karnofsky \>50% for patients \>16 years of age and Lansky \> 50% for patients ≤ 16 years of age (See Appendix II for Performance Scales) Prior therapy - Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. 1. Cytoreduction with hydroxyurea: hydroxyurea can be initiated and continued for up to 24 hours prior to the start of decitabine/vorinostat. It is recommended to use hydroxyurea in patients with significant leukocytosis (WBC \>50,000/L) to control blast count before initiation of systemic protocol therapy. 2. Patients who relapsed while they are receiving cytotoxic therapy: at least 14 days must have elapsed since the completion of the cytotoxic therapy, except Intrathecal chemotherapy. Hematopoietic stem cell transplant (HSCT): \- Patients who have experienced their relapse after a HSCT are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD) and are off all transplant immune suppression therapy for at least 7-days (e.g. steroids, cyclosporine, tacrolimus). Steroid therapy for non-GVHD and/or non-leukemia therapy is acceptable. Hematopoietic growth factors: \- It must have been at least 7 days since the completion of therapy with GCSF or other growth factors at the time of enrollment. It must have been at least 14 days since the completion of therapy with pegfilgrastim (Neulasta ®) Biologic (anti-neoplastic agent): -At least 7 days after the last dose of a biologic agent. For agents that have known adverse events occurring beyond 7 days after administration, this period must be extended beyond the time during which adverse events are known to occur. The duration of this interval must be discussed with the study chair. Monoclonal antibodies: At least 3 half-lives of the antibody must have elapsed after the last dose of monoclonal antibody (i.e. Gemtuzumab = 36 days) Immunotherapy: At least 42 days after the completion of any time of immunotherapy, e.g. tumor vaccines or CAR T-cell therapy. XRT: Cranio or craniospinal XRT is prohibited during protocol therapy. No washout period is necessary for radiation given to non-CNS chloromas; \>90 days must have elapsed if prior TBI, cranio or craniospinal XRT. Prior Demethylating and/or HDAC Inhibitor Therapy: Patients who have received prior DNMTi (e.g. decitabine) and/or HDACi (e.g. vorinostat) therapy are eligible to participate in this Phase 1 study. At least 7 days must have passed from prior DNMTi or HDACi as a washout period. Renal and hepatic function: Patients must have adequate renal and hepatic functions as indicated by the following laboratory values: A. Adequate renal function defined as: Patient must have a calculated creatinine clearance or radioisotope GFR ≥ 70ml/min/1.73m2 OR a normal serum creatinine based on age/gender. B. Adequate Liver Function Defined as: Direct bilirubin \< 1.5 x upper limit of normal (ULN) for age or normal, AND alanine transaminase (ALT) \< 5 x ULN for age. The hepatic requirements are waived for patients with known or suspected liver involvement by leukemia. This must be reviewed by and approved by the study chair or vice chair. Adequate Cardiac Function Defined as: Shortening fraction of ≥ 27% by echocardiogram, OR ejection fraction of ≥ 50% by radionuclide angiogram (MUGA). Reproductive Function A. Female patients of childbearing potential must have a negative urine or serum pregnancy test confirmed within 1 week prior to enrollment. B. Female patients with infants must agree not to breastfeed their infants while on this study. C. Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 6 months after study treatment. Exclusion Criteria: * No NG or G-Tube administration of Vorinostat is allowed. Capsule must be swallowed whole or given as oral suspension. * They are currently receiving other investigational drugs. * There is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period. * They have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results. * They have a known allergy to any of the drugs used in the study. * Patients with DNA fragility syndromes are excluded (e.g. Fanconi Anemia, Bloom Syndrome) * They are receiving valproic acid (VPA) therapy. * Patients with Acute Promyelocytic Leukemia (APL, APML) are excluded * Patients with documented active and uncontrolled infection at the time of study entry are not eligible

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Conditions

The condition(s) this trial relates to.

acute myeloid leukemia leukemia Recurrence

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Acute myelogenous leukemia

Contacts and locations

Locations

All Children's Hospital

St. Petersburg, Florida, 33701, United States
British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada
C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109-0914, United States
CS Mott Children's Hospital, Ann Arbor

Ann Arbor, Michigan, 48109, United States
Children's Healthcare of Atlanta, Emory University

Atlanta, Georgia, 30322, United States
Children's Hospital Los Angeles

Los Angeles, California, 90027, United States
Children's Hospital New York-Presbyterian

New York, New York, 10032, United States
Children's Hospital Orange County

Orange, California, 92868, United States
Children's Hospital at Westmead

Westmead, Australia
Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States
Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States
Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States
Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States
Cook Children's Medical Center

Fort Worth, Texas, 76104, United States
Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States
Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada
Johns Hopkins University

Baltimore, Maryland, 21231, United States
Levine Children's Hospital

Charlotte, North Carolina, 28203, United States
Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States
Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States
National Cancer Institute, Pediatric Oncology Branch

Bethesda, Maryland, 20892, United States
Nationwide Children's Hospital

Columbus, Ohio, 43205, United States
New York University Medical Center

New York, New York, 10016, United States
Oregon Health and Science University

Portland, Oregon, 97239, United States
Primary Children's Hospital

Salt Lake City, Utah, 84113, United States
Sainte Justine University Hospital

Montreal, Quebec, Canada
Seattle Children's Hospital

Seattle, Washington, 98105, United States
Sidney Kimmel Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States
Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia
Texas Children's Cancer Center, Baylor

Houston, Texas, 77030, United States
The Children's Hospital, University of Colorado

Aurora, Colorado, 80045, United States
UCSF School of Medicine

San Francisco, California, 94158, United States
University of Miami

Miami, Florida, 33136, United States

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