Acute Myelogenous LeukemiaPhase 1NCT03263936
Epigenetic Reprogramming in Relapse/Refractory AML
A Phase 1 study testing Decitabine, Vorinostat and Filgrastim (G-CSF) in people with Acute Myelogenous Leukemia, run by Therapeutic Advances in Childhood Leukemia Consortium at 33 sites in 3 countries.
Trial summary
This is a pilot study using decitabine and vorinostat before and during chemotherapy with fludarabine, cytarabine and G-CSF (FLAG). Read more about this study
- Who is it for?
- Ages 1 year to 25 years
- Conditions the study is for
- Acute Myelogenous Leukemia
- What is being tested?
- Decitabine, Vorinostat and Filgrastim (G-CSF)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 33 sitesin 3 countries
- Study dates
- 11 Jul 2017to 10 Feb 2022
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 1 year to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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).
Show all 33Show fewer
- 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.
- 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.
- 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:
- 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.
- 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.
- Female patients with infants must agree not to breastfeed their infants while on this study.
- 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.
Who cannot join
- 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)
Show all 9Show fewer
- 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
Trial locations and contacts
33 sites in 3 countries.
33 sites in 3 countries
United States28 sites
C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109-0914
CS Mott Children's Hospital, Ann Arbor
Ann Arbor, Michigan, 48109
Children's Healthcare of Atlanta, Emory University
Atlanta, Georgia, 30322
The Children's Hospital, University of Colorado
Aurora, Colorado, 80045
Johns Hopkins University
Baltimore, Maryland, 21231
Sidney Kimmel Cancer Center at Johns Hopkins
Baltimore, Maryland, 21231
National Cancer Institute, Pediatric Oncology Branch
Bethesda, Maryland, 20892
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Levine Children's Hospital
Charlotte, North Carolina, 28203
Lurie Children's Hospital of Chicago
Chicago, Illinois, 60611
Cincinnati Children's Hospital
Cincinnati, Ohio, 45229
Nationwide Children's Hospital
Columbus, Ohio, 43205
Cook Children's Medical Center
Fort Worth, Texas, 76104
Texas Children's Cancer Center, Baylor
Houston, Texas, 77030
Children's Hospital Los Angeles
Los Angeles, California, 90027
University of Miami
Miami, Florida, 33136
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
Children's Hospitals and Clinics of Minnesota
Minneapolis, Minnesota, 55404
New York University Medical Center
New York, New York, 10016
Children's Hospital New York-Presbyterian
New York, New York, 10032
Children's Hospital Orange County
Orange, California, 92868
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Oregon Health and Science University
Portland, Oregon, 97239
Primary Children's Hospital
Salt Lake City, Utah, 84113
UCSF School of Medicine
San Francisco, California, 94158
Seattle Children's Hospital
Seattle, Washington, 98105
All Children's Hospital
St. Petersburg, Florida, 33701
Children's National Medical Center
Washington D.C., District of Columbia, 20010
Canada3 sites
Sainte Justine University Hospital
Montreal, Quebec
Hospital for Sick Children
Toronto, Ontario, M5G 1X8
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4
Australia2 sites
Sydney Children's Hospital
Randwick, New South Wales, 2031
Children's Hospital at Westmead
Westmead
About this study
Official title: Epigenetic Reprogramming in Relapse AML: A Phase 1 Study of Decitabine and Vorinostat Followed by Fludarabine, Cytarabine and G-CSF (FLAG) in Children and Young Adults With Relapsed/Refractory AML
This is a pilot study using decitabine and vorinostat before and during chemotherapy with fludarabine, cytarabine and G-CSF (FLAG).
Read the detailed description
Decitabine is a demethylating agent and vorinostat is a HDAC inhibitor. The use of demethylating agents and HDAC inhibitors in combination have been previously shown to have synergistic effects in altering neoplastic pathways of cancer cells and be well tolerated in human clinical studies. With the ability of decitabine and vorinostat to alter the abnormal cellular pathways of leukemic blasts and essentially turn off anti-apoptotic proteins, the leukemia cells have become primed for cytotoxic cell kill via chemotherapeutic agents. This study will ask the question as to whether or not the combination of decitabine and vorinostat followed by chemotherapy is feasible and whether it can positively impact outcome in patients with relapsed or refractory acute myelogenous leukemia.
- Conditions
- Acute Myelogenous Leukemia
- Being tested
- Decitabine, Vorinostat, Filgrastim (G-CSF), Fludarabine, Cytarabine
- Keywords
- Relapse, Myelogenous, Leukemia, Refractory, Acute, Pediatric
- Medical subject headings
- Leukemia, Myeloid, Acute, Recurrence, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DecitabineDrug
Also called Dacogen
Dose Level #0: 5 mg/m2 Dose Level #1: 7.5 mg/m2 Dose Level #2: 10 mg/m2 Dose Level #3: 15 mg/m2 Dose Level #4: 20 mg/m2 given IV over __ hour on days 1 through 5
VorinostatDrug
Also called Zolinza, SAHA, suberoylanilide acid
Age <18: 180 mg/m2/day once daily PO. Age≥18: 200 mg twice daily PO.
Filgrastim (G-CSF)Drug
Also called G-CSF, neupogen
Given on days 5 until evidence of ANC recovery (>500/µL)5µg/kg/dose IV or SQ (starting at hour 0)
FludarabineDrug
Also called Fludara
30 mg/m2/day IV over 30 minutes (starting at Hour 0 - Immediately after G-CSF)
CytarabineDrug
Also called Cytosine arabinoside, Ara-C, Cytosar
2000 mg/m2/day (Starting at Hour 0.5),IV over 3 hours, days 6-10
| Study group | Role | What they receive |
|---|---|---|
| Other | Other | decitabine, vorinostat, fludarabine, high dose cytarabine, filgrastim (G-CSF) Receives: Drug: Decitabine; Drug: Vorinostat; Drug: Filgrastim (G-CSF); Drug: Fludarabine; Drug: Cytarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Dose of Decitabine That Can be Safely Given With Vorinostat, Fludarabine, High Dose Cytarabine and G-CSF (FLAG)
The incidence of dose limiting toxicity (DLT) will be measured. The maximum tolerated dose will be the highest study dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy
Measured: during course 1 DLT evaluation period, approx 9 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2017
- Study start11 Jul 2017
- Primary completion9 Jul 2020
- Study completion10 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Myelogenous LeukemiaStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 37 participants (actual)
Sponsor and investigators
- Lead sponsor
- Therapeutic Advances in Childhood Leukemia Consortium
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03263936
- Sponsor's protocol ID
- T2016-003
- Status last verified
- May 2023
- First submitted
- 21 Aug 2017
- Last updated
- 16 Oct 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Epigenetic Reprogramming in Relapse AML: A Phase 1 Study of Decitabine and Vorinostat Followed by Fludarabine, Cytarabine and G-CSF (FLAG) in Children and Young Adults With Relapsed/Refractory AML
- ClinicalTrials.gov ID
- NCT03263936
- Acronym / sponsor ID
- T2016-003
- Conditions
- Acute Myelogenous Leukemia
- Keywords
- Relapse, Myelogenous, Leukemia, Refractory, Acute, Pediatric
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 37 participants (actual)
- Lead sponsor
- Therapeutic Advances in Childhood Leukemia ConsortiumUniversity, hospital or other
- Study start
- 11 Jul 2017 (actual)
- Primary completion
- 9 Jul 2020 (actual)
- Study completion
- 10 Feb 2022 (actual)
- First posted
- 28 Aug 2017 (actual)
- Results
- Posted 16 Oct 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a pilot study using decitabine and vorinostat before and during chemotherapy with fludarabine, cytarabine and G-CSF (FLAG).
Detailed description
Decitabine is a demethylating agent and vorinostat is a HDAC inhibitor. The use of demethylating agents and HDAC inhibitors in combination have been previously shown to have synergistic effects in altering neoplastic pathways of cancer cells and be well tolerated in human clinical studies. With the ability of decitabine and vorinostat to alter the abnormal cellular pathways of leukemic blasts and essentially turn off anti-apoptotic proteins, the leukemia cells have become primed for cytotoxic cell kill via chemotherapeutic agents. This study will ask the question as to whether or not the combination of decitabine and vorinostat followed by chemotherapy is feasible and whether it can positively impact outcome in patients with relapsed or refractory acute myelogenous leukemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Other | Other | Drug: Decitabine, Drug: Vorinostat, Drug: Filgrastim (G-CSF), Drug: Fludarabine, Drug: Cytarabinedecitabine, vorinostat, fludarabine, high dose cytarabine, filgrastim (G-CSF) |
Who may qualify
- Ages
- 1 year to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (33 listed)
- 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
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DecitabineAlso: DacogenDose Level #0: 5 mg/m2 Dose Level #1: 7.5 mg/m2 Dose Level #2: 10 mg/m2 Dose Level #3: 15 mg/m2 Dose Level #4: 20 mg/m2 given IV over __ hour on days 1 through 5 | Drug | Other |
| VorinostatAlso: Zolinza, SAHA, suberoylanilide acidAge <18: 180 mg/m2/day once daily PO. Age≥18: 200 mg twice daily PO. | Drug | Other |
| Filgrastim (G-CSF)Also: G-CSF, neupogenGiven on days 5 until evidence of ANC recovery (>500/µL)5µg/kg/dose IV or SQ (starting at hour 0) | Drug | Other |
| FludarabineAlso: Fludara30 mg/m2/day IV over 30 minutes (starting at Hour 0 - Immediately after G-CSF) | Drug | Other |
| CytarabineAlso: Cytosine arabinoside, Ara-C, Cytosar2000 mg/m2/day (Starting at Hour 0.5),IV over 3 hours, days 6-10 | Drug | Other |
Primary outcome
The Dose of Decitabine That Can be Safely Given With Vorinostat, Fludarabine, High Dose Cytarabine and G-CSF (FLAG)
Time frame: during course 1 DLT evaluation period, approx 9 weeks
The incidence of dose limiting toxicity (DLT) will be measured. The maximum tolerated dose will be the highest study dose at which 1 or fewer of six patients experience DLT during cycle 1 of therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Undecided
Related trials for Acute Myelogenous Leukemia
Not yet recruitingPhase 1/2
A Study of Sonrotoclax (BGB-11417) in Children With Relapsed or Refractory Acute Myeloid Leukemia and B-cell Acute Lymphoblastic Leukemia
Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
RecruitingPhase 1
Autologous T Cells Transduced With Retroviral Vectors Expressing TCRs for Participant-specific Neoantigens in Patients With Hematologic Malignancies
Malignancy, Hematologic, Neoplasms, Hematologic
RecruitingPhase 2
MYELOMATCH: A Screening Study to Assign People With Myeloid Cancer to a Treatment Study or Standard of Care Treatment Within myeloMATCH (MyeloMATCH Screening Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
RecruitingPhase 2
Comparing Cytarabine + Daunorubicin Therapy Versus Cytarabine + Daunorubicin + Venetoclax Versus Venetoclax + Azacitidine in Younger Patients With Intermediate Risk AML (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia
RecruitingPhase 2
Cord Blood Transplant, Cyclophosphamide, Fludarabine, and Total-Body Irradiation in Treating Patients With High-Risk Hematologic Diseases
Acute Leukemia of Ambiguous Lineage, Acute Lymphoblastic Leukemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
33 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Decitabine, Vorinostat and Filgrastim (G-CSF) in people with Acute Myelogenous Leukemia, run by Therapeutic Advances in Childhood Leukemia Consortium at 33 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 33 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 33 sites in United States, Canada, Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Oct 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Dose of Decitabine That Can be Safely Given With Vorinostat, Fludarabine, High Dose Cytarabine and G-CSF (FLAG) (time frame: during course 1 DLT evaluation period, approx 9 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2025.