NCT03263936

Brief Summary

This is a pilot study using decitabine and vorinostat before and during chemotherapy with fludarabine, cytarabine and G-CSF (FLAG).

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
37

participants targeted

Target at P50-P75 for phase_1

Timeline
Completed

Started Jul 2017

Longer than P75 for phase_1

Geographic Reach
3 countries

33 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 11, 2017

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

August 21, 2017

Completed
7 days until next milestone

First Posted

Study publicly available on registry

August 28, 2017

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 9, 2020

Completed
1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 10, 2022

Completed
3.7 years until next milestone

Results Posted

Study results publicly available

October 16, 2025

Completed
Last Updated

October 16, 2025

Status Verified

May 1, 2023

Enrollment Period

3 years

First QC Date

August 21, 2017

Results QC Date

May 26, 2023

Last Update Submit

September 30, 2025

Conditions

Keywords

RelapseMyelogenousLeukemiaRefractoryAcutePediatric

Outcome Measures

Primary Outcomes (1)

  • 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

    during course 1 DLT evaluation period, approx 9 weeks

Study Arms (1)

Other

OTHER

decitabine, vorinostat, fludarabine, high dose cytarabine, filgrastim (G-CSF)

Drug: DecitabineDrug: VorinostatDrug: Filgrastim (G-CSF)Drug: FludarabineDrug: Cytarabine

Interventions

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

Also known as: Dacogen
Other

Age \<18: 180 mg/m2/day once daily PO. Age≥18: 200 mg twice daily PO.

Also known as: Zolinza, SAHA, suberoylanilide acid
Other

Given on days 5 until evidence of ANC recovery (\>500/µL)5µg/kg/dose IV or SQ (starting at hour 0)

Also known as: G-CSF, neupogen
Other

30 mg/m2/day IV over 30 minutes (starting at Hour 0 - Immediately after G-CSF)

Also known as: Fludara
Other

2000 mg/m2/day (Starting at Hour 0.5),IV over 3 hours, days 6-10

Also known as: Cytosine arabinoside, Ara-C, Cytosar
Other

Eligibility Criteria

Age1 Year - 25 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • \- Patients must be ≥ 1 and ≤25 years of age.
  • Diagnosis: Patients with relapse or refractory AML must have measurable disease ( \>M1 marrow)
  • st 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.
  • 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.
  • +18 more criteria

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (33)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Orange County

Orange, California, 92868, United States

Location

UCSF School of Medicine

San Francisco, California, 94158, United States

Location

The Children's Hospital, University of Colorado

Aurora, Colorado, 80045, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

All Children's Hospital

St. Petersburg, Florida, 33701, United States

Location

Children's Healthcare of Atlanta, Emory University

Atlanta, Georgia, 30322, United States

Location

Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

Sidney Kimmel Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

National Cancer Institute, Pediatric Oncology Branch

Bethesda, Maryland, 20892, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

C.S. Mott Children's Hospital

Ann Arbor, Michigan, 48109-0914, United States

Location

CS Mott Children's Hospital, Ann Arbor

Ann Arbor, Michigan, 48109, United States

Location

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

New York University Medical Center

New York, New York, 10016, United States

Location

Children's Hospital New York-Presbyterian

New York, New York, 10032, United States

Location

Levine Children's Hospital

Charlotte, North Carolina, 28203, United States

Location

Cincinnati Children's Hospital

Cincinnati, Ohio, 45229, United States

Location

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

Location

Texas Children's Cancer Center, Baylor

Houston, Texas, 77030, United States

Location

Primary Children's Hospital

Salt Lake City, Utah, 84113, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Sydney Children's Hospital

Randwick, New South Wales, 2031, Australia

Location

Children's Hospital at Westmead

Westmead, Australia

Location

British Columbia Children's Hospital

Vancouver, British Columbia, V6H 3V4, Canada

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Sainte Justine University Hospital

Montreal, Quebec, Canada

Location

MeSH Terms

Conditions

Leukemia, Myeloid, AcuteRecurrenceLeukemia

Interventions

DecitabineVorinostatFilgrastimGranulocyte Colony-Stimulating Factorfludarabinefludarabine phosphateCytarabine

Condition Hierarchy (Ancestors)

Leukemia, MyeloidNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AzacitidineAza CompoundsOrganic ChemicalsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosidesAnilidesAmidesAniline CompoundsAminesHydroxamic AcidsHydroxylaminesHydroxy AcidsCarboxylic AcidsColony-Stimulating FactorsGlycoproteinsGlycoconjugatesCarbohydratesHematopoietic Cell Growth FactorsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological FactorsArabinonucleosides

Results Point of Contact

Title
Ellynore Florendo
Organization
Therapeutic Advanced in Childhood Leukemia and Lymphoma

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 21, 2017

First Posted

August 28, 2017

Study Start

July 11, 2017

Primary Completion

July 9, 2020

Study Completion

February 10, 2022

Last Updated

October 16, 2025

Results First Posted

October 16, 2025

Record last verified: 2023-05

Locations