A Phase I Study of 5-Azacytidine in Combination With Chemotherapy for Children With Relapsed or Refractory ALL or AML
1 other identifier
interventional
15
3 countries
23
Brief Summary
This is a Phase I study with a conditional cohort expansion phase to evaluate the feasibility of, and to obtain preliminary efficacy data about, pretreatment with Azacytidine (AZA) for 5 days followed by fludarabine/cytarabine chemotherapy regimen in pediatric acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) patients who are refractory to primary treatment or who relapsed.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started May 2013
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 21, 2013
CompletedStudy Start
First participant enrolled
May 22, 2013
CompletedFirst Posted
Study publicly available on registry
May 23, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 28, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
July 28, 2014
CompletedResults Posted
Study results publicly available
April 30, 2021
CompletedJune 9, 2021
May 1, 2021
1.2 years
May 21, 2013
October 3, 2018
May 14, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants Who Experienced a Dose Limiting Toxicity (DLT)
To evaluate the side effects of giving Azacytidine before and during chemotherapy using the standard drugs Fludarabine, Cytarabine, IT Cytarabine (AML patients) and IT methotrexate (ALL patients)
From Day 1 to Day 42 (Cycle 1)
Secondary Outcomes (1)
Disease Response Rate After Treatment
Between Days 36-42 of Courses 1 and 2
Study Arms (2)
AML Arm
EXPERIMENTALParticipants with Acute Myeloid Leukemia (AML) Intervention: * Azacytidine (Dose Level 1 @ 75 mg/m2/day) * Fludarabine 30 mg/m2/dose * Cytarabine 2000 mg/m2/dose * Intrathecal (IT) Cytarabine
ALL Arm
EXPERIMENTALPatients with Acute Lymphocytic Leukemia Intervention: * Azacytidine (Dose Level 1 @ 75 mg/m2/day) * Fludarabine 30 mg/m2/dose * Cytarabine 2000 mg/m2/dose * Intrathecal Methotrexate (IT MTX)
Interventions
Dose assigned at study entry (75 mg/m2/day). Given subcutaneously, once daily on days 1 to 5, for a total of 5 doses.
30 mg/m2/dose, intravenous infusion over 30 minutes, once daily, on days 6 to 10, total 5 doses
2000 mg/m2/dose intravenous infusion over 3 hours, starting 4 hours after the beginning of fludarabine, once daily, on days 6 to 10, total 5 doses.
Intrathecally to AML patients on day 1 of course 1 and 2. * Omit on day 1 of course 1 if patient received IT therapy within 7 days prior to study enrollment * IT therapy may be given during the end of course 1 disease evaluation and repeated every 7 days * For patients with CNS disease, IT cytarabine can be given weekly until the CSF is clear. Two additional doses of IT cytarabine should be given weekly after the initial CSF clearing. It is permitted to change to intrathecal triple therapy (ITT) if persistent blasts are present in the CSF based on the treating physician's clinical judgment. Cytarabine dose defined by age: * 30 mg for patients age 1-1.99 * 50 mg for patients age 2-2.99 * 70 mg for patients \>3 years of age ITT Dosing: Age (yrs) - Dose Methotrexate (MTX), Hydrocortisone (HC), Cytarabine (ARAC): 1. \- 1.99 MTX: 8 mg, HC: 15 mg, ARAC: 30 mg 2. \- 2.99 MTX: 10 mg, HC: 25 mg, ARAC: 50 mg * 3 - MTX: 12 mg, HC: 35 mg, ARAC: 70 mg
* Intrathecally to patients with ALL on day 1 of course 1 and 2. * Omit IT MTX on Day 1 of course 1 if patient received IT therapy within 7 days prior to study enrollment * IT therapy may be given during the end of course 1 disease evaluation and repeated every 7 days * For patients with CNS 2 or 3 disease, IT MTX can be given weekly until the CSF is clear. Two additional doses of IT MTX should be given weekly after the initial clearing of the CSF. It is permitted to change to ITT if persistent blasts are present in the CSF. Methotrexate dose defined by age * 8 mg for patients age 1-1.99 * 10 mg for patients age 2-2.99 * 12 mg for patients 3-8.99 years of age * 15 mg for patients \>9 years of age Triple IT Therapy Dosing: Age (yrs): Dose Methotrexate (MTX), Hydrocortisone (HC), Cytarabine (ARAC): 1. \- 1.99 MTX: 8 mg, HC: 8 mg, ARAC: 16 mg 2. \- 2.99 MTX: 10 mg, HC: 10 mg, ARAC: 20 mg 3. \- 8.99 MTX: 12 mg, HC: 12 mg, ARAC: 24 mg * 9 MTX: 15 mg, HC: 15 mg, ARAC: 30 mg
Eligibility Criteria
You may qualify if:
- Patients must be ≥ 1 and ≤ 21 years of age.
- Diagnosis
- Patients with AML must have ≥5% blasts (by morphology) in the bone marrow.
- Patients with ALL must have an M2 or M3 marrow (≥5% blasts by morphology).
- Patients may have disease in the central nervous system (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 and DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded.
- Karnofsky \> 50% for patients \> 16 years of age and Lansky \> 50% for patients ≤ 16 years of age.
- Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.
- Myelosuppressive chemotherapy - the eligibility criteria is different between phase I and expansion phase
- Phase I
- Any patient with AML in 1st or greater relapse, OR
- Any patient with ALL in 2nd or greater relapse, OR
- Patients with AML or ALL failed to go into remission after first or greater relapse, OR
- Patients with AML or ALL failed to go into remission from original diagnosis after two or more courses of induction attempts.
- +19 more criteria
You may not qualify if:
- Patients will be excluded if they have a known allergy to any of the drugs used in the study.
- Patients will be excluded if they have a systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient needs to be off pressors and have negative blood cultures for 48 hours.
- Patients will be excluded if there is a plan to administer non-protocol chemotherapy, radiation therapy, or immunotherapy during the study period.
- Patients will be excluded if they have significant concurrent disease, illness, psychiatric disorder or social issue that would compromise patient safety or compliance with the protocol treatment or procedures, interfere with consent, study participation, follow up, or interpretation of study results.
- Patients with Down syndrome and DNA fragility syndromes (such as Fanconi anemia, Bloom syndrome) are excluded.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (23)
Childrens Hospital Los Angeles
Los Angeles, California, 90027, United States
UCSF School of Medicine
San Francisco, California, 94143-0106, United States
Children's National Medical Center
Washington D.C., District of Columbia, 20010, United States
Children's Healthcare of Atlanta, Emory University
Atlanta, Georgia, 30322, United States
Johns Hopkins University
Baltimore, Maryland, 21287, United States
Dana Farber
Boston, Massachusetts, 02215, United States
C.S. Mott Children's Hospital
Ann Arbor, Michigan, 48109-0914, United States
Childrens Hospital & Clinics of Minnesota
Minneapolis, Minnesota, 55404-4597, United States
Children's Mercy Hospitals and Clinics
Kansas City, Missouri, 64108, United States
Children's Hospital New York-Presbyterian
New York, New York, 10032, United States
Levine Children's Hospital at Carolinas Medical Center
Charlotte, North Carolina, 28203, United States
Rainbow Babies & Children's Hospital
Cleveland, Ohio, 44106, United States
Nationwide Childrens Hospital
Columbus, Ohio, 43205, United States
Vanderbilt Children's Hospital
Nashville, Tennessee, 37232, United States
University of Texas at Southwestern
Dallas, Texas, 75235, United States
Cook Children's Medical Center
Fort Worth, Texas, 76104, United States
Primary Children's Medical Center
Salt Lake City, Utah, 84113, United States
Seattle Children's Hospital
Seattle, Washington, 98105, United States
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Sydney Children's Hospital
Randwick, New South Wales, 2031, Australia
Children's Hospital at Westmead
Westmead, New South Wales, 2145, Australia
British Columbia Children's Hospital
Vancouver, British Columbia, V6H 3V4, Canada
Sainte-Justine University Hospital Center
Montreal, Quebec, H3T-1C5, Canada
Related Publications (1)
Sun W, Triche T Jr, Malvar J, Gaynon P, Sposto R, Yang X, Bittencourt H, Place AE, Messinger Y, Fraser C, Dalla-Pozza L, Salhia B, Jones P, Wayne AS, Gore L, Cooper TM, Liang G. A phase 1 study of azacitidine combined with chemotherapy in childhood leukemia: a report from the TACL consortium. Blood. 2018 Mar 8;131(10):1145-1148. doi: 10.1182/blood-2017-09-803809. Epub 2018 Jan 16. No abstract available.
PMID: 29339403RESULT
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Roy Leong, BA, CCRP
- Organization
- Therapeutic Advances in Childhood Leukemia & Lymphoma (TACL) / Children's Hospital Los Angeles
Study Officials
- STUDY CHAIR
Weili Sun, MD, PhD
Children's Hospital Los Angeles
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 21, 2013
First Posted
May 23, 2013
Study Start
May 22, 2013
Primary Completion
July 28, 2014
Study Completion
July 28, 2014
Last Updated
June 9, 2021
Results First Posted
April 30, 2021
Record last verified: 2021-05
Data Sharing
- IPD Sharing
- Will not share