A Phase I Study of 5-Azacytidine in Combination With Chemotherapy for Children With Relapsed or Refractory ALL or AML

Completed · Phase 1

Conditions studied: Lymphoblastic Leukemia, Acute, Childhood, Myelogenous Leukemia, Acute, Childhood

In brief

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.

Key facts

Study ID

NCT01861002

Run by

Therapeutic Advances in Childhood Leukemia Consortium

People needed

15

Starts

2013-05-22

Expected to finish

2014-07-28

Last updated by the study team

2021-06-09

Who can join

Age: 1 and older, up to 21. Sex: any. Healthy volunteers: not accepted.

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.
• Expansion phase - will be restricted to AML patients only
• Cytoreduction with hydroxyurea can be initiated and continued for up to 24 hours prior to the start of azacytidine. 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 (including AZA , decitabine, or vorinostat) At least 14 days must have elapsed since the completion of the cytotoxic therapy.
• Hematopoietic stem cell transplant: Patients who have experienced their relapse after a stem cell transplant are eligible, provided they have no evidence of acute or chronic Graft-versus-Host Disease (GVHD) and are at least 90 days post-transplant at the time of enrollment.
• Hematopoietic growth factors: It must have been at least 7 days since the completion of therapy with filgrastim 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 type of immunotherapy, e.g. tumor vaccines.
• Radiation Therapy (XRT): 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 total body radiation or craniospinal radiation.
• Renal and hepatic function

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.

Where it is running

• Childrens Hospital Los Angeles — Los Angeles, California, United States
• UCSF School of Medicine — San Francisco, California, United States
• Children's National Medical Center — Washington D.C., District of Columbia, United States
• Children's Healthcare of Atlanta, Emory University — Atlanta, Georgia, United States
• Johns Hopkins University — Baltimore, Maryland, United States
• Dana Farber — Boston, Massachusetts, United States
• C.S. Mott Children's Hospital — Ann Arbor, Michigan, United States
• Childrens Hospital & Clinics of Minnesota — Minneapolis, Minnesota, United States
• Children's Mercy Hospitals and Clinics — Kansas City, Missouri, United States
• Children's Hospital New York-Presbyterian — New York, New York, United States
• Levine Children's Hospital at Carolinas Medical Center — Charlotte, North Carolina, United States
• Rainbow Babies & Children's Hospital — Cleveland, Ohio, United States
• Nationwide Childrens Hospital — Columbus, Ohio, United States
• Vanderbilt Children's Hospital — Nashville, Tennessee, United States
• University of Texas at Southwestern — Dallas, Texas, United States
• Cook Children's Medical Center — Fort Worth, Texas, United States
• Primary Children's Medical Center — Salt Lake City, Utah, United States
• Seattle Children's Hospital — Seattle, Washington, United States
• Children's Hospital of Wisconsin — Milwaukee, Wisconsin, United States
• Sydney Children's Hospital — Randwick, New South Wales, Australia
• Children's Hospital at Westmead — Westmead, New South Wales, Australia
• British Columbia Children's Hospital — Vancouver, British Columbia, Canada
• Sainte-Justine University Hospital Center — Montreal, Quebec, Canada

Full record on ClinicalTrials.gov

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