Spots Global Cancer Trial Database for A Phase I Study of 5-Azacytidine in Combination With Chemotherapy for Children With Relapsed or Refractory ALL or AML

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Trial Identification

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

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

Study ID: NCT01861002

Conditions

Lymphoblastic Leukemia, Acute, Childhood

Myelogenous Leukemia, Acute, Childhood

Interventions

Azacytidine

Fludarabine

Cytarabine

Intrathecal (IT) Cytarabine

Intrathecal Methotrexate (IT MTX)

Study Description

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.

Detailed Description: Growing evidence indicates that aberrant DNA hypermethylation is associated with leukemia development, drug resistance, and relapse. It has been shown that pretreating leukemia cells with AZA or decitabine could partially reverse the aberrant DNA methylation, restore the expression of tumor suppressor gene important for apoptosis, and sensitize cells to subsequent killing by cytotoxic agent. Since cytarabine and decitabine share the same mechanisms of resistance, we use AZA to test the novel epigenetic "priming" approach. This is a phase I clinical study with expansion phase, using hypomethylating agent, 5-azacytidine (AZA), in sequential with chemotherapy to evaluate whether epigenetic "priming" can reverse aberrant DNA methylation, overcome drug resistance, and increase response in relapsed/refractory AML. The chemotherapy regimen to be used in this study is fludarabine and cytarabine. This regimen has substantial activity in leukemia and has been widely used in treating pediatric patients with relapsed/refractory AML and ALL in the past several decades. In BFM relapsed AML 2001/01 study, FLAG (fludarabine, cytarabine and G-CSF) chemotherapy regimen showed significant activity in AML with 4 year OS around 36%. Since the use of G-CSF in conjunction with fludarabine/cytarabine didn't improve the overall survival of patient in a randomized trial, only fludarabine and cytarabine will be used in this study to decrease the incidence of leukocytosis related complications. This regimen is very similar to the chemotherapy regimen proposed for the next relapsed AML trial within the Children's Oncology Group (COG). If this trial proves to be safe and active, it will provide the foundation and smooth transition to larger statistically powered nationwide phase II clinical trials by COG.