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

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.

Conditions

• Lymphoblastic Leukemia, Acute, Childhood
• Myelogenous Leukemia, Acute, Childhood

Interventions

DRUG

Azacytidine

Dose assigned at study entry (75 mg/m2/day). Given subcutaneously, once daily on days 1 to 5, for a total of 5 doses.

DRUG

Fludarabine

30 mg/m2/dose, intravenous infusion over 30 minutes, once daily, on days 6 to 10, total 5 doses

DRUG

Cytarabine

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.

DRUG

Intrathecal (IT) Cytarabine

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

DRUG

Intrathecal Methotrexate (IT MTX)

* 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

Sponsors & Collaborators

• Gateway for Cancer Research

  collaborator OTHER

• Therapeutic Advances in Childhood Leukemia Consortium

  lead OTHER

Principal Investigators

• Weili Sun, MD, PhD · Children's Hospital Los Angeles

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2013-05-22

Primary Completion

2014-07-28

Completion

2014-07-28

FDA Drug

Yes

Countries

• United States
• Australia
• Canada

Study Locations