EZN-3042 Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL)

Summary

An experimental drug called EZN-3042 targets survivin, a protein expressed in leukemia cells at relapse that promotes the leukemia cells to grow. The main goal of this phase I study is to find out the dose of EZN-3042 that can be safely given without serious side effects both alone and in combination with standard chemotherapy drugs during re-induction.

Conditions

• Lymphoblastic Leukemia, Acute
• Lymphoblastic Leukemia, Acute, Childhood
• Leukemia, Lymphoblastic, Acute, T Cell
• Leukemia, Lymphoblastic, Acute

Interventions

DRUG

EZN-3042

Dose will be assigned at study entry. To be given as a 2 hour intravenous infusion on days -5, -2, 8, 15, 22 and 29. Dose levels: L0 (level zero): 1.5 mg/kg, L1: 2.5 mg/kg, L2: 5 mg/kg, L3: 6.5 mg/kg

DRUG

Cytarabine

Given intrathecally on day -6. Patients who may have received intrathecal chemotherapy within 7 days of day 0 as part of their prior maintenance chemotherapy (e.g. before the diagnosis of relapse) or as part of the diagnostic workup will not receive this dose of IT cytarabine. If given, dose is defined by age: 1-1.99 years: 30 mg 2-2.99 years: 50 mg Greater than or equal to 3 years: 70 mg. Cytarabine is also part of the triple intrathecal therapy given to CNS 3 patients on Days 8, 15, 22 and 29. Dose is defined by age: 1. \- 1.99 years: 16 mg 2. \- 2.99 years: 20 mg 3. \- 8.99 years: 24 mg Greater than or equal to 9 years: 30 mg

DRUG

Doxorubicin

60 mg/m2/day given intravenous infusion (IV) over 15 minutes on day 1.

DRUG

Prednisone

40 mg/m2/day divided BID or TID given orally on days 1 through 29. For patients who are unable to tolerate prednisone orally, substitute IV methylprednisolone at 80% of the oral prednisone dose.

DRUG

Vincristine

1.5 mg/m2/day (maximum dose 2 mg) given intravenous push over 1 minute or infusion via mini-bag as per institutional policy on days 1, 8, 15 and 22.

DRUG

PEG-asparaginase

2500 IU/m2 intramuscular injection on days 2, 9, 16, 23. If available, Erwinia L-asparaginase may be substituted for pegaspargase in patients with clinically significant prior allergies to pegaspargase.

DRUG

Methotrexate

Given intrathecally to patients with CNS1 or CNS2 disease at the dose defined by age below on days 15 and 36: 1-1.99 years: 8 mg 2-2.99 years: 10 mg 3-8.99 years: 12 mg Greater than or equal to 9 years: 15 mg Given as part of the Triple intrathecal therapy to patients with CNS 3 disease at the doses defined by age below on days 8, 15, 22 and 29: 1. \- 1.99 years: 8 mg 2. \- 2.99 years: 10 mg 3. \- 8.99 years: 12 mg Greater than or equal to 9 years: 15 mg

DRUG

Hydrocortisone

Given as part of the Triple intrathecal therapy to patients with CNS 3 disease at the doses defined by age below on days 8, 15, 22 and 29: 1. \- 1.99 years: 8 mg 2. \- 2.99 years: 10 mg 3. \- 8.99 years: 12 mg Greater than or equal to 9 years: 15 mg

Sponsors & Collaborators

• Enzon Pharmaceuticals, Inc.

  collaborator INDUSTRY

• Therapeutic Advances in Childhood Leukemia Consortium

  lead OTHER

Principal Investigators

• Elizabeth Raetz, MD · NYU Langone Health

• William Carroll, MD · NYU Langone Health

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

1 Year

Max Age

21 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2010-08-24

Primary Completion

2012-01-10

Completion

2012-01-10

FDA Drug

Yes

Countries

• United States
• Australia

Study Locations