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T2009-007: A Phase I Study Evaluating the Safety, Tolerability and Biological Activity of EZN-3042, a Survivin mRNA Antagonist, Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL) [IND 108753]

Phase 1
1 Year
21 Years
Not Enrolling
Lymphoblastic Leukemia, Acute, Lymphoblastic Leukemia, Acute, Childhood, Leukemia, Lymphoblastic, Acute, T Cell, Leukemia, Lymphoblastic, Acute

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Trial Information

T2009-007: A Phase I Study Evaluating the Safety, Tolerability and Biological Activity of EZN-3042, a Survivin mRNA Antagonist, Administered With Re-induction Chemotherapy in Children With Relapsed Acute Lymphoblastic Leukemia (ALL) [IND 108753]

This is a phase I multi-site study of the new investigational agent EZN-3042, which is
highly effective at blocking survivin and inhibiting survivin protein expression. Survivin
plays pivotal roles in tumor formation by inhibiting cell death and regulating cell cycle
progression. The primary objective is to study EZN-3042 in children with relapsed acute
lymphoblastic leukemia (ALL). Patients will receive 2 doses of EZN-3042 prior to initiating
systemic therapy with vincristine, doxorubicin, prednisone and PEG-asparaginase. In
addition, blood and bone marrow specimens will be drawn to measure minimal residual disease
(MRD), pharmacokinetic levels of EZN-3042 and survivan expression. The study will follow a
standard 3+3 dose escalation design. We hypothesize that EZN-3042 will be safe, tolerable
and biologically active, when given both alone and in combination with standard re-induction

Inclusion Criteria:

- Patients must be ≥1 and ≤ 21 years of age when originally diagnosed with acute
lymphoblastic leukemia (ALL).

- Patients must have a diagnosis of second or greater relapse B-precursor acute
lymphoblastic leukemia (ALL) with ≥25% blasts in the bone marrow (M3), with or
without extramedullary disease.

- Patients may have central nervous system 1, 2 or 3 disease.

- Karnofsky ≥ 50 for patients > 10 years of age and Lansky ≥ 50 for patients ≤ 10 years
of age.

- Patients who relapse while receiving standard ALL maintenance chemotherapy will not
be required to have a waiting period before entry onto this study.

- Patients who relapse when they are not receiving standard ALL maintenance therapy
must have fully recovered from grade 3 or 4 toxic effects of all prior chemotherapy,
immunotherapy, or radiotherapy prior to entering this study.

- Cytotoxic Therapy: It must be at least 14 days since the completion of cytotoxic
therapy (excluding hydroxyurea) at the time of study enrollment.

- Hematopoietic Stem Cell Transplant (HSCT): Patients who have experienced their
relapse after a HSCT are eligible, provided they have no evidence of active
Graft-versus-Host Disease (GVHD) and are at least 120 days post-transplant at the
time of enrollment.

- Prior anthracycline exposure: Patients must have ≤ 400 mg/m2 lifetime exposure of
anthracycline chemotherapy.

- Biologic (anti-neoplastic) therapy: It must be at least 7 days since the completion
of therapy with a biologic agent at the time of study enrollment. For agents that
have known adverse events occurring 7 days after administration, this period must be
extended beyond the time during which adverse events are known to occur.

- Patients must have a calculated creatinine clearance or radioisotope GRF ≥
70mL/min/1.73m2 OR a normal serum creatinine based on the institutional normal values
according to age.

- Patient's ALT must be < 5 x institutional upper limit of norm (ULN), unless the
elevation is suspected to be disease-related.

- Patient's total bilirubin must be ≤ 1.5 x ULN.

- Patient's serum albumin must be ≥ 2 g/dL.

- Patient must have prothrombin time (PT), partial thromboplastin time (PTT) and
international normalized ratio (INR) ≤ 1.5 times the ULN.

- Patient must have a shortening fraction ≥ 27% by echocardiogram or an ejection
fraction ≥ 45% by gated nucleotide study.

- Female patients of childbearing potential must have a negative urine or serum
pregnancy test confirmed prior to enrollment.

- Female patients with infants must agree not to breastfeed their infants while on this

- Male and female patients of child-bearing potential must agree to use an effective
method of contraception approved by the investigator during the study.

Exclusion Criteria:

- Patients with Down syndrome are excluded.

- Patients with B-cell ALL (L3 morphology or evidence of myc translocation by molecular
or cytogenetic technique) are not eligible

- Patients with documented active and uncontrolled infection at the time of study entry
are not eligible.

- Patient will be excluded if they are currently receiving other investigational drugs.

- Patients will be excluded if they are taking strong CYP3A4 inducers or inhibitors.

- 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, interfere with consent, study participation, follow up, or interpretation
of study results.

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To determine the safety and tolerability of administering EZN-3042 as a single agent and in combination with chemotherapy, for children with relapsed B-precursor acute lymphoblastic leukemia (ALL)

Outcome Time Frame:

1.5 months

Safety Issue:


Principal Investigator

Elizabeth Raetz, MD

Investigator Role:

Study Chair

Investigator Affiliation:

New York University School of Medicine


United States: Food and Drug Administration

Study ID:




Start Date:

August 2010

Completion Date:

June 2012

Related Keywords:

  • Lymphoblastic Leukemia, Acute
  • Lymphoblastic Leukemia, Acute, Childhood
  • Leukemia, Lymphoblastic, Acute, T Cell
  • Leukemia, Lymphoblastic, Acute
  • Relapse
  • T cell
  • Lymphoblastic
  • Leukemia
  • EZN3042
  • Refractory
  • Precursor B
  • Pre B cell
  • Survivan
  • Acute
  • Childhood
  • Pediatric
  • Leukemia
  • Leukemia, Lymphoid
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Acute Disease
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma



Johns Hopkins University Baltimore, Maryland  21205
Stanford University Medical Center Stanford, California  94305-5408
Phoenix Children's Hospital Phoenix, Arizona  85016-7710
Childrens Hospital Los Angeles Los Angeles, California  90027
Vanderbilt Children's Hospital Nashville, Tennessee  37232-6310
City of Hope Duarte, California  91010
New York University Medical Center New York, New York  10016
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C.S. Mott Children's Hospital Ann Arbor, Michigan  48109-0914
Childrens Hospital & Clinics of Minnesota Minneapolis, Minnesota  55404-4597
Children's Hospital New York-Presbyterian New York, New York  10032
Miller Children's Hospital Long Beach, California  90806
Children's Memorial Chicago, Illinois  60614
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University of Minnesota Children's Hospital Minneapolis, Minnesota  
Nationwide Childrens Hospital Columbus, Ohio  
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