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An Open-Label Phase I/II Study of XIAP Antisense AEG35156 Administered to Patients With Refractory/Relapsed AML in Combination With Chemotherapy

Phase 1/Phase 2
18 Years
Not Enrolling
Leukemia, Myelomonocytic, Acute

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Trial Information

An Open-Label Phase I/II Study of XIAP Antisense AEG35156 Administered to Patients With Refractory/Relapsed AML in Combination With Chemotherapy

This is a phase I/II, single-arm, open-label, study to establish the recommended dose and
activity of AEG35156 administered as a daily x3 two-hour infusion prior to reinduction
chemotherapy with idarubicin and ara-C followed by weekly two-hour AEG35156 infusions.
Subjects eligible for study entry must have confirmed diagnosis of AML in first relapse
after an initial CR that lasted less than 6 months or primary refractory AML. Fixed dose of
idarubicin and ara-C will be given, plus one of eight doses of AEG35156: 12, 24, 48, 75,
110, 165, 250 and 350mg/m2. A maximum of 54 patients will be treated in cohorts of size 3,
starting at 12mg/m2, and not skipping any untried dose level when escalating. Following
dose escalation, approximately 20 patients will be treated at the best acceptable dose as
determined by the method of Thall and Cook (2004).

Inclusion Criteria

Inclusion Criteria

- Subjects with relapsed or refractory AML, except those with APL (acute promyelocytic
leukemia), that are about to receive their initial treatment for first relapse after
an initial CR that lasted less than 6 months or for primary refractory AML that have
an expected complete response rate ≤20%. The initial diagnosis of AML has to be
based on the presence of > 10% blasts in marrow or blood, and the diagnosis of
relapsed/refractory AML based on the presence of either > 10% blasts in marrow or
blood or 5-10% blasts in either site together with cytopenia (Hb < 10 g/dL, or
platelets < 100,000 /uL, or neutrophil count < 1000 /uL).

- Peripheral AML blast count < 50,000 /uL that is not projected to rise above 50,000
/uL within 5 days of beginning treatment.

- Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of

- Subjects must be >18 years old.

- Male, or female subjects who are post-menopausal (amenorrhagic for at least 12
months), or surgically or biologically sterile. Females of childbearing potential
with a negative serum pregnancy test 72-96 hours prior to the 1st infusion in the
study and using adequate forms of contraception for the duration of the study,
including 30 days after the last treatment. Adequate methods of contraception should
be used by both male and female subjects.

- Subjects must have adequate organ and immune function as indicated by the following
laboratory values:

- Parameter Laboratory Values

- Serum creatinine; <2.0mg/dL

- Total Bilirubin <2.0mg/dL

- AST (SGOT) and ALT (SGPT) <3 X ULN * *ULN: Institution's upper limit of normal.

- The subject must understand and be able and willing and likely to fully comply with
study procedures, including scheduled follow-up, and restrictions.

- The subject, or the subject's legal guardian, must have given written personally
signed and dated informed consent to participate in the study, in accordance with the
International Conference on Harmonization (ICH) Good Clinical Practice (GCP)
Guidelines, before completing any study related procedures.

Exclusion Criteria

- Clinical evidence of active CNS leukemic involvement.

- Patients with left-ventricular ejection fractions <50%.

- Active and uncontrolled infection. Patients with an infection that are under active
treatment with antibiotics and whose infections are controlled may be entered to the

- Current evidence of invasive fungal infection (blood or tissue culture).

- Current evidence of an active second malignancy except for non-melanoma skin cancer.

- Uncontrolled medical problems, unrelated to the malignancy, or of sufficient severity
that in the opinion of the investigator, impair a subject's ability to give informed
consent or unacceptably reduce the safety of the proposed treatment.

- Neurological or psychiatric disorders that would interfere with consent or study

- Known or suspected intolerance or hypersensitivity to the study materials [or closely
related compounds] or any of their stated ingredients.

- History of alcohol or other substance abuse within the last year.

- Use of another investigational agent or participation in a clinical trial within the
last 14 days prior to enrolment. Subjects who have used a previous AS agent for at
least 90 days will be excluded.

- Female subjects who are pregnant or lactating, or females with a positive pregnancy
test at screening must be excluded.

- Subjects that have previously been enrolled into this study and subsequently
withdrawn must also be excluded.

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:

Dose at which AEG35156 when combined with fixed doses of ara-C and idarubicin, produces acceptable CR and toxicity rates as defined and observed at 30 days post-last dose

Outcome Time Frame:

1 year

Safety Issue:


Principal Investigator

Jacques Jolivet, MD

Investigator Role:

Study Director

Investigator Affiliation:

Aegera Therapeutics Inc.


United States: Food and Drug Administration

Study ID:




Start Date:

October 2005

Completion Date:

March 2009

Related Keywords:

  • Leukemia, Myelomonocytic, Acute
  • AML
  • leukemia
  • relapse
  • refractory
  • antisense
  • oligonucleotide
  • Leukemia
  • Leukemia, Myelomonocytic, Acute



Northwestern Memorial Hospital Chicago, Illinois  60611
UCLA Medical Center Los Angeles, California  90095-7059
M.D. Anderson Cancer Center Houston, Texas  77030
Norris Cancer Center - University of Southern California Los Angeles, California  90033
Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center Baltimore, Maryland  21231