A Phase II Simon Two-stage Multicenter Study and Pilot Pharmacodynamic Investigation of GTI 2040 in Combination With High Dose Cytarabine (HiDAC) in Refractory and Relapsed Acute Myeloid Leukemia (AML)
- Patients must have unequivocal histologic diagnosis of AML according to WHO
- Patients must have (1) refractory AML, defined as a disease unresponsive to the
initial treatment; or (2) relapsed AML, defined as disease that re-occurs after
treatment with conventional or high dose chemotherapy, with or without autologous
stem cell support.
- Patients previously treated with antisense oligonucleotides remain eligible in
absence of significant or dose-limiting documented toxicities directly attributable
to the antisense agents.
- Age 18-59 years old.
- Because no dosing or adverse event data are currently available on the use of
GTI-2040 in combination with cytarabine in patients <18 years of age, children are
excluded from this study but will be eligible for future pediatric Phase 2
- ECOG performance status <= 2 (Karnofsky >60%).
- Patients with CNS involvement will be considered eligible for this study if no
residual leukemic cells are detectable in the cerebral spinal fluid following
intrathecal or radiation therapy.
- Central line catheter for administration of GTI-2040 infusion is required for all
patients enrolled in the study.
- Ability to understand and the willingness to sign a written informed consent
document. Written informed consent is required prior to any study procedures for
screening or enrolment.
- Patients who have had chemotherapy (with the exception of hydroxyurea) or
radiotherapy within 4 weeks prior to entering the study or those who have not
recovered from adverse events due to agents administered more than 4 weeks earlier.
Patients who have received mitomycin C or nitrosurea require a 6 week recovery period
- Patients who have had prior allogeneic stem cell transplant.
- Patients may not be receiving any other investigational agents as part of ongoing
- Patients with the following abnormal clinical values (unless abnormalities in these
parameters are directly attributable to malignancy):
- Resting cardiac ejection fraction < 50%
- Serum creatinine > 1.5 mg/dL
- Total bilirubin > 2x ULN (unless due to Gilbert's syndrome)
- AST and ALT > 3x ULN
- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to GTI-2040 or other agents used in the study.
- Patients who require chronic systemic anticoagulant therapy for medical conditions
(e.g., previous history of deep venous thrombosis, atrial fibrillation etc.).
Heparin administration to maintain central line patency (i.e. catheter flush) is not
- Patients with uncontrolled intercurrent illness including, but not limited to,
ongoing or active infection requiring IV antibiotics, symptomatic congestive heart
failure, unstable angina pectoris, or cardiac arrhythmia.
- Serious medical or psychiatric illness that would prevent informed consent or limit
survival to < 4 weeks.
- Pregnancy or breastfeeding women. The potential for teratogenic effects and other
risks for GTI-2040 in nursing infants are unknown. Women of childbearing potential
and men must agree to use adequate contraception (hormonal or barrier method of birth
control) prior to study entry and for the duration of study participation.
- HIV-positive patients on combination antiretroviral therapy are ineligible because
these patients are at increased risk of lethal infections when treated with
marrow-suppressive therapy. Appropriate studies will be undertaken in patients
receiving combination antiretroviral therapy when indicated.