Combination of GTI-2040 and Cytarabine in the Treatment of Refractory and Relapsed Acute Myeloid Leukemia (AML)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00565058
Recruitment Status : Completed
First Posted : November 29, 2007
Results First Posted : July 27, 2015
Last Update Posted : July 27, 2015
Ohio State University
Information provided by (Responsible Party):
Aptose Biosciences Inc.

Brief Summary:
This is a Phase II trial conducted at multiple centers for evaluation of the pharmacodynamic activity and the overall response rate contributed by the combination agents of GTI-2040 and High Dose Cytarabine (HiDAC) in Refractory and Relapsed Acute Myeloid Leukemia (AML).

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Biological: GTI-2040 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Study Start Date : August 2007
Actual Primary Completion Date : September 2009
Actual Study Completion Date : February 2010

Arm Intervention/treatment
Experimental: Pilot
Pilot PD Study (Delayed GTI-2040) Group: In the Pilot PD Study Group, addition of GTI-2040 is delayed until 24 hours after initiation of HiDAC.
Biological: GTI-2040
GTI-2040 will be administered one day after HiDAC in the pilot PD study and one day before HiDAC in the Phase II study for a cycle. Those who achieve a complete remission (CR) will be permitted to receive one cycle of consolidation of GTI-2040 and HiDAC

Experimental: Phase II arm
Phase II PD Study (Early GTI-2040) Group: In the Phase II PD Study Group, GTI-2040 is given 24 hours prior to addition of HiDAC.
Biological: GTI-2040
GTI-2040 will be administered one day after HiDAC in the pilot PD study and one day before HiDAC in the Phase II study for a cycle. Those who achieve a complete remission (CR) will be permitted to receive one cycle of consolidation of GTI-2040 and HiDAC

Primary Outcome Measures :
  1. Overall Response Rate of GTI-2040 Combined With HiDAC in Refractory or Relapsed AML [ Time Frame: at 29-35 days ]
    Overall Response was defined as whether or not the patient achieved complete remission (CR) and CR with incomplete blood count recovery (CRi) while on the study.

Secondary Outcome Measures :
  1. Summary of Treatment Emergent Adverse Events [ Time Frame: 30 days after the last dose ]
    An adverse event (AE) was defined as any unintended or undesirable experience that occurred during the course of the clinical investigation, regardless of whether or not it was considered to be study drug-related. This included any newly occurring event or a previous condition that had increased in severity or frequency since the administration of study drug.

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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients must have unequivocal histologic diagnosis of AML according to WHO classification.
  • 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 combination trials.
  • Eastern Cooperative Oncology Group (ECOG) performance status <= 2 (Karnofsky >60%).
  • Patients with central nervous system (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 enrollment.

Exclusion Criteria:

  • 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 before enrollment.
  • Patients who have had prior allogeneic stem cell transplant.
  • Patients may not be receiving any other investigational agents as part of ongoing treatment.
  • 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 upper limits of normal (ULN) (unless due to Gilbert's syndrome)
    • aspartate aminotransferase (AST) and alanine aminotransferase (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 an exclusion.
  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00565058

United States, California
San Francisco Veterans Affairs Medical Center
San Francisco, California, United States, 94121
UCSF Medical Center
San Francisco, California, United States, 94121
United States, Georgia
Northside Hospital
Atlanta, Georgia, United States, 30342
United States, Indiana
Indiana Cancer Research Institute
Indianapolis, Indiana, United States, 46202
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
The Mount Sinai Hospital
New York, New York, United States, 10029
United States, Ohio
The Ohio State University
Columbus, Ohio, United States, 43210-1240
Sponsors and Collaborators
Aptose Biosciences Inc.
Ohio State University
Principal Investigator: Rebecca B Klisovic, MD Ohio State University

Responsible Party: Aptose Biosciences Inc. Identifier: NCT00565058     History of Changes
Other Study ID Numbers: 2040AML201
First Posted: November 29, 2007    Key Record Dates
Results First Posted: July 27, 2015
Last Update Posted: July 27, 2015
Last Verified: April 2015

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs