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

This study has been completed.
Sponsor:
Collaborator:
Ohio State University
Information provided by:
Aptose Biosciences Inc.
ClinicalTrials.gov Identifier:
NCT00565058
First received: November 27, 2007
Last updated: February 11, 2010
Last verified: February 2010
  Purpose

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 Intervention Phase
Acute Myeloid Leukemia
Biological: GTI-2040
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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)

Resource links provided by NLM:


Further study details as provided by Aptose Biosciences Inc.:

Primary Outcome Measures:
  • To determine the overall response rate of GTI-2040 combined with HiDAC in refractory or relapsed AML [ Time Frame: at 29-35 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the influence of GTI-2040 treatment on pharmacologic activity in leukemic cells. To assess the activity and toxicity profile of the early and delayed GTI-2040 treatment [ Time Frame: from day 0 to day 35 ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: August 2007
Study Completion Date: February 2010
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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 CR will be permitted to receive one cycle of consolidation of GTI-2040 and HiDAC

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  • 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.

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 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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00565058

Locations
United States, California
Dan Francisco Veterans Affairs Medical Center
San Francisco, California, United States
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
Investigators
Principal Investigator: Rebecca B Klisovic, MD Ohio State University
  More Information

No publications provided

Responsible Party: Peter Murray/Director, Clinical Development, Lorus Therapeutics
ClinicalTrials.gov Identifier: NCT00565058     History of Changes
Other Study ID Numbers: 2040AML201
Study First Received: November 27, 2007
Last Updated: February 11, 2010
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type

ClinicalTrials.gov processed this record on November 24, 2014