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

Acute Myeloid Leukemia Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00565058
• Other study ID #: 2040AML201
• Status: Completed
• Phase: Phase 2
• First received: November 27, 2007
• Last updated: June 29, 2015
• Start date: August 2007
• Est. completion date: February 2010

Study information

• Verified date: April 2015
• Source: Aptose Biosciences Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: February 2010
• Est. primary completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

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

Locations

Country	Name	City	State
United States	Northside Hospital	Atlanta	Georgia
United States	Roswell Park Cancer Institute	Buffalo	New York
United States	The Ohio State University	Columbus	Ohio
United States	Indiana Cancer Research Institute	Indianapolis	Indiana
United States	The Mount Sinai Hospital	New York	New York
United States	San Francisco Veterans Affairs Medical Center	San Francisco	California
United States	UCSF Medical Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Aptose Biosciences Inc.	Ohio State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Response Rate of GTI-2040 Combined With HiDAC in Refractory or Relapsed AML	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.	at 29-35 days	No
Secondary	Summary of Treatment Emergent Adverse Events	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.	30 days after the last dose	Yes