A Pharmacokinetic and Efficacy Study of Amonafide L-malate (AS1413) in Combination With Cytarabine in Patients With Acute Myeloid Leukemia (AML)

A Phase IIa Pharmacokinetic and Efficacy Study of Amonafide L-malate (AS1413) in Combination With Cytarabine in Adult Patients With Acute Myeloid Leukemia (AML)

A phase IIa study to evaluate the pharmacokinetic and efficacy of amonafide L-malate (AS1413) in combination with cytarabine in treating patients with acute myeloid leukemia (AML)

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Drug: Amonafide + cytarabine

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia, 0186
    • Medulla - Chemotherapy and Immunotherapy Clinic
  • Tbilisi, Georgia, 0177
    • Institute of Haematology and Transfusiology
  • Tbilisi, Georgia
    • Hema - Haematology and Chemotherapy Clinic
• Ukraine
  • Donetsk, Ukraine, 83045
    • Institure of URgent adn Recovery Surgery n.a. V.K. gusaka of Academy Medical Science of Ukraine
  • Kiev, Ukraine, 03115
    • Kyiv bone Marrow Transplantation Centre
  • Vinnytsya, Ukraine, 21018
    • Vinnytsya Regional Clinical Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Willing and able to provide written informed consent
2. In the opinion of the Investigator able to comply with the study assessments and follow-up
3. New diagnosis of AML (i.e. >20 % blasts) as defined by the World Health Organization (WHO) classification (Vardiman 2009) or relapsed or refractory AML as defined by the persistence or recurrence of >5% blasts in bone marrow or peripheral blood following treatment.
4. ECOG Performance status ≤ 2
5. Age > 18 years and ≤ 70 years

6. Adequate hepatic function as evidenced by the following laboratory tests:

   1. Total serum bilirubin ≤ 1.5 x ULN or direct (conjugated) bilirubin ≤ 1.5 ULN unless attributable to suspected hepatic involvement with AML
   2. Serum AST and ALT ≤ 1.5 x ULN unless attributable to suspected hepatic involvement with AML
7. Adequate renal function as evidenced by serum creatinine ≤ 1.5 x ULN
8. Women of childbearing potential must have a negative serum pregnancy test. A woman of childbearing potential is defined as one who is biologically capable of becoming pregnant. This includes women who are using contraceptives or whose sexual partners are either sterile or using contraceptives
9. Left Ventricular Ejection Fraction (LVEF) > 50%, as determined by multiplegated acquisition scan (MUGA) or echocardiogram (ECHO) within 28 days prior to administration of 1st dose of remission induction chemotherapy

Exclusion Criteria:

1. Unwilling to accept the required per protocol blood and urine sample collection
2. An initial diagnosis of acute promyelocytic leukemia as defined by French- American-British criteria (Bennett 1976) (otherwise known as FAB M3)
3. Clinically active CNS leukemia
4. History of clinically significant allergic reactions attributed to compounds of similar chemical or biological composition to amonafide or cytarabine
5. Pregnant or breast feeding
6. Known HIV positive
7. Known active hepatitis B or C, or any other active liver disease
8. Evidence of pulmonary infection. Patients with evidence of pulmonary infection on screening chest x-ray should have chest computed tomography (CT) prior to starting remission induction therapy to confirm absence or presence of pulmonary infection.
9. Any major surgery or radiation therapy within 30 days prior to study entry
10. Previously received treatment with amonafide
11. Treatment with other investigational agents for any reason within 30 days prior to study entry
12. Prior remission induction therapy for AML within 30 days of starting amonafide therapy
13. Persistent non-hematologic toxicity (other than alopecia) greater than Grade 2 from prior therapy for MDS or AML
14. Serious concomitant illnesses (for example, unstable angina or myocardial infarction or stroke within 3 months prior to study entry, congestive heart

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Single-arm; Amonafide 600 mg/m2 IV over 4 hours daily on days 1-5 in combination with cytarabine 200 mg/m2 IV continuous infusion (CI) daily on days 1-7	Drug: Amonafide + cytarabine; Amonafide 600 mg/m2 IV over 4 hours daily on days 1-5 in combination with cytarabine 200 mg/m2 IV continuous infusion (CI) daily on days 1-7

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To define the plasma PK Profile of amonafide and metabolite(s)	1 year
To deine the urniary excretion of amonafide and metabolite(s)	1 year
To investigate the fecal excretion of amonafide and metabolite(s) in selected patients	1 year
To evaluate the safety and tolerability of amonafide in combination with cytarabine	1 year
To evaluate the remission rate	1 year

Secondary Outcome Measures

Outcome Measure	Time Frame
All outcomes are of equal weighting	1 year

Collaborators and Investigators

• Sponsor: Antisoma Research

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (ANTICIPATED): September 1, 2010
• Study Completion (ANTICIPATED): January 1, 2011

Study Registration Dates

• First Submitted: February 9, 2010
• First Submitted That Met QC Criteria: February 9, 2010
• First Posted (ESTIMATE): February 10, 2010

Study Record Updates

• Last Update Posted (ESTIMATE): January 17, 2011
• Last Update Submitted That Met QC Criteria: January 14, 2011
• Last Verified: January 1, 2011

More Information

Terms related to this study

• Keywords: AML; Pgp; MDR; sAML; AS1413; Amonafide
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Cytarabine; Amonafide
• Other Study ID Numbers: AS1413-C-101